WorldWideScience

Sample records for cell cancer risk

  1. Epidemiologic characteristics and risk factors for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Loren Lipworth

    2009-04-01

    Full Text Available Loren Lipworth1,2, Robert E Tarone1,2, Lars Lund2,3, Joseph K McLaughlin1,21International Epidemiology Institute, Rockville, MD, USA; 2Department of Medicine (JKM, RET and Preventive Medicine (LL, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 3Department of Urology, Viborg Hospital, Viborg, DenmarkAbstract: Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches

  2. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    International Nuclear Information System (INIS)

    Riaz, Muhammad; Elstrodt, Fons; Hollestelle, Antoinette; Dehghan, Abbas; Klijn, Jan GM; Schutte, Mieke

    2009-01-01

    Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines

  3. Epithelial cells in nipple aspirate fluid and subsequent breast cancer risk: A historic prospective study

    International Nuclear Information System (INIS)

    Baltzell, Kimberly A; Moghadassi, Michelle; Rice, Terri; Sison, Jennette D; Wrensch, Margaret

    2008-01-01

    Past studies have shown that women with abnormal cytology or epithelial cells in nipple aspirate fluid (NAF) have an increased relative risk (RR) of breast cancer when compared to women from whom NAF was attempted but not obtained (non-yielders). This study analyzed NAF results from a group of women seen in a breast clinic between 1970–1991 (N = 2480). Our analysis presented here is an aggregate of two sub-groups: women with questionnaire data (n = 712) and those with NAF visits beginning in 1988 (n = 238), the year in which cancer case information was uniformly collected in California. Cytological classification was determined for a group of 946 women using the most abnormal epithelial cytology observed in fluid specimens. Breast cancer incidence and mortality status was determined through June 2006 using data from the California Cancer Registry, California Vital Statistics and self-report. We estimated odd ratios (ORs) for breast cancer using logistic regression analysis, adjusting for age. We analyzed breast cancer risk related to abnormality of NAF cytology using non-yielders as the referent group and breast cancer risk related to the presence or absence of epithelial cells in NAF, using non-yielders/fluid without epithelial cells as the referent group. Overall, 10% (93) of the 946 women developed breast cancer during the follow-up period. Age-adjusted ORs and 95% confidence intervals (C.I.) compared to non-yielders were 1.4 (0.3 to 6.4), 1.7 (0.9 to 3.5), and 2.0 (1.1 to 3.6) for women with fluid without epithelial cells, normal epithelial cells and hyperplasia/atypia, respectively. Comparing the presence or absence of epithelial cells in NAF, women with epithelial cells present in NAF were more likely to develop breast cancer than non-yielders or women with fluid without epithelial cells (RR = 1.9, 1.2 to 3.1). These results support previous findings that 1) women with abnormal epithelial cells in NAF have an increased risk of breast cancer when compared to

  4. Family history of skin cancer is associated with increased risk of cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Asgari, Maryam M; Warton, E Margaret; Whittemore, Alice S

    2015-04-01

    The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified. To examine the association between self-reported family history of skin cancer and SCC risk. Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors. Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6). Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

  5. Obesity and Cancer Risk

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... hormone therapy and for tumors that express hormone receptors . Obesity is also a risk factor for breast ...

  6. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci.

    Science.gov (United States)

    Coetzee, Simon G; Shen, Howard C; Hazelett, Dennis J; Lawrenson, Kate; Kuchenbaecker, Karoline; Tyrer, Jonathan; Rhie, Suhn K; Levanon, Keren; Karst, Alison; Drapkin, Ronny; Ramus, Susan J; Couch, Fergus J; Offit, Kenneth; Chenevix-Trench, Georgia; Monteiro, Alvaro N A; Antoniou, Antonis; Freedman, Matthew; Coetzee, Gerhard A; Pharoah, Paul D P; Noushmehr, Houtan; Gayther, Simon A

    2015-07-01

    Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Birth order, sibship size, and risk for germ-cell testicular cancer.

    Science.gov (United States)

    Richiardi, Lorenzo; Akre, Olof; Lambe, Mats; Granath, Fredrik; Montgomery, Scott M; Ekbom, Anders

    2004-05-01

    Several studies have reported an inverse association between birth order and testicular cancer risk, but estimates vary greatly and the biologic mechanism underlying the association is not established. We have evaluated the effect of birth order, sibship size, and the combined effect of these 2 variables in relation to risk for testicular cancer in a large, nested case-control study. Specifically, we compared 3051 patients with germ-cell testicular cancer (diagnosed between 1958 and 1998 and identified through the Swedish Cancer Registry) with 9007 population control subjects. Using record linkage with the Multi-Generation Register and the Census, we obtained information on number, order, and sex of the subjects' siblings, parental age, and paternal socioeconomic status. Both birth order and sibship size had an inverse and monotonically decreasing association with testicular cancer risk after adjusting for parental age, paternal socioeconomic status, and twin status. The associations were modified by subjects' cohort of birth and were not present among those born after 1959. The odds ratio for having at least 3 siblings, compared with none, was 0.63 (95% confidence interval = 0.53-0.75) among subjects born before 1960. Stratified analyses showed that birth order and number of younger siblings had a similar inverse association with the risk for testicular cancer. Sibship size, and not only birth order, is associated with testicular cancer risk. This suggests a higher prevalence of parental subfertility among patients with testicular cancer.

  8. Cancer risks related to low-level RF/MW exposures, including cell phones.

    Science.gov (United States)

    Szmigielski, Stanislaw

    2013-09-01

    For years, radiofrequency (RF) and microwave (MW) radiations have been applied in the modern world. The rapidly increasing use of cellular phones called recent attention to the possible health risks of RF/MW exposures. In 2011, a group of international experts organized by IARC (International Agency for Research on Cancer in Lyon) concluded that RF/MW radiations should be listed as a possible carcinogen (group 2B) for humans. Three meta-analyses of case-control studies have concluded that using cell phones for more than ten years was associated with an increase in the overall risk of developing a brain tumor. The Interphone Study, the largest health-related case-control international study of use of cell phones and head and neck tumors, showed no statistically significant increases in brain cancers related to higher amounts of cell phone use, but excess risk in a small subgroup of more heavily exposed users associated with latency and laterality was reported. So far, the published studies do not show that mobile phones could for sure increase the risk of cancer. This conclusion is based on the lack of a solid biological mechanism, and the fact that brain cancer rates are not going up significantly. However, all of the studies so far have weaknesses, which make it impossible to entirely rule out a risk. Mobile phones are still a new technology and there is little evidence about effects of long-term use. For this reason, bioelectromagnetic experts advise application of a precautionary resources. It suggests that if people want to use a cell phone, they can choose to minimize their exposure by keeping calls short and preferably using hand-held sets. It also advises discouraging children from making non essential calls as well as also keeping their calls short.

  9. Screening frequency and atypical cells and the prediction of cervical cancer risk.

    Science.gov (United States)

    Chen, Yun-Yuan; You, San-Lin; Koong, Shin-Lan; Liu, Jessica; Chen, Chi-An; Chen, Chien-Jen

    2014-05-01

    To evaluate the screening efficacy and importance of atypical squamous cells and atypical glandular cells in predicting subsequent cervical cancer risk. This national cohort study in Taiwan analyzed associations between Pap test screening frequency and findings in 1995-2000 and subsequent risk of squamous cell carcinoma and adenocarcinoma after 2002. Women aged 30 years or older in 1995 without a cervical cancer history were included. Multivariate-adjusted hazard ratios and their 95% confidence intervals (CIs) were assessed using Cox regression analysis. During a total follow-up of 31,693,980 person-years in 2002-2008, 9,471 squamous cell carcinoma and 1,455 adenocarcinoma cases were newly diagnosed, resulting in 2,067 deaths. The risk of developing and dying from squamous cell carcinoma decreased significantly with increasing attendance frequency between 1995 and 2000 (all P values for trend1995-2000 had 0.69-fold and 0.35-fold decrease in incidence and mortality of adenocarcinoma, respectively, compared with women who never attended any screenings. Abnormal cytologic findings were significant predictors of the incidence and mortality of cervical cancers. The adjusted hazard ratio (95% CI) of developing squamous cell carcinoma was 29.94 (22.83-39.25) for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions, and the adjusted hazard ratio (95% CI) of developing adenocarcinoma was 49.43 (36.49-66.97) for atypical glandular cells. Significant reductions in cervical adenocarcinoma occurred in women who attend three or more annual screenings in 6 years. High-grade atypical squamous cells and atypical glandular cells are important predictors of subsequent adenocarcinoma and squamous cell carcinoma. II.

  10. Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial.

    Science.gov (United States)

    Heaphy, Christopher M; Gaonkar, Gaurav; Peskoe, Sarah B; Joshu, Corinne E; De Marzo, Angelo M; Lucia, M Scott; Goodman, Phyllis J; Lippman, Scott M; Thompson, Ian M; Platz, Elizabeth A; Meeker, Alan K

    2015-08-01

    Telomeres are repetitive nucleoproteins that help maintain chromosomal stability by inhibiting exonucleolytic degradation, prohibiting inappropriate homologous recombination, and preventing chromosomal fusions by suppressing double-strand break signals. We recently observed that men treated for clinically localized prostate cancer with shorter telomeres in their cancer-associated stromal cells, in combination with greater variation in cancer cell telomere lengths, were significantly more likely to progress to distant metastases, and die from their disease. Here, we hypothesized that shorter stromal cell telomere length would be associated with prostate cancer risk at time of biopsy. Telomere-specific fluorescence in situ hybridization (FISH) analysis was performed in normal-appearing stromal, basal epithelial, and luminal epithelial cells in biopsies from men randomized to the placebo arm of the Prostate Cancer Prevention Trial. Prostate cancer cases (N = 32) were either detected on a biopsy performed for cause or at the end of the study per trial protocol, and controls (N = 50), defined as negative for cancer on an end-of-study biopsy performed per trial protocol (e.g., irrespective of indication), were sampled. Logistic regression was used to estimate the association between mean telomere length of the particular cell populations, cell-to-cell telomere length variability, and risk of prostate cancer. Men with short stromal cell telomere lengths (below median) had 2.66 (95% CI 1.04-3.06; P = 0.04) times the odds of prostate cancer compared with men who had longer lengths (at or above median). Conversely, we did not observe statistically significant associations for short telomere lengths in normal-appearing basal (OR = 2.15, 95% CI 0.86-5.39; P= 0 .10) or luminal (OR = 1.15, 95% CI 0.47-2.80; P = 0.77) cells. These findings suggest that telomere shortening in normal stromal cells is associated with prostate cancer risk. It is essential

  11. Reproductive History and Breast Cancer Risk

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... 4 ). This risk reduction is limited to hormone receptor –positive breast cancer; age at first full-term ...

  12. Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma

    Science.gov (United States)

    Chen, Tiantian; Cheng, Hongwei; Chen, Xingdong; Yuan, Ziyu; Yang, Xiaorong; Zhuang, Maoqiang; Lu, Ming; Jin, Li; Ye, Weimin

    2015-01-01

    A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire, and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42–2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74–36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54–2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk. PMID:26526791

  13. Skin Cancer Risk in Hematopoietic Stem-Cell Transplant Recipients Compared With Background Population and Renal Transplant Recipients

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Gniadecki, Robert; Hædersdal, Merete

    2016-01-01

    IMPORTANCE: While a high risk of nonmelanoma skin cancer is well recognized in solid-organ transplant recipients, the risk of skin cancer in hematopoietic stem-cell transplant (HSCT) recipients has not been extensively studied. OBJECTIVE: To determine the risk of cutaneous cancer in HSCT recipients...... autologous) from 1999 through 2014, 4789 RTRs from 1976 through 2014, and 10 age- and sex-matched nontransplanted individuals for each of the groups from the background population. Person-years at risk were calculated from the time of study inclusion until first cutaneous cancer. To compare the risk of skin...... cancer between transplant recipients and background population, we used a stratified proportional hazard regression model for hazard ratio (HR) estimations. By use of the cumulative incidence, we estimated 5- and 10-year risks of skin cancers. All RTR and HSCT recipients were treated and followed up...

  14. Plasma testosterone in the general population, cancer prognosis and cancer risk

    DEFF Research Database (Denmark)

    Orsted, D D; Nordestgaard, B G; Bojesen, S E

    2014-01-01

    BACKGROUND: Testosterone is an important anabolic hormone in humans and in vitro testosterone stimulates growth of lung and colon cancer cells. We tested the hypothesis that plasma testosterone associate with increased risk of cancer and with increased risk of early death after cancer. MATERIALS...

  15. Cancer stem cell marker Musashi-1 rs2522137 genotype is associated with an increased risk of lung cancer.

    Directory of Open Access Journals (Sweden)

    Xu Wang

    Full Text Available Gene single nucleotide polymorphisms (SNPs have been extensively studied in association with development and prognosis of various malignancies. However, the potential role of genetic polymorphisms of cancer stem cell (CSC marker genes with respect to cancer risk has not been examined. We conducted a case-control study involving a total of 1000 subjects (500 lung cancer patients and 500 age-matched cancer-free controls from northeastern China. Lung cancer risk was analyzed in a logistic regression model in association with genotypes of four lung CSC marker genes (CD133, ALDH1, Musashi-1, and EpCAM. Using univariate analysis, the Musashi-1 rs2522137 GG genotype was found to be associated with a higher incidence of lung cancer compared with the TT genotype. No significant associations were observed for gene variants of CD133, ALDH1, or EpCAM. In multivariate analysis, Musashi-1 rs2522137 was still significantly associated with lung cancer when environmental and lifestyle factors were incorporated in the model, including lower BMI; family history of cancer; prior diagnosis of chronic obstructive pulmonary disease, pneumonia, or pulmonary tuberculosis; occupational exposure to pesticide; occupational exposure to gasoline or diesel fuel; heavier smoking; and exposure to heavy cooking emissions. The value of the area under the receiver-operating characteristic (ROC curve (AUC was 0.7686. To our knowledge, this is the first report to show an association between a Musashi-1 genotype and lung cancer risk. Further, the prediction model in this study may be useful in determining individuals with high risk of lung cancer.

  16. Risk of skin cancer in HIV-infected patients

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Ahlström, Magnus Glinvad; Gerstoft, Jan

    2018-01-01

    BACKGROUND: The risk of skin cancer in HIV-infected patients has not been extensively studied. OBJECTIVE: To determine the risk of skin cancer in HIV-infected patients and compare it with the risk in the background population. METHODS: In a matched, nationwide population-based cohort study we...... compared the risk of skin cancer in 4280 HIV-infected patients from the Danish HIV cohort study with a background population cohort, according to the level of immunosuppression and route of transmission. Primary outcomes were time to first basal cell carcinoma (BCC), squamous cell carcinoma (SCC...

  17. Comprehensive evaluation of one-carbon metabolism pathway gene variants and renal cell cancer risk.

    Directory of Open Access Journals (Sweden)

    Todd M Gibson

    Full Text Available Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer.Tag single nucleotide polymorphisms (SNPs selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS and the closely associated glutathione synthesis pathway (CTH, GGH, GSS were genotyped for 777 renal cell carcinoma (RCC cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163 with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes.The strongest associations with RCC risk were observed for SLC19A1 (P(min-P = 0.03 and MTHFR (P(min-P = 0.13. A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785 was associated with a 37% increased risk (p = 0.02, and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake.To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings.

  18. Association between polymorphisms in pre-miRNA genes and risk of oral squamous cell cancer in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Enjiao Zhang

    Full Text Available MicroRNAs play important roles in the development of human cancers. This case-control study is to evaluate the roles of the polymorphisms in pre-miRNAs on risk of oral cancer in a Chinese population.The genotypes of three polymorphisms were determined in 340 patients with oral squamous cell cancer and 340 healthy controls who were frequency matched for age and sex. Odds ratios (ORs and 95% confidence intervals (95%CIs were calculated to assess the association. All analyses were performed using the SPSS software. 3.154( 0.001.For miR-499 rs3746444, individuals carrying homozygous CC genotype had increased risks of oral cancer compared with the homozygous wild TT genotype (adjusted OR was 3.154, 95%CI was 1.555-6.397, P value was 0.001. The C allele of miR-499 rs3746444 was associated with a higher risk of oral cancer with significant odds ratio of 1.453. In the stratified analyses by sex, the associations between miR-499 rs3746444 and miR-146a rs2910164 polymorphisms with the susceptibility of oral squamous cell cancer were significant in males. However, with 1/4 as many subjects there were no significant associations between the three polymorphisms and oral cancer risks in females. The joint effects of miRNA polymorphisms and smoking on the risk of OSCC were analyzed and the results suggested that the association between microRNA genetic variants and OSCC risk was modified by smoking.These findings suggest that miR-499 rs3746444 and miR-146a rs2910164 polymorphisms may contribute to genetic susceptibility to oral squamous cell cancer.

  19. Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.

    Science.gov (United States)

    Wentzensen, Nicolas; Poole, Elizabeth M; Trabert, Britton; White, Emily; Arslan, Alan A; Patel, Alpa V; Setiawan, V Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A; Buring, Julie; Butler, Lesley M; Chamosa, Saioa; Clendenen, Tess V; Dossus, Laure; Fortner, Renee; Gapstur, Susan M; Gaudet, Mia M; Gram, Inger T; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V; Lee, I-Min; Lundin, Eva; Merritt, Melissa A; Onland-Moret, N Charlotte; Peters, Ulrike; Poynter, Jenny N; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P; Schairer, Catherine; Schouten, Leo J; Sjöholm, Louise K; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S

    2016-08-20

    An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. © 2016 by American Society of Clinical Oncology.

  20. HIV tropism and decreased risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Nancy A Hessol

    2010-12-01

    Full Text Available During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR and 95% confidence intervals (CI for breast cancer were estimated by exact conditional logistic regression. Two (9% of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28% of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84 and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83. Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.Low breast cancer risk with HIV is specifically linked

  1. Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk

    DEFF Research Database (Denmark)

    Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A

    2009-01-01

    Polymorphisms in genes critical to cell cycle control are outstanding candidates for association with ovarian cancer risk; numerous genes have been interrogated by multiple research groups using differing tagging single-nucleotide polymorphism (SNP) sets. To maximize information gleaned from......, and rs3212891; CDK2 rs2069391, rs2069414, and rs17528736; and CCNE1 rs3218036. These results exemplify the utility of imputation in candidate gene studies and lend evidence to a role of cell cycle genes in ovarian cancer etiology, suggest a reduced set of SNPs to target in additional cases and controls....

  2. T Cells in Gastric Cancer: Friends or Foes

    Science.gov (United States)

    Amedei, Amedeo; Della Bella, Chiara; Silvestri, Elena; Prisco, Domenico; D'Elios, Mario M.

    2012-01-01

    Gastric cancer is the second cause of cancer-related deaths worldwide. Helicobacter pylori is the major risk factor for gastric cancer. As for any type of cancer, T cells are crucial for recognition and elimination of gastric tumor cells. Unfortunately T cells, instead of protecting from the onset of cancer, can contribute to oncogenesis. Herein we review the different types, “friend or foe”, of T-cell response in gastric cancer. PMID:22693525

  3. Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Allen, N.E.; Appleby, P.N.; Key, T.J.; Bueno-De-Mesquita, H.B.; Ros, M.M.; Kiemeney, L.A.L.M.; Tjonneland, A.; Roswall, N.; Overvad, K.; Weikert, S.; Boeing, H.; Chang-Claude, J.; Teucher, B.; Panico, S.; Sacerdote, C.; Tumino, R.; Palli, D.; Sieri, S.; Peeters, P.; Quiros, J.R.; Jakszyn, P.; Molina-Montes, E.; Chirlaque, M.D.; Ardanaz, E.; Dorronsoro, M.; Khaw, K.T.; Wareham, N.; Ljungberg, B; Hallmans, G.; Ehrnstrom, R.; Ericson, U.; Gram, I.T.; Parr, C.L.; Trichopoulou, A.; Karapetyan, T.; Dilis, V.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Fagherrazzi, G.; Romieu, I.; Gunter, M.J.; Riboli, E.

    2013-01-01

    Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations

  4. Prevalence of micronuclei in exfoliated uterine cervical cells from patients with risk factors for cervical cancer.

    Science.gov (United States)

    Reis Campos, Lízia Maria Franco dos; Luz Dias, Francisca da; Antunes, Lusânia Maria Greggi; Murta, Eddie Fernando Candido

    2008-11-01

    Pap smears are the most common and inexpensive screening method for cervical cancer. We analyzed micronucleus prevalence in exfoliated cervical mucosa cells, to investigate associations between increased numbers of micronuclei and risk factors for cervical cancer. Analytical cross-sectional study, at Instituto de Pesquisa em Oncologia (IPON). Exfoliated cervical cells were obtained from 101 patients between September 2004 and November 2005. Patients' ages, habits (passive or active smoking, alcoholism and numbers of sexual partners), age at first sexual intercourse, contraceptive methods used, histories of sexually transmitted diseases, use of hormone replacement therapy, numbers of pregnancies and abortions, inflammatory cytology and cervical intraepithelial neoplasia (CIN) were obtained. Cells were collected using Ayre spatulas, transferred to vials containing 0.9% saline solution for micronucleus tests and analyzed at 1000x magnification. The number of micronuclei in 1,000 epithelial cells per patient sample was counted. Comparisons between groups with active (7.9 +/- 7.8) and passive (7.2 +/- 10.6) smoking versus no smoking (3.7 +/- 5.1); with/without alcoholism (7.8 +/- 1.4 and 6.9 +/- 10.1); with/without inflammatory cytology (10.7 +/- 10.5 and 1.3 +/- 1.7); and with CIN I, II and III and no CIN (respectively 4.3 +/- 4.3, 10.6 +/- 5.3, 22.7 +/- 11.9 and 1.3 +/- 1.4) found elevated micronucleus prevalence (P < 0.05). We concluded that the prevalence of micronuclei in exfoliated uterine cervical cells was greater in patients with one or more risk factors for uterine cervical cancer than in patients without risk factors.

  5. Cytokine single-nucleotide polymorphisms and risk of non-small-cell lung cancer.

    Science.gov (United States)

    Pérez-Ramírez, Cristina; Alnatsha, Ahmed; Cañadas-Garre, Marisa; Villar, Eduardo; Valdivia-Bautista, Javier; Faus-Dáder, María J; Calleja-Hernández, Miguel Á

    2017-12-01

    Lung cancer, particularly the non-small-cell lung cancer (NSCLC) subtype, is the leading cause of cancer-related death worldwide. Several functional polymorphisms in inflammatory cytokine genes, such as IL1B, IL6, IL12A, IL13 and IL16, have been associated with the risk of NSCLC. The aim of this study was to evaluate the association between ILs gene polymorphisms and the risk of developing NSCLC. A retrospective case-control study was carried out, including 174 NSCLC cases and 298 controls of Spanish origin. IL1B (rs1143634), IL1B (rs12621220), IL1B (rs1143623), IL1B (rs16944), IL1B (rs1143627), IL12A (rs662959), IL13 (rs1881457), IL6 (rs1800795) and IL16 (rs7170924) gene polymorphisms were analysed by TaqMan. The genotypic logistic regression model adjusted by smoking status showed that the IL1B rs1143634-TT genotype was associated with a lower risk of NSCLC (P=0.04312; odds ratio=0.226; 95% confidence interval=0.044-0.840). No other gene polymorphisms showed an association with NSCLC in any of the models tested. In conclusion, IL1B rs1143634 was significantly associated with a higher risk of NSCLC. No influence of IL1B rs12621220, rs1143623, rs16944, rs1143627, IL12A rs662959, IL13 rs1881457 and IL16 rs7170924 on the risk of developing NSCLC was found in our study.

  6. Statin use and risk of nonmelanoma skin cancer

    DEFF Research Database (Denmark)

    Pedersen, Sidsel Arnspang; Pottegård, A; Friis, S

    2015-01-01

    Background:Evidence is conflicting regarding statin use and risk of basal cell (BCC) and squamous cell skin cancer (SCC).Methods:Using Danish nationwide registries, we identified all patients with incident BCC/SCC during 2005-2009 and matched them to population controls. We computed odds ratios...... plausibly explains the marginally increased risk of BCC.British Journal of Cancer advance online publication, 7 October 2014; doi:10.1038/bjc.2014.527 www.bjcancer.com....

  7. Epithelial cell proliferative activity of Barrett's esophagus : methodology and correlation with traditional cancer risk markers

    NARCIS (Netherlands)

    Peters, FTM; Ganesh, S; Kuipers, EJ; De Jager-Krikken, A; Karrenbeld, A; Harms, Geert; Sluiter, WJ; Koudstaal, J; Klinkenberg-Knol, EC; Lamers, CBHW; Kleibeuker, JH

    Barrett's esophagus (BE) is a premalignant condition, due to chronic gastroesophageal reflux. Effective antireflux therapy may diminish cancer risk. To evaluate this option an intermediate marker is needed. We developed a methodology for measurement of epithelial cell proliferative activity of

  8. Exposure to low levels of ionizing radiation and lung cancer risk in Florida

    International Nuclear Information System (INIS)

    Stockwell, H.G.; Lyman, G.H.; Waltz, J.

    1986-01-01

    The phosphate deposits of central Florida contain levels of uranium and its daughter products 30-60 times greater than average soils. A case-control study was conducted to assess the risk of lung cancer associated with living on these phosphateic soils. Using the records of the state-wide Florida Cancer Data System to address this issue, all cases of lung cancer among Florida residents in 1981 were identified (n = 7049). Information was obtained regarding residence, age, sex, race, and smoking habits. Controls consisted of 6643 individuals with cancers of the colon or rectum. Residents of the central Florida phosphate region experienced a significant increase in lung cancer risk compared to other Florida residents (odds ratio (OR) = 1.4). Excess risks appeared concentrated among squamous cell cancer (OR = 1.6) and small cell cancer (OR = 1.6). When smoking habits as well as residential area was considered, no significant excess risk, associated with residence, was observed among nonsmokers or light smokers. Area residents smoking a pack or more per day experienced a 70% increase in lung cancer risk compared to individuals smoking a similar amount but living elsewhere. Highest risks were observed among persons with squamous cell cancer (OR = 2.1) and small cell cancer (OR = 2.5) who smoked more than 40 cigarettes a day. Results suggest exposure to low levels of ionizing radiation increases the lung cancer risk of residents of this area

  9. Risk of cancer formation by radiotherapy

    International Nuclear Information System (INIS)

    Fuji, Hiroshi

    2011-01-01

    Described are the difference between exposures to radiation for medical purpose and to environmental radiation at low dose, estimation of carcinogenic risk by medical radiation, and notice for referring the risk at clinical practice. ICRP employs linear non-threshold (LNT) model for risk of cancer formation even at <200 mSv for safety, with a recognition that it is scientifically obscure. The model essentially stands on data of A-bomb survivors (the Gold Standard), where the relationship between 5-10% excess relative risk (ERR) of cancer formation and dose 0.05-2.5 Sv is linear. Analyses of the secondary carcinogenesis after radiotherapy have begun to be reported since around 2005: e.g., the secondary thyroid cancer risk in pediatric patients treated with radiotherapy has a peak at 20 Gy, suggesting the actual risk depends both on the linearity of carcinogenic increase and on the exponential probability of cell death increase. On this concept, the risk of cancer formation is not always linear to dose. At the practical radiotherapy, its secondary carcinogenic risk should be estimated not only on the dose but also on other factors such as the individual organ, patient's age and attainable age/time after the treatment. In treated teen-ager patients, ERRs of mortality/Gy are 2.28 for cancers of the skin of non-malignant melanoma, 1.32 of bladder and 1.21 of thyroid and in patients of fifties, 1.15 of bladder and lung. The EER tends to become lower as the treated age is older. Pediatric cancer patients to be treated with radiotherapy should be informed about the secondary cancer that the low dose risk given by ICRP is not always appropriate, a certain cancer risk has a peak dose, and ERR of cancer mortality is not a cancer risk of an organ. Many factors like anticancers and immuno-modifiers, modify the outcome of radiotherapy and should be carefully speculated for evaluating the outcome. (T.T.)

  10. Low dose diagnostic radiation does not increase cancer risk in cancer prone mice

    Energy Technology Data Exchange (ETDEWEB)

    Boreham, D., E-mail: dboreham@nosm.ca [Northern Ontario School of Medicine, ON (Canada); Phan, N., E-mail: nghiphan13@yahoo.com [Univ. of Ottawa, Ottawa, ON (Canada); Lemon, J., E-mail: lemonja@mcmaster.ca [McMaster Univ., Hamilton, ON (Canada)

    2014-07-01

    The increased exposure of patients to low dose diagnostic ionizing radiation has created concern that these procedures will result in greater risk of carcinogenesis. However, there is substantial evidence that shows in many cases that low dose exposure has the opposite effect. We have investigated whether CT scans can modify mechanisms associated with carcinogenesis in cancer-prone mice. Cancer was induced in Trp53+/- mice with an acute high dose whole-body 4 Gy γ-radiation exposure. Four weeks following the cancer-inducing dose, weekly whole-body CT scans (10 mGy/scan, 75 kVp X-rays) were given for ten consecutive weeks adding an additional radiation burden of 0.1 Gy. Short-term biological responses and subsequent lifetime cancer risk were investigated. Five days following the last CT scan, there were no detectable differences in the spontaneous levels of DNA damage in blood cells (reticulocytes). In fact, CT scanned mice had significantly lower constitutive levels of oxidative DNA damage and cell death (apoptosis), compared to non-CT scanned mice. This shows that multiple low dose radiation exposures modified the radio response and indicates protective processes were induced in mice. In mice treated with the multiple CT scans following the high cancer-inducing 4 Gy dose, tumour latency was increased, significantly prolonging lifespan. We conclude that repeated CT scans can reduce the cancer risk of a prior high-dose radiation exposure, and delay the progression of specific types of radiation-induced cancers in Trp53+/-mice. This research shows for the first time that low dose exposure long after cancer initiation events alter risk and reduce cancer morbidity. Cancer induction following low doses does not follow a linear non-threshold model of risk and this model should not be used to extrapolate risk to humans following low dose exposure to ionizing radiation. (author)

  11. Risk of skin cancer following tamoxifen treatment in more than 16,000 breast cancer patients

    DEFF Research Database (Denmark)

    Præstegaard, Camilla; Kjaer, Susanne K.; Andersson, Michael

    2016-01-01

    Background: Women with breast cancer are at increased risk of developing skin cancer. Little is known about how tamoxifen affects this risk. We aimed to investigate whether tamoxifen treatment following breast cancer is associated with skin cancer. Methods: A cohort consisting of 44,589 women...... diagnosed with breast cancer during 1977–2007 from the nationwide clinical database of the Danish Breast Cancer Cooperative Group, was followed for a primary skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or melanoma] in the Danish Cancer Registry supplemented by data on BCC and SCC...... from the Danish Pathology Register. We investigated incidence of skin cancer among 16,214 women treated with tamoxifen compared to 28,375 women not treated with tamoxifen by calculating incidence rate ratios (IRRs) in Cox regression models. Results: Tamoxifen users were followed for a median of 2...

  12. Prevalence of micronuclei in exfoliated uterine cervical cells from patients with risk factors for cervical cancer

    Directory of Open Access Journals (Sweden)

    Lízia Maria Franco dos Reis Campos

    Full Text Available CONTEXT AND OBJECTIVE: Pap smears are the most common and inexpensive screening method for cervical cancer. We analyzed micronucleus prevalence in exfoliated cervical mucosa cells, to investigate associations between increased numbers of micronuclei and risk factors for cervical cancer. DESIGN AND SETTING: Analytical cross-sectional study, at Instituto de Pesquisa em Oncologia (IPON. METHODS: Exfoliated cervical cells were obtained from 101 patients between September 2004 and November 2005. Patients' ages, habits (passive or active smoking, alcoholism and numbers of sexual partners, age at first sexual intercourse, contraceptive methods used, histories of sexually transmitted diseases, use of hormone replacement therapy, numbers of pregnancies and abortions, inflammatory cytology and cervical intraepithelial neoplasia (CIN were obtained. Cells were collected using Ayre spatulas, transferred to vials containing 0.9% saline solution for micronucleus tests and analyzed at 1000x magnification. The number of micronuclei in 1,000 epithelial cells per patient sample was counted. RESULTS: Comparisons between groups with active (7.9 ± 7.8 and passive (7.2 ± 10.6 smoking versus no smoking (3.7 ± 5.1; with/without alcoholism (7.8 ± 1.4 and 6.9 ± 10.1; with/without inflammatory cytology (10.7 ± 10.5 and 1.3 ± 1.7; and with CIN I, II and III and no CIN (respectively 4.3 ± 4.3, 10.6 ± 5.3, 22.7 ± 11.9 and 1.3 ± 1.4 found elevated micronucleus prevalence (P < 0.05. CONCLUSIONS: We concluded that the prevalence of micronuclei in exfoliated uterine cervical cells was greater in patients with one or more risk factors for uterine cervical cancer than in patients without risk factors.

  13. Helicobacter pylori seropositivity and risk of lung cancer.

    Directory of Open Access Journals (Sweden)

    Jill Koshiol

    Full Text Available Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA antigens, we calculated odds ratios (ORs and 95% confidence intervals (95% CIs for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6 or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7. Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.

  14. Sexual activity and the risk of prostate cancer: Review article

    Directory of Open Access Journals (Sweden)

    Ahmed Fouad Kotb

    2015-09-01

    Full Text Available Introduction: Sexual activity can affect prostate cancer pathogenesis in a variety of ways; including the proposed high androgen status, risk of sexually transmitted infections and the potential effect of retained carcinogens within the prostatic cells. Methods: PubMed review of all publications concerning sexual activity and the risk of prostate cancer was done by two researchers. Results: Few publications could be detected and data were classified as a prostate cancer risk in association with either heterosexual or homosexual activities. Conclusion: Frequent ejaculation seems to be protective from the development of prostate cancer. Multiple sexual partners may be protective from prostate cancer, excluding the risk of sexually transmitted infections. Homosexual men are at a greater risk for the diagnosis of prostate cancer.

  15. Breast cancer risks and risk prediction models.

    Science.gov (United States)

    Engel, Christoph; Fischer, Christine

    2015-02-01

    BRCA1/2 mutation carriers have a considerably increased risk to develop breast and ovarian cancer. The personalized clinical management of carriers and other at-risk individuals depends on precise knowledge of the cancer risks. In this report, we give an overview of the present literature on empirical cancer risks, and we describe risk prediction models that are currently used for individual risk assessment in clinical practice. Cancer risks show large variability between studies. Breast cancer risks are at 40-87% for BRCA1 mutation carriers and 18-88% for BRCA2 mutation carriers. For ovarian cancer, the risk estimates are in the range of 22-65% for BRCA1 and 10-35% for BRCA2. The contralateral breast cancer risk is high (10-year risk after first cancer 27% for BRCA1 and 19% for BRCA2). Risk prediction models have been proposed to provide more individualized risk prediction, using additional knowledge on family history, mode of inheritance of major genes, and other genetic and non-genetic risk factors. User-friendly software tools have been developed that serve as basis for decision-making in family counseling units. In conclusion, further assessment of cancer risks and model validation is needed, ideally based on prospective cohort studies. To obtain such data, clinical management of carriers and other at-risk individuals should always be accompanied by standardized scientific documentation.

  16. Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer.

    Science.gov (United States)

    Hayes, Richard B; Ahn, Jiyoung; Fan, Xiaozhou; Peters, Brandilyn A; Ma, Yingfei; Yang, Liying; Agalliu, Ilir; Burk, Robert D; Ganly, Ian; Purdue, Mark P; Freedman, Neal D; Gapstur, Susan M; Pei, Zhiheng

    2018-03-01

    Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. To prospectively examine associations between the oral microbiome and incident HNSCC. This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant. Incident HNSCC. The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco

  17. Helicobacter pylori Diversity and Gastric Cancer Risk

    Directory of Open Access Journals (Sweden)

    Timothy L. Cover

    2016-03-01

    Full Text Available Gastric cancer is a leading cause of cancer-related death worldwide. Helicobacter pylori infection is the strongest known risk factor for this malignancy. An important goal is to identify H. pylori-infected persons at high risk for gastric cancer, so that these individuals can be targeted for therapeutic intervention. H. pylori exhibits a high level of intraspecies genetic diversity, and over the past two decades, many studies have endeavored to identify strain-specific features of H. pylori that are linked to development of gastric cancer. One of the most prominent differences among H. pylori strains is the presence or absence of a 40-kb chromosomal region known as the cag pathogenicity island (PAI. Current evidence suggests that the risk of gastric cancer is very low among persons harboring H. pylori strains that lack the cag PAI. Among persons harboring strains that contain the cag PAI, the risk of gastric cancer is shaped by a complex interplay among multiple strain-specific bacterial factors as well as host factors. This review discusses the strain-specific properties of H. pylori that correlate with increased gastric cancer risk, focusing in particular on secreted proteins and surface-exposed proteins, and describes evidence from cell culture and animal models linking these factors to gastric cancer pathogenesis. Strain-specific features of H. pylori that may account for geographic variation in gastric cancer incidence are also discussed.

  18. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Pearce, C L; Near, A M; Van Den Berg, D J

    2009-01-01

    The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had...... been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P... and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted....

  19. Factors that modify risks of radiation-induced cancer

    International Nuclear Information System (INIS)

    Fabrikant, J.I.

    1988-11-01

    The collective influence of biologic and physical factors that modify risks of radiation-induced cancer introduces uncertainties sufficient to deny precision of estimates of human cancer risk that can be calculated for low-dose radiation in exposed populations. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, minimum latent period, time-to-tumor recognition, and the influence of individual host (age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Other modifying factors include other carcinogens, and other biological sources (hormonal status, immune status, hereditary factors)

  20. How breast cancer chemotherapy increases the risk of leukemia: Thoughts about a case of diffuse large B-cell lymphoma and leukemia after breast cancer chemotherapy.

    Science.gov (United States)

    Zhang, Bin; Zhang, Xia; Li, Minghuan; Kong, Li; Deng, Xiaoqin; Yu, Jinming

    2016-01-01

    The latest studies suggest that prophylactic chemotherapy or adjuvant chemotherapy for early stage breast cancer may increase the leukemia risk in patients. For patients with a low risk for breast cancer recurrence, physicians who make the choice for adjuvant therapy should consider the risk of its long-term side effects. Is the occurrence of lymphatic system cancer and leukemia after breast cancer treatment associated with chemotherapy? Can these types of leukemia be classified as therapy-related leukaemias? We believe that there may be correlations between any diseases, butwe cannot rush to conclusions or dismiss a correlation because we understand little about the diseases themselves.In this paper, we present a case of secondary diffuse large B-cell lymphoma and leukemia in patients after breast cancer chemotherapy, it is undeniable that this is a special event. For two distinct tumouroccurrences at different times, we cannot give a clear explanation because of thechanges in the genes that might link them together and we hope to attract the attention of other clinicians.

  1. Cancer risks from ingestion of radiostrontium

    Energy Technology Data Exchange (ETDEWEB)

    Raabe, O. G.

    2004-07-01

    Studies have been conducted of the lifetime effects in 403 beagles of the skeletal uptake in seven logarithmically increasing dosage groups of ingested Sr-90. The Sr-90 was fed during skeletal developmental from mid-gestation to adulthood at age 540 days resulting in lifetime protracted beta radiation exposure of the skeleton and some adjacent tissues. Statistical analysis of all types of cancer deaths in the 403 exposed beagles and in 162 unexposed controls indicated that deaths caused by five types of cancer were significantly elevated by high level exposure to Sr-90; these were (1) myeloid leukemia, (2) bone sarcoma, (3) squamous cell carcinoma of periodontal origin, (4) nasal carcinoma, and (5) oral carcinoma. Dose response analysis of these radiation-induced cancer deaths showed non-linear relationships with marked thresholds. A mean lifetime skeletal absorbed dose of 22.5 +/-5.7 Gy SD (22.5 +/-5.7 Sv SD) was associated with the lowest dosage group in which any radiation induced cancer deaths were observed. Three-dimensional models of the observed dose-rate/time/response relationships were fir with maximum likelihood regression methods to describe the risks of death associated with the different types of radiation-induced cancer. The models show that a life-time virtual threshold for cancer risk occurs because the time required to induce cancer is longer at lower radiation dose rates and may exceed the natural life span. Scaling these results to predict human cancer risks from ingestion of Sr-90 shows negligible risks for people whose lifetime cumulative skeletal dose is less than 10 Sv. (Author)

  2. PCOS and cancer risk.

    Directory of Open Access Journals (Sweden)

    Tadeusz Issat

    2010-01-01

    Full Text Available Polycystic ovary syndrome (PCOS affects approximately 5 to 10% of women of reproductive age. It is the most common reason of anovulation in infertile women. PCOS is accompanied by such conditions as oligo- or anovulation, hipertestosteronism, lower cell sensitivity to insulin, type II diabetes, hyperlipidemia and obesity. Each of the above-mentioned conditions is an approved risk factor proved to predispose towards cancer. However, PCOS is also a disease entity which differs in its clinical manifestation. For example not all patients suffer from obesity or hipertestosteronism related symptoms. From the analysis of literature it is possible to draw conclusions, that there is a possible correlation between PCOS and endometrial cancer, which emerges from clinical trials or research focused on molecular changes in endometrium patients with PCOS. On the other hand, correlation between PCOS and breast or ovary cancer is not so strong, in spite of single papers which are showing the link. The main problem in researching the correlation between PCOS and any cancer risk, is there is a very small group of women or the trial is imperfect (e.g. no control group. There is no meta-analysis focused on this correlation in literature. The change of criteria of PCOS in the past is also a big problem, because there was a number of definitions of PCOS, which results in inconsistent PCOS diagnoses over time. In this paper we would like to provide a description of studies that aimed at showing correlation between PCOS and cancer risk and underlying theoretical assumptions.

  3. LINE-1 methylation levels in leukocyte DNA and risk of renal cell cancer.

    Directory of Open Access Journals (Sweden)

    Linda M Liao

    Full Text Available Leukocyte global DNA methylation levels are currently being considered as biomarkers of cancer susceptibility and have been associated with risk of several cancers. In this study, we aimed to examine the association between long interspersed nuclear elements (LINE-1 methylation levels, as a biomarker of global DNA methylation in blood cell DNA, and renal cell cancer risk.LINE-1 methylation of bisulfite-converted genomic DNA isolated from leukocytes was quantified by pyrosequencing measured in triplicate, and averaged across 4 CpG sites. A total of 328 RCC cases and 654 controls frequency-matched(2∶1 on age(±5years, sex and study center, from a large case-control study conducted in Central and Eastern Europe were evaluated.LINE-1 methylation levels were significantly higher in RCC cases with a median of 81.97% (interquartile range[IQR]: 80.84-83.47 compared to 81.67% (IQR: 80.35-83.03 among controls (p = 0.003, Wilcoxon. Compared to the lowest LINE-1 methylation quartile(Q1, the adjusted ORs for increasing methylation quartiles were as follows: OR(Q2 = 1.84(1.20-2.81, OR(Q3 = 1.72(1.11-2.65 and OR(Q4 = 2.06(1.34-3.17, with a p-trend = 0.004. The association was stronger among current smokers (p-trend<0.001 than former or never smokers (p-interaction = 0.03. To eliminate the possibility of selection bias among controls, the relationship between LINE-1 methylation and smoking was evaluated and confirmed in a case-only analysis, as well.Higher levels of LINE-1 methylation appear to be positively associated with RCC risk, particularly among current smokers. Further investigations using both post- and pre-diagnostic genomic DNA is warranted to confirm findings and will be necessary to determine whether the observed differences occur prior to, or as a result of carcinogenesis.

  4. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Exercise regulates breast cancer cell viability

    DEFF Research Database (Denmark)

    Dethlefsen, Christine; Lillelund, Christian; Midtgaard, Julie

    2016-01-01

    .003) and cytokines. Yet, these systemic adaptations had no effect on breast cancer cell viability in vitro. During 2 h of acute exercise, increases in serum lactate (6-fold, p ... no impact. Our data question the prevailing dogma that training-dependent baseline reductions in risk factors mediate the protective effect of exercise on breast cancer. Instead, we propose that the cancer protection is driven by accumulative effects of repeated acute exercise responses.......Purpose: Exercise decreases breast cancer risk and disease recurrence, but the underlying mechanisms are unknown. Training adaptations in systemic factors have been suggested as mediating causes. We aimed to examine if systemic adaptations to training over time, or acute exercise responses...

  6. The biologic effects of cigarette smoke on cancer cells.

    Science.gov (United States)

    Sobus, Samantha L; Warren, Graham W

    2014-12-01

    Smoking is one of the largest preventable risk factors for developing cancer, and continued smoking by cancer patients is associated with increased toxicity, recurrence, risk of second primary cancer, and mortality. Cigarette smoke (CS) contains thousands of chemicals, including many known carcinogens. The carcinogenic effects of CS are well established, but relatively little work has been done to evaluate the effects of CS on cancer cells. In this review of the literature, the authors demonstrate that CS induces a more malignant tumor phenotype by increasing proliferation, migration, invasion, and angiogenesis and by activating prosurvival cellular pathways. Significant work is needed to understand the biologic effect of CS on cancer biology, including the development of model systems and the identification of critical biologic mediators of CS-induced changes in cancer cell physiology. © 2014 American Cancer Society.

  7. Endometriosis and risks for ovarian, endometrial and breast cancers

    DEFF Research Database (Denmark)

    Mogensen, Julie Brøchner; Kjær, Susanne K.; Mellemkjær, Lene

    2016-01-01

    Objective A growing body of evidence suggests that endometriosis increases the risk for ovarian cancer, but it is less well studied whether the excess risk is confined to certain histotypes. Furthermore, it is not fully resolved if endometriosis is associated with endometrial- and breast cancer....... The aim was to study overall- and histotype-specific risks for these hormone-dependent cancers in women with endometriosis. Methods In the Danish National Patient Register, we identified 45,790 women with a clinical diagnosis of endometriosis during 1977–2012. We linked the cohort to the Danish Cancer...... Register and calculated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs). Results Endometriosis was associated with increased risks for ovarian cancer (SIR 1.34; 95% CI: 1.16–1.55), due primarily to endometrioid (SIR 1.64; 95% CI: 1.09–2.37) and clear-cell types (SIR 3...

  8. Increased colon cancer risk after severe Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Lapo Mughini-Gras

    Full Text Available Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans.We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999-2015 for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264 were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1-2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA and Statistics Netherlands (CBS allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD, and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09-2.10 among patients with Salmonella infection diagnosed <60 years of age. Such increased risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38-3.09 after S. Enteritidis infection (SIR 2.97; 95%CI 1.73-4.76. Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade

  9. Are twins at risk of cancer: results from the Swedish family-cancer database.

    Science.gov (United States)

    Hemminki, Kari; Chen, Bowang

    2005-10-01

    A few twin studies on cancer have addressed questions on the possible carcinogenic or protective effects of twining by comparing the occurrence of cancer in twins and singletons. The nationwide Swedish Family-Cancer Database of 10.2 million individuals and 69,654 0- to 70-year-old twin pairs were used to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all main cancers compared to singletons. The overall risk of cancer in same- or different-sex twins was at the same level as the risk for singletons. Testicular cancer, particularly seminoma, was increased among same-sex twins (1.54) and all twins to an SIR of 1.38. Among other tumors, neurinomas and non-thyroid endocrine gland tumors were increased. Colorectal cancers and leukemia were decreased among all twins. Melanoma and squamous cell skin cancer were decreased in male same-sex twins. The data on this unselected population of twins suggest that twinning per se is not a risk factor of cancer. In utero hormonal exposures or postnatal growth stimulation may be related to the risk of testicular cancer and pituitary tumors. Protective effects against colorectal cancer may be related to a beneficial diet, and in melanoma and skin cancer, to socioeconomic factors. The study involved multiple comparisons, and internal consistency between the results was one of the main factors considered for their plausibility. The results should encourage others working on twin and singleton populations to examine the specific associations and emerging hypotheses.

  10. Increased colon cancer risk after severe Salmonella infection

    OpenAIRE

    Mughini-Gras, Lapo; Schaapveld, Michael; Kramers, Jolanda; Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

    2018-01-01

    Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-b...

  11. On ionising radiation and breast cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Mattson, Anders

    1999-05-01

    A cohort of 3,090 women with clinical diagnosis of benign breast disease (BBD) was studied. Of these, 1,216 were treated with radiation therapy during 1925-54 (median age 40 years). The mean dose to the breasts was 5.8 Gy (range 0-50 Gy). Among other organs the lung received the highest scattered dose (0.75 Gy; range 0.004-8.98 Gy) and the rectum the lowest (0.008 Gy; range 0-0.06 Gy). A pooled analysis of eight breast cancer incidence cohorts was done, including: tumour registry data on breast cancer incidence among women in the Life Span Study cohort of atomic bomb survivors; women in Massachusetts who received repeated chest fluoroscopic during lung collapse treatment for tuberculosis; women who received x-ray therapy for acute post-partum mastitis; women who were irradiated in infancy for enlarged thymus glands ; two Swedish cohorts of women who received radiation treatments during infancy for skin hemangioma; and the BBD cohort. Together the cohorts included almost 78,000 women (-35,000 were exposed), around 1.8 million woman-years and 1500 cases. The breast cancer incidence rate as a function of breast dose was analysed using linear-quadratic Poisson regression models. Cell-killing effects and other modifying effects were incorporated through additional log-linear terms. Additive (EAR) and multiplicative (ERR) models were compared in estimating the age-at-exposure patterns and time related excess. The carcinogenic risks associated with radiation in mammographic mass screening is evaluated. Assessment was made in terms of breast cancer mortality and years of life. Effects were related to rates not influenced by a mammographic mass screening program and based on a hypothetical cohort of 100,000 40-year old women with no history of breast cancer being followed to 100 years of age. Two radiation risk assumptions were compared. The dose-response relationship is linear with little support in data for an upward curvature at low to medium doses. The competing effect

  12. On ionising radiation and breast cancer risk

    International Nuclear Information System (INIS)

    Mattson, Anders

    1999-01-01

    A cohort of 3,090 women with clinical diagnosis of benign breast disease (BBD) was studied. Of these, 1,216 were treated with radiation therapy during 1925-54 (median age 40 years). The mean dose to the breasts was 5.8 Gy (range 0-50 Gy). Among other organs the lung received the highest scattered dose (0.75 Gy; range 0.004-8.98 Gy) and the rectum the lowest (0.008 Gy; range 0-0.06 Gy). A pooled analysis of eight breast cancer incidence cohorts was done, including: tumour registry data on breast cancer incidence among women in the Life Span Study cohort of atomic bomb survivors; women in Massachusetts who received repeated chest fluoroscopic during lung collapse treatment for tuberculosis; women who received x-ray therapy for acute post-partum mastitis; women who were irradiated in infancy for enlarged thymus glands ; two Swedish cohorts of women who received radiation treatments during infancy for skin hemangioma; and the BBD) cohort. Together the cohorts included almost 78,000 women (-35,000 were exposed), around 1.8 million woman-years and 1500 cases. The breast cancer incidence rate as a function of breast dose was analysed using linear-quadratic Poisson regression models. Cell-killing effects and other modifying effects were incorporated through additional log-linear terms. Additive (EAR) and multiplicative (ERR) models were compared in estimating the age-at-exposure patterns and time related excess. The carcinogenic risks associated with radiation in mammographic mass screening is evaluated. Assessment was made in terms of breast cancer mortality and years of life. Effects were related to rates not influenced by a mammographic mass screening program and based on a hypothetical cohort of 100,000 40-year old women with no history of breast cancer being followed to 100 years of age. Two radiation risk assumptions were compared. The dose-response relationship is linear with little support in data for an upward curvature at low to medium doses. The competing effect

  13. Gastric washing by distilled water can reduce free gastric cancer cells exfoliated into the stomach lumen.

    Science.gov (United States)

    Ohki, Atsuko; Abe, Nobutsugu; Yoshimoto, Eri; Hashimoto, Yoshikazu; Takeuchi, Hirohisa; Nagao, Gen; Masaki, Tadahiko; Mori, Toshiyuki; Ohkura, Yasuo; Sugiyama, Masanori

    2018-04-25

    Intragastric free cancer cells in patients with gastric cancer have rarely been studied. The purpose of this study was to investigate the detection rate of intragastric free cancer cells in gastric washes using two types of solutions during endoscopic examination. We further clarified risk factors affecting the presence of exfoliated free cancer cells. A total of 175 patients with gastric cancer were enrolled. Lactated Ringer's solution (N = 89) or distilled water (DW; N = 86) via endoscopic working channel was sprayed onto the tumor surface, and the resultant fluid was collected for cytological examination. We compared the cancer-cell positivity rate between the two (Ringer and DW) groups. We also tested the correlation between cancer-cell positivity and clinicopathological factors in the Ringer group to identify risk factors for the presence of exfoliated cancer cells. The cancer-cell positivity rate was significantly higher in the Ringer group than that in the DW group (58 vs 6%). Cytomorphology in the Ringer group was well maintained, but not in the DW group. The larger tumor size (≥ 20 mm) and positive lymphatic involvement were significant risk factors of exfoliated free cancer cells. Cancer cells can be highly exfoliated from the tumor surface into the gastric lumen by endoscopic irrigation in large gastric cancer with lymphatic involvement. Gastric washing by DW can lead to cytoclasis of free cancer cells; therefore, it may minimize the possibility of cancer-cell seeding in procedures carrying potential risks of tumor-cell seeding upon transluminal communication, such as endoscopic full-thickness resection and laparoscopy-endoscopy cooperative surgery.

  14. Endometriosis and the risk of skin cancer: a prospective cohort study.

    Science.gov (United States)

    Farland, Leslie V; Lorrain, Simon; Missmer, Stacey A; Dartois, Laureen; Cervenka, Iris; Savoye, Isabelle; Mesrine, Sylvie; Boutron-Ruault, Marie-Christine; Kvaskoff, Marina

    2017-10-01

    Endometriosis has been associated with an increased risk of skin melanoma. However, associations with other skin cancer types and how they compare with melanoma are unclear. Our objective was to prospectively investigate the relationships between endometriosis and risk of non-melanoma and melanoma skin cancers. E3N is a prospective cohort of 98,995 French women aged 40-65 years in 1990. Data on surgically confirmed endometriosis and skin cancer diagnoses were collected every 2-3 years through self-report, with skin cancer cases confirmed through pathology reports. Hazard Ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox regression models. Between 1990 and 2008, 535 melanoma, 247 squamous-cell carcinoma (SCC), and 1,712 basal-cell carcinoma (BCC) cases were ascertained. Endometriosis was associated with an increased overall risk of skin cancer (HR 1.28, 95% CI 1.05-1.55). When considering skin cancer type, endometriosis was associated with melanoma risk (HR 1.64, 95% CI 1.15-2.35), but not with SCC (HR 1.21, 95% CI 0.62-2.36) or BCC (HR 1.16, 95% CI 0.91-1.48) (non-melanoma skin cancers combined: HR 1.17, 95% CI 0.93-1.46), although no heterogeneity was detected across skin cancer types (Phomogeneity = 0.13). These data support an association between a personal history of endometriosis and the risk of skin cancer and suggest that the association is strongest for melanoma.

  15. Genetic instability model for cancer risk in A-bomb survivors

    International Nuclear Information System (INIS)

    Niwa, Ohtsura

    1998-01-01

    This review was written rather against Mendelsohn's reductionist model for cancer risk in A-bomb survivors in following chapters. Assumptions for carcinogenic process: mutation of a cell to the cancer cell and its proliferation. Multi-step theory for carcinogenesis and age of crisis: induction of cancer by accumulation of cancer-related gene mutations which being linear to time (age). Effect of exogenous hit in the multi-step theory: radiation as an exogenous hit to damage DNA. Dose-effect relationship for cancer risk in the survivors and the problem for the latent period: for solid tumors, dose-effect relationship is linear and shortening of the latent period is not observed. Considerations on cancer data in adulthood exposure/Indirect effect model in radiation carcinogenesis: solid cancer data supporting the indirect effect model. Possible mechanism for radiation-induced long-term increase of natural mutation frequency: genetic instability remaining in the irradiated cells which being a basis of the indirect effect model. Notes for considerations of carcinogenicity in exposed people/Difference in carcinogenic mechanisms due to age. The author concluded that the radiation-induced carcinogenesis is deeply related with the natural carcinogenesis and particularly for solid cancers, it can not be explained by the classic reductionist model. (K.H.)

  16. Lung cancer risk associated with Thr495Pro polymorphism of GHR in Chinese population.

    Science.gov (United States)

    Cao, Guochun; Lu, Hongna; Feng, Jifeng; Shu, Jian; Zheng, Datong; Hou, Yayi

    2008-04-01

    The incidence of lung cancer has been increasing over recent decades. Previous studies showed that polymorphisms of the genes involved in carcinogen-detoxication, DNA repair and cell cycle control comprise risk factors for lung cancer. Recent observations revealed that the growth hormone receptor (GHR) might play important roles in carcinogenesis and Rudd et al. found that the Thr495Pro polymorphism of GHR was strongly associated with lung cancer risk in Caucasians living in the UK (OR = 12.98, P = 0.0019, 95% CI: 1.77-infinity). To test whether this variant of GHR would modify the risk of lung cancer in Chinese population, we compared the polymorphism between 778 lung cancer patients and 781 healthy control subjects. Our results indicate that the frequency of 495Thr (2.8%) allele in cases was significantly higher than in controls (OR = 2.04, P = 0.006, 95% CI: 1.21-3.42) which indicated this allele might be a risk factor for lung cancer. Further analyses revealed Thr495Pro variant was associated with lung cancer in the subpopulation with higher risk for lung cancer: male subpopulation, still-smokers subpopulation and the subpopulation with familial history of cancer. In different histological types of lung cancer, Thr495Pro SNP was significantly associated with small cell and squamous cell lung cancer, but not with adenocarcinoma, which suggested a potential interaction between this polymorphism and metabolic pathways related to smoking. The potential gene-environment interaction on lung cancer risk was evaluated using MDR software. A significant redundant interaction between Thr495Pro polymorphism and smoking dose and familial history of cancer was identified and the combination of genetic factors and smoking status or familial history of cancer barely increased the cancer risk prediction accuracy. In conclusion, our results suggested that the Thr495Pro polymorphism of GHR was associated with the risk of lung cancer in a redundant interaction with smoking and

  17. Increased colon cancer risk after severe Salmonella infection

    Science.gov (United States)

    Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

    2018-01-01

    Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999–2015) for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1–2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite) among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD), and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09–2.10) among patients with Salmonella infection diagnosed transverse colon (SIR 2.12; 95%CI 1.38–3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73–4.76). Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade. Conclusions Patients diagnosed with severe

  18. Increased risk of antidepressant use in childhood cancer survivors

    DEFF Research Database (Denmark)

    Lund, Lasse Wegener; Winther, J.F.; Cederkvist, L

    2015-01-01

    to the National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. RESULTS: Overall, childhood cancer......AIM: Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. METHODS: Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage....... Increased HRs of 30-50% were seen for survivors of cancers of all main groups (haematological malignancies, central nervous system (CNS) and solid tumors); the highest risk was among children treated with haematopoietic stem cell transplantation (HR, 1.9; 95% CI, 1.2-3.1). Our data suggested that the risk...

  19. Promoting effects of adipose-derived stem cells on breast cancer cells are reversed by radiation therapy.

    Science.gov (United States)

    Baaße, Annemarie; Juerß, Dajana; Reape, Elaine; Manda, Katrin; Hildebrandt, Guido

    2018-04-01

    Partial breast irradiation of early breast cancer patients after lumpectomy and the use of endogenous adipose tissue (AT) for breast reconstruction are promising applications to reduce the side effects of breast cancer therapy. This study tries to investigate the possible risks associated with these therapeutic approaches. It also examines the influence of adipose derived stem cells (ADSCs) as part of the breast cancer microenvironment, and endogenous AT on breast cancer cells following radiation therapy. ADSCs, isolated from human reduction mammoplasties of healthy female donors, exhibited multilineage capacity and specific surface markers. The promoting effects of ADSCs on the growth and survival fraction of breast cancer cells were reversed by treatment with high (8 Gy) or medium (2 Gy) radiation doses. In addition, a suppressing influence on breast cancer growth could be detected by co-culturing with irradiated ADSCs (8 Gy). Furthermore the clonogenic survival of unirradiated tumor cells was reduced by medium of irradiated ADSCs. In conclusion, radiation therapy changed the interactions of ADSCs and breast cancer cells. On the basis of our work, the importance of further studies to exclude potential risks of ADSCs in regenerative applications and radiotherapy has been emphasized.

  20. Quantitative prediction of oral cancer risk in patients with oral leukoplakia.

    Science.gov (United States)

    Liu, Yao; Li, Yicheng; Fu, Yue; Liu, Tong; Liu, Xiaoyong; Zhang, Xinyan; Fu, Jie; Guan, Xiaobing; Chen, Tong; Chen, Xiaoxin; Sun, Zheng

    2017-07-11

    Exfoliative cytology has been widely used for early diagnosis of oral squamous cell carcinoma. We have developed an oral cancer risk index using DNA index value to quantitatively assess cancer risk in patients with oral leukoplakia, but with limited success. In order to improve the performance of the risk index, we collected exfoliative cytology, histopathology, and clinical follow-up data from two independent cohorts of normal, leukoplakia and cancer subjects (training set and validation set). Peaks were defined on the basis of first derivatives with positives, and modern machine learning techniques were utilized to build statistical prediction models on the reconstructed data. Random forest was found to be the best model with high sensitivity (100%) and specificity (99.2%). Using the Peaks-Random Forest model, we constructed an index (OCRI2) as a quantitative measurement of cancer risk. Among 11 leukoplakia patients with an OCRI2 over 0.5, 4 (36.4%) developed cancer during follow-up (23 ± 20 months), whereas 3 (5.3%) of 57 leukoplakia patients with an OCRI2 less than 0.5 developed cancer (32 ± 31 months). OCRI2 is better than other methods in predicting oral squamous cell carcinoma during follow-up. In conclusion, we have developed an exfoliative cytology-based method for quantitative prediction of cancer risk in patients with oral leukoplakia.

  1. Glucocorticoid receptor beta increases migration of human bladder cancer cells.

    Science.gov (United States)

    McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

    2016-05-10

    Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

  2. Understanding personal risk of oropharyngeal cancer: risk-groups for oncogenic oral HPV infection and oropharyngeal cancer.

    Science.gov (United States)

    D'Souza, G; McNeel, T S; Fakhry, C

    2017-12-01

    Incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing. There is interest in identifying healthy individuals most at risk for development of oropharyngeal cancer to inform screening strategies. All data are from 2009 to 2014, including 13 089 people ages 20-69 in the National Health and Nutrition Examination Survey (NHANES), oropharyngeal cancer cases from the Surveillance, Epidemiology, and End Results (SEER 18) registries (representing ∼28% of the US population), and oropharyngeal cancer mortality from National Center for Health Statistics (NCHS). Primary study outcomes are (i) prevalence of oncogenic HPV DNA in an oral rinse and gargle sample, and (ii) incident oropharyngeal squamous cell cancer. Oncogenic oral HPV DNA is detected in 3.5% of all adults age 20-69 years; however, the lifetime risk of oropharyngeal cancer is low (37 per 10 000). Among men 50-59 years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection, yet only 0.7% will 'ever' develop oropharyngeal cancer in their lifetime. Oncogenic oral HPV prevalence was higher in men than women, and increased with number of lifetime oral sexual partners and tobacco use. Men who currently smoked and had ≥5 lifetime oral sexual partners had 'elevated risk' (prevalence = 14.9%). Men with only one of these risk factors (i.e. either smoked and had 2-4 partners or did not smoke and had ≥5 partners) had 'medium risk' (7.3%). Regardless of what other risk factors participants had, oncogenic oral HPV prevalence was 'low' among those with only ≤1 lifetime oral sexual partner (women = 0.7% and men = 1.7%). Screening based upon oncogenic oral HPV detection would be challenging. Most groups have low oncogenic oral HPV prevalence. In addition to the large numbers of individuals who would need to be screened to identify prevalent oncogenic oral HPV, the lifetime risk of developing oropharyngeal caner among those with infection remains

  3. Lifetime growth and risk of testicular cancer.

    Science.gov (United States)

    Richiardi, Lorenzo; Vizzini, Loredana; Pastore, Guido; Segnan, Nereo; Gillio-Tos, Anna; Fiano, Valentina; Grasso, Chiara; Ciuffreda, Libero; Lista, Patrizia; Pearce, Neil; Merletti, Franco

    2014-08-01

    Adult height is associated with testicular cancer risk. We studied to what extent this association is explained by parental height, childhood height and age at puberty. We conducted a case-control study on germ-cell testicular cancer patients diagnosed in 1997-2008 and resident in the Province of Turin. Information was collected using mailed questionnaires in 2008-2011. Specifically, we asked for adult height (in cm), height at age 9 and 13 (compared to peers) and age at puberty (compared to peers). We also asked for paternal and maternal height (in cm) as indicators of genetic components of adult height. The analysis included 255 cases and 459 controls. Odds ratios (ORs) of testicular cancer were estimated for the different anthropometric variables. Adult height was associated with testicular cancer risk [OR: 1.16, 95% confidence interval (CI): 1.03-1.31 per 5-cm increase]. The risk of testicular cancer was only slightly increased for being taller vs. shorter than peers at age 9 (OR: 1.55, 95% CI: 0.91-2.64) or age 13 (OR: 1.26, 95% CI: 0.78-2.01), and parental height was not associated with testicular cancer risk. The OR for adult height was 1.32 (95% CI: 1.12-1.56) after adjustment for parental height. Among participants with small average parental height (testicular cancer for tall (>180 cm) vs. short (testicular cancer is likely to be explained by environmental factors affecting growth in early life, childhood and adolescence. © 2013 UICC.

  4. PCOS and cancer risk.

    OpenAIRE

    Tadeusz Issat; Artur J Jakimiuk

    2010-01-01

    Polycystic ovary syndrome (PCOS) affects approximately 5 to 10% of women of reproductive age. It is the most common reason of anovulation in infertile women. PCOS is accompanied by such conditions as oligo- or anovulation, hipertestosteronism, lower cell sensitivity to insulin, type II diabetes, hyperlipidemia and obesity. Each of the above-mentioned conditions is an approved risk factor proved to predispose towards cancer. However, PCOS is also a disease entity which differs in its clinical ...

  5. Hydrochlorothiazide use and risk of nonmelanoma skin cancer

    DEFF Research Database (Denmark)

    Arnspang, Sidsel; Gaist, David; Johannesdottir Schmidt, Sigrun Alba

    2018-01-01

    BACKGROUND: Hydrochlorothiazide, one of the most frequently used diuretic and antihypertensive drugs in the United States and Western Europe, is photosensitizing and has previously been linked to lip cancer. OBJECTIVE: To examine the association between hydrochlorothiazide use and the risk of basal...... cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: From the Danish Cancer Registry, we identified patients (cases) with NMSC during 2004-2012. Controls were matched 1:20 by age and sex. Cumulative hydrochlorothiazide use (1995-2012) was assessed from the Danish Prescription Registry...

  6. Colorectal Cancer Risk Assessment Tool

    Science.gov (United States)

    ... 11/12/2014 Risk Calculator About the Tool Colorectal Cancer Risk Factors Download SAS and Gauss Code Page ... Rectal Cancer: Prevention, Genetics, Causes Tests to Detect Colorectal Cancer and Polyps Cancer Risk Prediction Resources Update November ...

  7. Risks of cancer - All sites

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    This chapter describes the BEIR Committee's radiation risk models and the total risks of cancer following whole body exposure. This report focuses on the data from A-bomb survivors since this cohort contains persons of all ages at exposure. Because of large statistical uncertainties, it was not possible for the committee to provide risk estimates for cancers at all specific sites of interest. Estimates were made for risk of leukemia, breast cancer, thyroid cancer, and cancers of the respiratory and digestive systems. To obtain an estimate of the total risk of mortality from all cancers, the committee also modeled cancers other than those listed above as a group

  8. Metal arc welding and the risk of skin cancer

    DEFF Research Database (Denmark)

    Heltoft, K N; Slagor, R M; Agner, T

    2017-01-01

    OBJECTIVES: Arc welding produces the full spectrum of ultraviolet radiation and may be a contributory cause of skin cancer; however, there has been little research into this occupational hazard. The aim of this study is to explore if metal arc welding increases the risk of malignant melanoma and....../or basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) on skin areas which may possibly be exposed (neck, head, and upper extremities). METHOD: A Danish national company-based historic cohort of 4333 male metal arc welders was followed from 1987 through 2012 to identify the risk of skin cancer....... An external reference group was established including all Danish skilled and unskilled male workers with similar age distribution. Occupational histories were gathered by questionnaires in 1986 and information about skin cancer diagnoses [BCC, SCC, cutaneous malignant melanoma (CMM), and precancerous...

  9. Hydrochlorothiazide use is strongly associated with risk of lip cancer

    DEFF Research Database (Denmark)

    Pottegård, A; Hallas, J; Olesen, M

    2017-01-01

    Background: The diuretic hydrochlorothiazide is amongst the most frequently prescribed drugs in the United States and Western Europe, but there is suggestive evidence that hydrochlorothiazide use increases the risk of lip cancer. Objectives: To study the association between use of hydrochlorothia......Background: The diuretic hydrochlorothiazide is amongst the most frequently prescribed drugs in the United States and Western Europe, but there is suggestive evidence that hydrochlorothiazide use increases the risk of lip cancer. Objectives: To study the association between use...... of hydrochlorothiazide and squamous cell carcinoma of the lip. Methods: We conducted a case-control study using Danish nationwide registry data. From the Cancer Registry (2004-2012), we identified 633 case patients with squamous cell carcinoma (SCC) of the lip and matched them to 63 067 population controls using a risk......-set sampling strategy. Hydrochlorothiazide use (1995-2012) was obtained from the Prescription Registry and defined according to cumulative use. Applying conditional logistic regression, we calculated odds ratios (ORs) for SCC lip cancer associated with hydrochlorothiazide use, adjusting for predefined...

  10. Digitalis use and lung cancer risk by histological type in men.

    Science.gov (United States)

    Li, Wentao; Xie, Shao-Hua; Tse, Lap-Ah; Lagergren, Jesper

    2017-11-15

    Lung cancer risk and tumor characteristics differ between sexes. Estrogen has been suggested to counteract lung cancer development. We aimed to test the hypothesis that digitalis use decreases lung cancer risk due to its estrogenic and other anticancer properties in men. This was a nationwide Swedish population-based cohort study between July 1, 2005 and December 31, 2013. Data on the use of digitalis and organic nitrates in all male individuals were derived from the Swedish Prescribed Drug Registry. New lung cancer diagnoses among cohort participants were identified from the Swedish Cancer Registry. Cox proportional hazards regression was employed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of lung cancer in digitalis users (exposed participants) compared to users of organic nitrates without digitalis medication (unexposed participants). The study cohort contained 74,437 digitalis users and 297,301 organic nitrates users. Long-term use (≥2 years) of digitalis was associated with decreased HRs of total lung cancer (HR 0.55, 95% CI 0.39-0.79) and squamous cell carcinoma (HR 0.40, 95% CI 0.19-0.87). This large and population-based study suggests decreased risks of lung cancer overall and squamous cell carcinoma associated with long-term use of digitalis in men. © 2017 UICC.

  11. GESTATIONAL AGE AT BIRTH AND RISK OF TESTICULAR CANCER

    Science.gov (United States)

    Crump, Casey; Sundquist, Kristina; Winkleby, Marilyn A.; Sieh, Weiva; Sundquist, Jan

    2011-01-01

    Most testicular germ cell tumors originate from carcinoma in situ cells in fetal life, possibly related to sex hormone imbalances in early pregnancy. Previous studies of association between gestational age at birth and testicular cancer have yielded discrepant results and have not examined extreme preterm birth. Our objective was to determine whether low gestational age at birth is independently associated with testicular cancer in later life. We conducted a national cohort study of 354,860 men born in Sweden in 1973–1979, including 19,214 born preterm (gestational age testicular cancer incidence through 2008. A total of 767 testicular cancers (296 seminomas and 471 nonseminomatous germ cell tumors) were identified in 11.2 million person-years of follow-up. Extreme preterm birth was associated with an increased risk of testicular cancer (hazard ratio 3.95; 95% CI, 1.67–9.34) after adjusting for other perinatal factors, family history of testicular cancer, and cryptorchidism. Only five cases (three seminomas and two nonseminomas) occurred among men born extremely preterm, limiting the precision of risk estimates. No association was found between later preterm birth, post-term birth, or low or high fetal growth and testicular cancer. These findings suggest that extreme but not later preterm birth may be independently associated with testicular cancer in later life. They are based on a small number of cases and will need confirmation in other large cohorts. Elucidation of the key prenatal etiologic factors may potentially lead to preventive interventions in early life. PMID:22314417

  12. Thinking through cancer risk: characterizing smokers' process of risk determination.

    Science.gov (United States)

    Hay, Jennifer; Shuk, Elyse; Cruz, Gustavo; Ostroff, Jamie

    2005-10-01

    The perception of cancer risk motivates cancer risk reduction behaviors. However, common measurement strategies for cancer risk perceptions, which involve numerical likelihood estimates, do not adequately capture individuals' thoughts and feelings about cancer risk. To guide the development of novel measurement strategies, the authors used semistructured interviews to examine the thought processes used by smokers (N = 15) as they considered their cancer risk. They used grounded theory to guide systematic data coding and develop a heuristic model describing smokers' risk perception process that includes a cognitive, primarily rational process whereby salient personal risk factors for cancer are considered and combined, and an affective/attitudinal process, which shifts risk perceptions either up or down. The model provides a tentative explanation concerning how people hold cancer risk perceptions that diverge from rational assessment of their risks and will be useful in guiding the development of non-numerical measurements strategies for cancer risk perceptions.

  13. Association analysis identifies 65 new breast cancer risk loci.

    Science.gov (United States)

    Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley; Kar, Siddhartha; Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D; Qing Chen, Xiao; Fachal, Laura; McCue, Karen; McCart Reed, Amy E; Ghoussaini, Maya; Carroll, Jason S; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N; Arndt, Volker; Aronson, Kristan J; Arun, Banu; Auer, Paul L; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D; Castelao, Jose E; Chan, Tsun L; David Cheng, Ting-Yuan; Seng Chia, Kee; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L; Collée, Margriet; Conroy, Don M; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Devilee, Peter; Doheny, Kimberly F; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M; Ekici, Arif B; Eliassen, A Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M; García-Sáenz, José A; Gaudet, Mia M; Georgoulias, Vassilios; Giles, Graham G; Glendon, Gord; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Grenaker Alnæs, Grethe I; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N; Hartikainen, Jaana M; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I; Kim, Sung-Won; Knight, Julia A; Kosma, Veli-Matti; Kristensen, Vessela N; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Le Marchand, Loic; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Neng Lee, Chuen; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P; Ma, Edmond S K; MacInnis, Robert J; Maishman, Tom; Makalic, Enes; Malone, Kathleen E; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Taib, Nur Aishah Mohd; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F; Noh, Dong-Young; Nordestgaard, Børge G; Norman, Aaron; Olopade, Olufunmilayo I; Olson, Janet E; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V Shane; Park, Sue K; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I A; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofyeva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J T; Saloustros, Emmanouil; Sandler, Dale P; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Daniel F; Schmutzler, Rita K; Schneeweiss, Andreas; Schoemaker, Minouk J; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E; Shrubsole, Martha J; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C; Spinelli, John J; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A; Tengström, Maria; Teo, Soo H; Beth Terry, Mary; Tessier, Daniel C; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A E M; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J; Van Den Berg, David; van den Ouweland, Ans M W; van der Kolk, Lizet; van der Luijt, Rob B; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R; Wendt, Camilla; Whittemore, Alice S; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R; Har Yip, Cheng; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R; Antoniou, Antonis C; Droit, Arnaud; Andrulis, Irene L; Amos, Christopher I; Couch, Fergus J; Pharoah, Paul D P; Chang-Claude, Jenny; Hall, Per; Hunter, David J; Milne, Roger L; García-Closas, Montserrat; Schmidt, Marjanka K; Chanock, Stephen J; Dunning, Alison M; Edwards, Stacey L; Bader, Gary D; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F

    2017-11-02

    Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10 -8 . The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

  14. A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Raju, G K; Gurumurthi, K; Domike, R; Kazandjian, D; Blumenthal, G; Pazdur, R; Woodcock, J

    2016-12-01

    Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analyses. There is much interest in quantifying regulatory approaches to benefit and risk. In this work the use of a quantitative benefit-risk analysis was applied to regulatory decision-making about new drugs to treat advanced non-small cell lung cancer (NSCLC). Benefits and risks associated with 20 US Food and Drug Administration (FDA) decisions associated with a set of candidate treatments submitted between 2003 and 2015 were analyzed. For benefit analysis, the median overall survival (OS) was used where available. When not available, OS was estimated based on overall response rate (ORR) or progression-free survival (PFS). Risks were analyzed based on magnitude (or severity) of harm and likelihood of occurrence. Additionally, a sensitivity analysis was explored to demonstrate analysis of systematic uncertainty. FDA approval decision outcomes considered were found to be consistent with the benefit-risk logic. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  15. Relative risks of radiation-associated cancer: comparison of second cancer in therapeutically irradiated populations with the Japanese atomic bomb survivors

    International Nuclear Information System (INIS)

    Little, M.P.; Muirhead, C.R.; Haylock, R.G.E.; Thomas, J.M.

    1999-01-01

    In this paper the radiation-associated relative risks of second primary cancer incidence in groups treated for first primary cancer by radiotherapy are compared with radiation-associated relative risk estimates in the Japanese atomic bomb survivor cancer incidence data. For four cancer sites, namely lung cancer, bone cancer, ovarian cancer and leukaemia, the relative risks in the comparable (age at exposure, time since exposure, sex matched) subsets of the Japanese data are significantly greater than those in the majority of second cancer studies. Even when the differences between the relative risks in the Japanese atomic bomb survivors and the medical series do not approach conventional levels of statistical significance, relative risks tend to be higher in the Japanese data than in the second cancer studies. At least for leukaemia, the discrepancy between the Japanese and second cancer risks can be largely explained by cell- sterilisation effects. There are few indications of modification of radiation-associated second cancer relative risk among those treated with adjuvant chemotherapy, nor are there strong indications of modification of radiation- associated relative risk by heritable genetic factors. If anything, there is evidence that second cancer relative excess risks are lower among those patients with cancer-prone disorders than among non-susceptible patients. However, the higher underlying cancer risk in some of these medically exposed populations should also be considered, in particular for those with cancer-prone conditions, so that the absolute excess risk is sometimes higher than in the Japanese data. (orig.)

  16. Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks

    NARCIS (Netherlands)

    Rietjens, I.M.C.M.; Sotoca, A.M.; Vervoort, J.; Louisse, J.

    2013-01-01

    Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic

  17. A lung cancer risk classifier comprising genome maintenance genes measured in normal bronchial epithelial cells.

    Science.gov (United States)

    Yeo, Jiyoun; Crawford, Erin L; Zhang, Xiaolu; Khuder, Sadik; Chen, Tian; Levin, Albert; Blomquist, Thomas M; Willey, James C

    2017-05-02

    Annual low dose CT (LDCT) screening of individuals at high demographic risk reduces lung cancer mortality by more than 20%. However, subjects selected for screening based on demographic criteria typically have less than a 10% lifetime risk for lung cancer. Thus, there is need for a biomarker that better stratifies subjects for LDCT screening. Toward this goal, we previously reported a lung cancer risk test (LCRT) biomarker comprising 14 genome-maintenance (GM) pathway genes measured in normal bronchial epithelial cells (NBEC) that accurately classified cancer (CA) from non-cancer (NC) subjects. The primary goal of the studies reported here was to optimize the LCRT biomarker for high specificity and ease of clinical implementation. Targeted competitive multiplex PCR amplicon libraries were prepared for next generation sequencing (NGS) analysis of transcript abundance at 68 sites among 33 GM target genes in NBEC specimens collected from a retrospective cohort of 120 subjects, including 61 CA cases and 59 NC controls. Genes were selected for analysis based on contribution to the previously reported LCRT biomarker and/or prior evidence for association with lung cancer risk. Linear discriminant analysis was used to identify the most accurate classifier suitable to stratify subjects for screening. After cross-validation, a model comprising expression values from 12 genes (CDKN1A, E2F1, ERCC1, ERCC4, ERCC5, GPX1, GSTP1, KEAP1, RB1, TP53, TP63, and XRCC1) and demographic factors age, gender, and pack-years smoking, had Receiver Operator Characteristic area under the curve (ROC AUC) of 0.975 (95% CI: 0.96-0.99). The overall classification accuracy was 93% (95% CI 88%-98%) with sensitivity 93.1%, specificity 92.9%, positive predictive value 93.1% and negative predictive value 93%. The ROC AUC for this classifier was significantly better (p < 0.0001) than the best model comprising demographic features alone. The LCRT biomarker reported here displayed high accuracy and ease

  18. High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck

    Directory of Open Access Journals (Sweden)

    Michael J. Veness

    2007-01-01

    Full Text Available Nonmelanoma skin cancers (squamous cell and basal cell carcinomas occur at an epidemic rate in many countries with the worldwide incidence increasing. The sun-exposed head and neck are the most frequent sites for these cancers to arise and in most patients diagnosed with a cutaneous squamous cell carcinoma, local treatment is usually curative. However, a subset is diagnosed with a high-risk cutaneous squamous cell carcinoma. High-risk factors include size (> 2 cm, thickness/depth of invasion (> 4 mm, recurrent lesions, the presence of perineural invasion, location near the parotid gland, and immunosuppression. These patients have a higher risk (> 10–20% of developing metastases to regional lymph nodes (often parotid nodes, and in some cases also of experiencing local morbidity (perineural invasion, based on unfavourable primary lesion and patient factors. Despite treatment, many patients developing metastatic cutaneous squamous cell carcinoma experience mortality and morbidity usually as a consequence of uncontrolled metastatic nodal disease. It is therefore important that clinicians treating nonmelanoma skin cancers have an understanding and awareness of these high-risk patients. The aim of this article is to discuss the factors that define a high-risk patient and to present some of the issues pertinent to their management.

  19. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  20. [Nutritional risk screening and nutrition assessment for gastrointestinal cancer patients].

    Science.gov (United States)

    Du, Yan-ping; Li, Ling-ling; He, Qing; Li, Yun; Song, Hu; Lin, Yi-jia; Peng, Jun-sheng

    2012-05-01

    To investigate the nutritional status, and provide evidence for nutritional treatment option. A total of 452 patients with gastrointestinal cancer were selected, including 156 gastric cancer,117 colon cancer, and 180 rectal cancer. The nutritional risk screening 2002(NRS2002) was applied to grade the nutritional risk. A multi-frequency bioelectrical impedance analysis was used to measure the patients' body composition. Albumin (Alb), prealbumin(PA), transferring(Tf), retinol binding protein(RBP), red blood cell(RBC), hemoglobin (Hb), haematocrit(Hct) were measured after fasting. The rate of patients with NRS2002 score more than 3 was 70.5%(110/156) for gastric cancer, 53.8%(63/117) for colon cancer, and 46.7%(86/180) for rectal cancer. The score for impaired nutritional status more than 1 for gastric cancer was higher than that for colorectal cancer(Pgastric cancer(Pgastric cancer patients as compared to colorectal cancer patients(Pgastric cancer patients(Pgastric cancer and colon cancer(Pgastric cancer are prone to fat loss and therefore have a higher nutritional risk and malnutrition than those with colorectal cancer. Combination of body composition analysis and laboratory examination may achieve comprehensive evaluation of the nutritional status of patients, and provide the evidence of nutritional therapy by being combined with NRS2002 score.

  1. Second cancers after squamous cell carcinoma and adenocarcinoma of the cervix

    DEFF Research Database (Denmark)

    Chaturvedi, Anil K; Kleinerman, Ruth A; Hildesheim, Allan

    2008-01-01

    PURPOSE: Although cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) are both caused by human papillomavirus (HPV) infection, they differ in cofactors such as cigarette smoking. We assessed whether these cofactor differences translate into differences in second cancer risk. PATIENTS...... AND METHODS: We assessed second cancer risk among 85,109 cervical SCC and 10,280 AC survivors reported to population-based cancer registries in Denmark, Finland, Norway, Sweden, and the United States. Risks compared to the general population were assessed using standardized incidence ratios (SIR). RESULTS......: Overall cancer risk was significantly increased among both cervical SCC survivors (n = 10,559 second cancers; SIR, 1.31; 95% CI, 1.29 to 1.34) and AC survivors (n = 920 second cancers; SIR, 1.29; 95% CI, 1.22 to 1.38). Risks of HPV-related and radiation-related cancers were increased to a similar extent...

  2. Benefits and risks of ovarian function and reproduction for cancer development and prevention.

    Science.gov (United States)

    Schindler, Adolf E

    2011-12-01

    Ovarian function and menstrual cycle disturbances, pregnancy, and reproductive medicine procedures can either increase gynecological cancer risk or prevent cancer development. For ovarian cancer development, there are two hypotheses, which are connected with ovulation and gonadotropin secretion. Most of the ovarian cancers seem to be derived from displaced ovarian surfice epithelial cells. One year of ovulatory cycles increases the ovarian cancer risk by 6%. Ovulation between 22 and 29 years of age causes the highest risk increase per year. In contrast, progesterone or progestins appear to create protection. Lifestyle can affect or modify ovarian cancer risk. Breast cancer risk is very much related to age of menarche and menopause, pregnancy, and breast feeding. All of which are related to ovarian function and progestogenic impact that translates either into breast cancer risk increase or decrease. This is modified by body mass index, physical activity, and lifestyle in general. The risk of endometrial cancer is most closely related to endogenous progesterone during the menstrual cycle and pregnancy or by exogenous progestogens as in oral contraceptives. These effects are progestogen dose and time dependent. Endometrial cancer risk can also be increased by estrogen-producing tumors or long-term estrogen treatment.

  3. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

    Science.gov (United States)

    Song, Chang W.; Lee, Hyemi; Dings, Ruud P. M.; Williams, Brent; Powers, John; Santos, Troy Dos; Choi, Bo-Hwa; Park, Heon Joo

    2012-01-01

    The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, and significantly enhanced the radiation-induced growth delay of FSaII tumors (s.c.) in the legs of C3H mice. Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors. Conclusion: Metformin kills and radiosensitizes cancer cells and eradicates radioresistant cancer stem cells by activating AMPK and suppressing mTOR. PMID:22500211

  4. Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Neuhaus, Jacqueline; Babiker, Abdel G

    2016-01-01

    BACKGROUND:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts a...

  5. Management of Skin Cancer in the High-Risk Patient.

    Science.gov (United States)

    Behan, James W; Sutton, Adam; Wysong, Ashley

    2016-12-01

    Skin cancer is the most common of human cancers and outnumbers all other types of cancer combined in the USA by over threefold. The majority of non-melanoma skin cancers are easily treated with surgery or locally destructive techniques performed under local anesthesia in the cost-effective outpatient setting. However, there is a subset of "high-risk" cases that prove challenging in terms of morbidity, mortality, adjuvant treatment required, as well as overall cost to the health care system. In our opinion, the term "high risk" when applied to skin cancer can mean one of three things: a high-risk tumor with aggressive histologic and/or clinical features with an elevated risk for local recurrence or regional/distant metastasis, a high-risk patient with the ongoing development of multiple skin cancers, and a high-risk patient based on immunosuppression. We have recently proposed classifying NMSC as a chronic disease in a certain subset of patients. Although no consensus definition exists for a chronic disease in medicine, there are three components that are present in most definitions: duration of at least 1 year, need for ongoing medical care, and functional impairment and/or alteration of activities of daily living (ADLs) and quality of life (QOL). Immunosuppression can refer to exogenous (organ or stem cell transplant patients,) or endogenous (HIV, leukemia, lymphoma, genodermatoses with DNA mismatch repair problems or other immunosuppression) causes. These patients are at risk for high-risk tumors and/or the development of multiple tumors.

  6. Risk of second primary cancer following differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Berthe, Emmanuelle; Berthet, Pascaline; Bardet, Stephane; Henry-Amar, Michel; Michels, Jean-Jacques; Rame, Jean-Pierre; Babin, Emmanuel; Icard, Philippe; Samama, Guy; Galateau-Salle, Francoise; Mahoudeau, Jacques

    2004-01-01

    Concerns remain over the risk of cancer following differentiated thyroid carcinoma and its causes. Iodine-131 ( 131 I) and external irradiation are known to have potential carcinogenic effects. Thyroid carcinoma is a polygenic disease which may be associated with other malignancies. We investigated the incidence of second cancer and its aetiology in a cohort of 875 patients (146 men, 729 women) with differentiated thyroid carcinoma originating from Basse-Normandie, France. Cancer incidence was compared with that of the general population of the Departement du Calvados matched for age, gender and period. The cumulative proportion of second cancer was estimated using the life-table method. Factors that correlated with the risk of second cancer were studied using the Cox model. After a median follow-up of 8 years, 58 second cancers had been observed. Compared with general population incidence rates, there was an overall increased risk of second cancer in women [standardised incidence ratio (SIR)=1.52; P 0.20). Increased risk related to cancers of the genitourinary tract (SIR=3.31; P 131 I was related to the risk. These data confirm that women with differentiated thyroid carcinoma are at risk of developing a second cancer of the genitourinary tract and kidney. Only age and medical history of primary cancer before thyroid carcinoma are risk factors for second cancer. Common environmental or genetic factors as well as long-term carcinogenic effects of primary cancer therapy should be considered. (orig.)

  7. AUTOMATED ANALYSIS OF CELL DENSITY IN BREAST CANCER AS AN ADDITIONAL METHOD OF INCREASING OBJECTIVITY AND ACCURACY OF BREAST CANCER PROGNOSIS

    Directory of Open Access Journals (Sweden)

    R. M. Paltuev

    2017-01-01

    Full Text Available Introduction. In the last ten years, it became obvious that on the molecular level breast cancer is a group of heterogenous tumors. The current objective of routine clinical practice of treatment prescription includes accurate disease prognosis for every individual patient and conviction that the risk of breast cancer recurrence after adjuvant hormone therapy without adjuvant chemotherapy doesn’t increase.The study objective is to evaluate how clinical use of risk associated with cell density can in practice improve prognosis of recurrence risk in patients with breast cancer after standard clinical and pathomorphological examinations.Materials and methods. The article analyzes therapy results using data from the cumulative cancer registry of breast cancer diagnosis and treatment of the N.N. Petrov National Medical Research Oncology Center in 2000–2009. The database includes information on diagnosis, treatment, and survival of 5106 patients with breast cancer. Archived material (from 2000 to 2009 from paraffin blocks of the “targeted group” for methods of molecular and genetic profiling was poured into recipient blocks, stained with corresponding antibodies such as widely used ER, PR, HER2/neu, Ki-67 markers as well as poorly studied markers: cell density, р53, CK5/6, CK14, CD4/CD8, p63, EGFR, FOXP3, AR, FOX1.Results. The study of 1118 patients with stage T1–2N0M0 breast cancer has shown that analysis of risk associated with cell density allows to predict disease outcome. Correlation between the marker and the grade of histological malignancy is more rare than for Ki-67 determined in this patient group. As a result, determination of cell density is an additional method to increase objectivity and accuracy of breast cancer prognosis.Conclusions. Automated cell density analysis for breast cancer is almost fully operator-independent which increases accuracy and objectivity of the results. Cell density in breast cancer lower than 3000

  8. Concise review: adult multipotent stromal cells and cancer: risk or benefit?

    Science.gov (United States)

    Lazennec, Gwendal; Jorgensen, Christian

    2008-06-01

    This review focuses on the interaction between multipotent stromal cells (MSCs) and carcinoma and the possible use of MSCs in cell-based anticancer therapies. MSCs are present in multiple tissues and are defined as cells displaying the ability to differentiate in multiple lineages, including chondrocytes, osteoblasts, and adipocytes. Recent evidence also suggests that they could play a role in the progression of carcinogenesis and that MSCs could migrate toward primary tumors and metastatic sites. It is possible that MSCs could also be involved in the early stages of carcinogenesis through spontaneous transformation. In addition, it is thought that MSCs can modulate tumor growth and metastasis, although this issue remains controversial and not well understood. The immunosuppressive properties and proangiogenic properties of MSCs account, at least in part, for their effects on cancer development. On the other hand, cancer cells also have the ability to enhance MSC migration. This complex dialog between MSCs and cancer cells is certainly critical for the outcome of tumor development. Interestingly, several studies have shown that MSCs engineered to express antitumor factors could be an innovative choice as a cell-mediated gene therapy to counteract tumor growth. More evidence will be needed to understand how MSCs positively or negatively modulate carcinogenesis and to evaluate the safety of MSC use in cell-mediated gene strategies. Disclosure of potential conflicts of interest is found at the end of this article.

  9. Venous thromboembolism in ovarian cancer: incidence, risk factors and impact on survival.

    LENUS (Irish Health Repository)

    Abu Saadeh, Feras

    2013-09-01

    Ovarian cancer has a higher incidence of venous thromboembolism (VTE) than other cancers. Clear cell cancers carry the highest risk at 11-27%. The aim of this study was to identify the predisposing factors for VTE in a population of ovarian cancer patients and to determine the influence of VTE on overall survival.

  10. Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation.

    Science.gov (United States)

    Kojima, Ryosuke; Scheller, Leo; Fussenegger, Martin

    2018-01-01

    The ability to engineer custom cell-contact-sensing output devices into human nonimmune cells would be useful for extending the applicability of cell-based cancer therapies and for avoiding risks associated with engineered immune cells. Here we have developed a new class of synthetic T-cell receptor-like signal-transduction device that functions efficiently in human nonimmune cells and triggers release of output molecules specifically upon sensing contact with a target cell. This device employs an interleukin signaling cascade, whose OFF/ON switching is controlled by biophysical segregation of a transmembrane signal-inhibitory protein from the sensor cell-target cell interface. We further show that designer nonimmune cells equipped with this device driving expression of a membrane-penetrator/prodrug-activating enzyme construct could specifically kill target cells in the presence of the prodrug, indicating its potential usefulness for target-cell-specific, cell-based enzyme-prodrug cancer therapy. Our study also contributes to the advancement of synthetic biology by extending available design principles to transmit extracellular information to cells.

  11. Dual Functional Capability of Dendritic Cells - Cytokine-Induced Killer Cells in Improving Side Effects of Colorectal Cancer Therapy.

    Science.gov (United States)

    Mosińska, Paula; Gabryelska, Agata; Zasada, Malwina; Fichna, Jakub

    2017-01-01

    The aim of cancer therapy is to eradicate cancer without affecting healthy tissues. Current options available for treating colorectal cancer (CRC), including surgery, chemotherapy or radiotherapy, usually elicit multiple adverse effects and frequently fail to completely remove the tumor cells. Thus, there is a constant need for seeking cancer cell-specific therapeutics to improve the course of cancer therapy and reduce the risk of relapse. In this review we elaborate on the mechanisms underlying the immunotherapy with dendritic cells (DCs) and cytokine-induced killer (CIK) cells, and summarize their effectiveness and tolerability available clinical studies. Finally, we discuss the up-to-date combinatorial adoptive anti-cancer immunotherapy with CIK cells co-cultured with DCs that recently showed encouraging efficacy and usefulness in treating malignant disease, including CRC.

  12. Infective Endocarditis and Cancer Risk

    Science.gov (United States)

    Sun, Li-Min; Wu, Jung-Nan; Lin, Cheng-Li; Day, Jen-Der; Liang, Ji-An; Liou, Li-Ren; Kao, Chia-Hung

    2016-01-01

    Abstract This study investigated the possible relationship between endocarditis and overall and individual cancer risk among study participants in Taiwan. We used data from the National Health Insurance program of Taiwan to conduct a population-based, observational, and retrospective cohort study. The case group consisted of 14,534 patients who were diagnosed with endocarditis between January 1, 2000 and December 31, 2010. For the control group, 4 patients without endocarditis were frequency matched to each endocarditis patient according to age, sex, and index year. Competing risks regression analysis was conducted to determine the effect of endocarditis on cancer risk. A large difference was noted in Charlson comorbidity index between endocarditis and nonendocarditis patients. In patients with endocarditis, the risk for developing overall cancer was significant and 119% higher than in patients without endocarditis (adjusted subhazard ratio = 2.19, 95% confidence interval = 1.98–2.42). Regarding individual cancers, in addition to head and neck, uterus, female breast and hematological malignancies, the risks of developing colorectal cancer, and some digestive tract cancers were significantly higher. Additional analyses determined that the association of cancer with endocarditis is stronger within the 1st 5 years after endocarditis diagnosis. This population-based cohort study found that patients with endocarditis are at a higher risk for colorectal cancer and other cancers in Taiwan. The risk was even higher within the 1st 5 years after endocarditis diagnosis. It suggested that endocarditis is an early marker of colorectal cancer and other cancers. The underlying mechanisms must still be explored and may account for a shared risk factor of infection in both endocarditis and malignancy. PMID:27015220

  13. New data for venous thromboembolism in patients with small cell lung cancer: A review.

    Science.gov (United States)

    Dimakakos, Evangelos; Livanios, Konstantinos; Gkiozos, Ioannis; Charpidou, Adriani; Ntalakou, Eleutheria; Kainis, Llias; Syrigos, Konstantinos

    2017-01-01

    Malignancy is an important predisposing factor for thromboembolic disease. Patients with malignancy display 4 to 10 times greater risk than the general population. As for lung cancer, that risk seems to further increase and become up to 20 times higher. The aim of this article is to review the International literature in order to highlight for the first time, the correlation between thromboembolic disease and small cell lung cancer. PubMed, Medline and Embase databases were searched from 1990 up to 2016, for retrospective and prospective studies that investigate the correlation between thromboembolic disease and small cell lung cancer. The incidence rate of thromboembolic disease found in these studies ranged between 6.8% and 11.5%. Thromboembolic disease is associated with a reduced survival in patients with small cell lung cancer and six factors seemed to increase the risk of thromboembolism: chemotherapy, cisplatin treatment, smoking, extensive disease, the infiltration of the superior vena cava and multiple concomitant diseases. Thromboembolic disease shows an increased incidence in patients with small cell lung cancer and more research with well-designed studies is required in order to study in detail the anticoagulation treatment and the survival in small cell lung cancer patients.

  14. Cancer risk as a radiation detriment

    International Nuclear Information System (INIS)

    Servomaa, A.; Komppa, T.; Servomaa, K.

    1992-11-01

    Potential radiation detriment means a risk of cancer or other somatic disease, genetic damage of fetal injury. Quantative information about the relation between a radiation dose and cancer risk is needed to enable decision-making in radiation protection. However, assessment of cancer risk by means of the radiation dose is controversial, as epidemiological and biological information about factors affecting the origin of cancers show that risk assessment is imprecise when the radiation dose is used as the only factor. Focusing on radiation risk estimates for breast cancer, lung cancer and leukemia, the report is based on the models given in the Beir V report, on sources of radiation exposure and the uncertainty of risk estimates. Risk estimates are assessed using the relative risk model and the cancer mortality rates in Finland. Cancer incidence and mortality rates for men and women are shown in graphs as a function of age and time. Relative risks are shown as a function of time after exposure and lifetime risks as a function of age at exposure. Uncertainty factors affecting the radiation risk are examined from the point of view of epidemiology and molecular biology. (orig.)

  15. Prostate cancer: The main risk and protective factors-Epigenetic modifications.

    Science.gov (United States)

    Adjakly, Mawussi; Ngollo, Marjolaine; Dagdemir, Aslihan; Judes, Gaëlle; Pajon, Amaury; Karsli-Ceppioglu, Seher; Penault-Llorca, Frédérique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2015-02-01

    With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading cause of cancer-related death in men worldwide. Like all cancers, prostate cancer is multifactorial - there are non-modifiable risk factors like heredity, ethnicity and geographic location, but also modifiable risk factors such as diet. Diet-cancer linkages have risen to prominence in the last few years, with accruing epidemiological data pointing to between-population incidence differentials in numerous cancers. Indeed, there are correlations between fat-rich diet and risk of hormone-dependent cancers like prostate cancer and breast cancer. Diet is a risk factor for prostate cancer, but certain micronutrients in specific diets are considered protective factors against prostate cancer. Examples include tomato lycopene, green tea epigallocatechin gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer-protective effects via anti-oxidant pathways and inhibition of cell proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly genistein and daidzein, which are the best-researched to date. Soy phytoestrogens are nonsteroid molecules whose structural similarity lends them the ability to mimic the effects of 17ß-estradiol. On top of anti-oxidant effects, there is evidence that soy phytoestrogens can modulate the epigenetic modifications found in prostate cancer. We also studied the impact of phytoestrogens on epigenetic modifications in prostate cancer, with special focus on DNA methylation, miRNA-mediated regulation and histone modifications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Autoimmune gastritis mediated by CD4+ T cells promotes the development of gastric cancer.

    Science.gov (United States)

    Nguyen, Thanh-Long M; Khurana, Shradha S; Bellone, Clifford J; Capoccia, Benjamin J; Sagartz, John E; Kesman, Russell A; Mills, Jason C; DiPaolo, Richard J

    2013-04-01

    Chronic inflammation is a major risk factor for cancer, including gastric cancers and other gastrointestinal cancers. For example, chronic inflammation caused by autoimmune gastritis (AIG) is associated with an increased risk of gastric polyps, gastric carcinoid tumors, and possibly adenocarcinomas. In this study, we characterized the progression of gastric cancer in a novel mouse model of AIG. In this model, disease was caused by CD4(+) T cells expressing a transgenic T-cell receptor specific for a peptide from the H(+)/K(+) ATPase proton pump, a protein expressed by parietal cells in the stomach. AIG caused epithelial cell aberrations that mimicked most of those seen in progression of human gastric cancers, including chronic gastritis followed by oxyntic atrophy, mucous neck cell hyperplasia, spasmolytic polypeptide-expressing metaplasia, dysplasia, and ultimately gastric intraepithelial neoplasias. Our work provides the first direct evidence that AIG supports the development of gastric neoplasia and provides a useful model to study how inflammation drives gastric cancer. ©2013 AACR.

  17. The use of biologically based cancer risk models in radiation epidemiology

    International Nuclear Information System (INIS)

    Krewski, D.; Zielinski, J.M.; Hazelton, W.D.; Garner, M.J.; Moolgavkar, S.H.

    2003-01-01

    Biologically based risk projection models for radiation carcinogenesis seek to describe the fundamental biological processes involved in neoplastic transformation of somatic cells into malignant cancer cells. A validated biologically based model, whose parameters have a direct biological interpretation, can also be used to extrapolate cancer risks to different exposure conditions with some confidence. In this article, biologically based models for radiation carcinogenesis, including the two-stage clonal expansion (TSCE) model and its extensions, are reviewed. The biological and mathematical bases for such models are described, and the implications of key model parameters for cancer risk assessment examined. Specific applications of versions of the TSCE model to important epidemiologic datasets are discussed, including the Colorado uranium miners' cohort; a cohort of Chinese tin miners; the lifespan cohort of atomic bomb survivors in Hiroshima and Nagasaki; and a cohort of over 200,000 workers included in the National Dose Registry (NDR) of Canada. (author)

  18. Meat and fish consumption and the risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Rohrmann, Sabine; Linseisen, Jakob; Overvad, Kim; Wurtz, Anne Mette Lund; Roswall, Nina; Tjonneland, Anne; Boutron-Ruault, Marie-Christine; Racine, Antoine; Bastide, Nadia; Palli, Domenico; Agnoli, Claudia; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Weikert, Steffen; Steffen, Annika; Kuehn, Tilman; Li, Kuanrong; Khaw, Kay-Tee; Wareham, Nicholas J.; Bradbury, Kathryn E.; Peppa, Eleni; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Bueno-de-Mesquita, H. Bas; Peeters, Petra H. M.; Hjartaker, Anette; Skeie, Guri; Weiderpass, Elisabete; Jakszyn, Paula; Dorronsoro, Miren; Barricarte, Aurelio; Santiuste de Pablos, Carmen; Molina-Montes, Esther; Alonso de la Torre, Ramon; Ericson, Ulrika; Sonestedt, Emily; Johansson, Mattias; Ljungberg, Borje; Freisling, Heinz; Romieu, Isabelle; Cross, Amanda J.; Vergnaud, Anne-Claire; Riboli, Elio; Boeing, Heiner

    2015-01-01

    Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into

  19. Risk of cervical intra-epithelial neoplasia and invasive cancer of the cervix in DES daughters

    NARCIS (Netherlands)

    H. Verloop (Herman); F.E. van Leeuwen (F.); T.J.M. Helmerhorst (Theo); I.M.C.M. de Kok (Inge); van Erp, E.J.M.; H.H. van Boven (Hester); M.A. Rookus (Matti)

    2017-01-01

    textabstractObjective: Women exposed to diethylstilbestrol in utero (DES) have an increased risk of clear cell adenocarcinoma (CCA) of the vagina and cervix, while their risk of non-CCA invasive cervical cancer is still unclear. Methods: We studied the risk of pre-cancerous (CIN) lesions and non-CCA

  20. High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer

    DEFF Research Database (Denmark)

    Rask, Lene; Balslev, Eva; Jørgensen, Stine

    2011-01-01

    features, we performed in situ hybridization and semi-quantitative assessment of the miR-21 signal on 12 LN negative grade I (assumed low risk), and 12 LN positive grade II (high risk) breast cancers. miR-21 was predominantly seen in cancer associated fibroblast-like cells, with no difference in expression......Low-risk and high-risk breast cancer patients are stratified primarily according to their lymph node (LN) status and grading. However, some low-risk patients relapse, and some high-risk patients have a favorable clinical outcome, implying a need for better prognostic and predictive tests. Micro...... RNAs are often aberrantly expressed in cancer and microRNA-21 is upregulated in a variety of cancers, including breast cancer. High miR-21 levels have been associated with poor prognosis. To determine the cellular localization of miR-21 and to compare its expression levels with histopathological...

  1. Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

    Science.gov (United States)

    Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

    2016-01-01

    Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

  2. ABO blood type and the risk of cancer - Findings from the Shanghai Cohort Study.

    Directory of Open Access Journals (Sweden)

    Joyce Yongxu Huang

    Full Text Available ABO blood type is an inherited characteristic. The associations between ABO blood type and risk of all cancer and specific cancers were examined in a prospective cohort study of 18,244 Chinese men enrolled in 1986. During the 25 years of follow-up, 3,973 men developed cancer including 964 lung cancers, 624 colorectal cancers, 560 gastric cancers, 353 liver cancers, and 172 urinary bladder cancers. Hazard ratios (HR for all cancer and specific cancers by ABO blood type were calculated using Cox proportional hazards models. Compared with blood type A, blood type B was associated with statistically significant reduced risk of all cancers (HR, 0.91, 95% CI:0.84, 0.99. Both blood types B and AB were associated with significantly lower risk of gastrointestinal cancer and colorectal cancer, respectively. Blood type B was also associated with significantly lower risk of stomach cancer and bladder cancer, while blood type AB was associated with significantly increased risk of liver cancer. By histological type, blood types B and AB were associated with lower risk of epidermoid carcinoma and adenocarcinoma, but were not associated with risk of sarcoma, lymphoma, leukemia or other cell types of cancer. The findings of this study support a role of genetic traits related to ABO blood type in the development of cancers in the gastrointestinal and urinary tracts.

  3. ABO blood type and the risk of cancer - Findings from the Shanghai Cohort Study.

    Science.gov (United States)

    Huang, Joyce Yongxu; Wang, Renwei; Gao, Yu-Tang; Yuan, Jian-Min

    2017-01-01

    ABO blood type is an inherited characteristic. The associations between ABO blood type and risk of all cancer and specific cancers were examined in a prospective cohort study of 18,244 Chinese men enrolled in 1986. During the 25 years of follow-up, 3,973 men developed cancer including 964 lung cancers, 624 colorectal cancers, 560 gastric cancers, 353 liver cancers, and 172 urinary bladder cancers. Hazard ratios (HR) for all cancer and specific cancers by ABO blood type were calculated using Cox proportional hazards models. Compared with blood type A, blood type B was associated with statistically significant reduced risk of all cancers (HR, 0.91, 95% CI:0.84, 0.99). Both blood types B and AB were associated with significantly lower risk of gastrointestinal cancer and colorectal cancer, respectively. Blood type B was also associated with significantly lower risk of stomach cancer and bladder cancer, while blood type AB was associated with significantly increased risk of liver cancer. By histological type, blood types B and AB were associated with lower risk of epidermoid carcinoma and adenocarcinoma, but were not associated with risk of sarcoma, lymphoma, leukemia or other cell types of cancer. The findings of this study support a role of genetic traits related to ABO blood type in the development of cancers in the gastrointestinal and urinary tracts.

  4. Association between phytosterol intake and colorectal cancer risk: a case-control study.

    Science.gov (United States)

    Huang, Jing; Xu, Ming; Fang, Yu-Jing; Lu, Min-Shan; Pan, Zhi-Zhong; Huang, Wu-Qing; Chen, Yu-Ming; Zhang, Cai-Xia

    2017-03-01

    A study in rodent models showed that phytosterols protected against colon carcinogenesis, probably by inhibiting dysregulated cell cycle progression and inducing cellular apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk are quite limited. The aim of this study was to investigate dietary phytosterol intake in relation to colorectal cancer risk in the Chinese population. A case-control study was conducted from July 2010 to June 2016, recruiting 1802 eligible colorectal cancer cases plus 1813 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. A higher total intake of phytosterols was found to be associated with a 50 % reduction in colorectal cancer risk. After adjusting for various confounders, the OR of the highest quartile intake compared with the lowest quartile intake was 0·50 (95 % CI 0·41, 0·61, P trendphytosterols. An inverse association was also found between the consumption of β-sitosterol, campesterol, campestanol and colorectal cancer risk. However, stigmasterol intake was related to an increased risk of colorectal cancer. No statistically significant association was found between β-sitostanol and colorectal cancer risk. Stratified analysis by sex showed that the positive association of stigmasterol intake with colorectal cancer risk was found only in women. These data indicated that the consumption of total phytosterols, β-sitosterol, campesterol and campestanol is inversely associated with colorectal cancer risk in a Chinese population.

  5. Obesity as a Major Risk Factor for Cancer

    Directory of Open Access Journals (Sweden)

    Giovanni De Pergola

    2013-01-01

    Full Text Available The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin’s lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.

  6. Factors Influencing Cancer Risk Perception in High Risk Populations: A Systematic Review

    Science.gov (United States)

    2011-01-01

    Background Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history. Methods We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk. Results Of 1028 titles identified, 53 articles met our criteria. Most (92%) used an observational design and focused on women (70%) with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups) and few employed theory-driven analytic strategies to decipher interrelationships of factors. Conclusions Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although evolving, is still

  7. Factors Influencing Cancer Risk Perception in High Risk Populations: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Tilburt Jon C

    2011-05-01

    Full Text Available Abstract Background Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history. Methods We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk. Results Of 1028 titles identified, 53 articles met our criteria. Most (92% used an observational design and focused on women (70% with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups and few employed theory-driven analytic strategies to decipher interrelationships of factors. Conclusions Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although

  8. Infectious and dietary risk factors of oral cancer.

    Science.gov (United States)

    Meurman, Jukka H

    2010-06-01

    In addition to the classic risk factors of oral cancer, namely alcohol and tobacco, other factors both infectious and environmental are thought to be associated with the development of oral malignancy. Infections in the oral cavity may be an important preventable cause of cancer. Poor oral hygiene, periodontal disease, chronic candidiasis, human papilloma virus (HPV) and herpesvirus infections link statistically with cancer but the mechanisms involved are largely unknown. Infections may trigger cell proliferation, inhibit apoptosis, interfere with cellular signaling mechanisms and up-regulate tumor promoters. In addition, several oral micro-organisms metabolize alcohol to carcinogenic acetaldehyde thus explaining the association between poor oral hygiene, alcohol consumption and carcinogenesis. With regards to dietary factors the Mediterranean-type fruit and vegetable rich diet has been shown to reduce the risk of oral cancer but the evidence is weak, the effect of individual food components and trace elements on carcinogenesis remains unclear at present. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

  10. Saw palmetto supplement use and prostate cancer risk.

    Science.gov (United States)

    Bonnar-Pizzorno, Raven M; Littman, Alyson J; Kestin, Mark; White, Emily

    2006-01-01

    Saw palmetto is an herb used to treat the symptoms of benign prostatic hyperplasia. In vitro studies have found that saw palmetto inhibits growth of prostatic cancer cells and may induce apoptosis. To evaluate whether saw palmetto supplements are associated with a reduced risk of prostate cancer, we conducted a prospective cohort study of 35,171 men aged 50-76 yr in western Washington state. Subjects completed questionnaires between 2000 and 2002 on frequency of use of saw palmetto supplements and saw palmetto-containing multivitamins over the previous 10 yr in addition to other information on supplement intake, medical history, and demographics. Men were followed through December 2003 (mean of 2.3 yr of follow-up) via the western Washington Surveillance, Epidemiology, and End Results cancer registry, during which time 580 developed prostate cancer. Ten percent of the cohort used saw palmetto at least once per week for a year in the 10 yr before baseline. No association was found between this level of use of saw palmetto and risk of prostate cancer development [hazard ratio (HR) = 0.95; 95% confidence interval = 0.74-1.23] or with increasing frequency or duration of use. In this free-living population, use of commercial saw palmetto, which varies widely in dose and constituent ratios, was not associated with prostate cancer risk.

  11. Long working hours and cancer risk

    DEFF Research Database (Denmark)

    Heikkila, Katriina; Nyberg, Solja T.; Madsen, Ida E. H.

    2016-01-01

    in 116 462 men and women who were free of cancer at baseline. Incident cancers were ascertained from national cancer, hospitalisation and death registers; weekly working hours were self-reported. Results: During median follow-up of 10.8 years, 4371 participants developed cancer (n colorectal cancer: 393......Background: Working longer than the maximum recommended hours is associated with an increased risk of cardiovascular disease, but the relationship of excess working hours with incident cancer is unclear. Methods: This multi-cohort study examined the association between working hours and cancer risk......; n lung cancer: 247; n breast cancer: 833; and n prostate cancer: 534). We found no clear evidence for an association between working hours and the overall cancer risk. Working hours were also unrelated the risk of incident colorectal, lung or prostate cancers. Working greater than or equal to55 h...

  12. Contralateral breast cancer risk

    International Nuclear Information System (INIS)

    Unnithan, Jaya; Macklis, Roger M.

    2001-01-01

    The use of breast-conserving treatment approaches for breast cancer has now become a standard option for early stage disease. Numerous randomized studies have shown medical equivalence when mastectomy is compared to lumpectomy followed by radiotherapy for the local management of this common problem. With an increased emphasis on patient involvement in the therapeutic decision making process, it is important to identify and quantify any unforeseen risks of the conservation approach. One concern that has been raised is the question of radiation- related contralateral breast cancer after breast radiotherapy. Although most studies do not show statistically significant evidence that patients treated with breast radiotherapy are at increased risk of developing contralateral breast cancer when compared to control groups treated with mastectomy alone, there are clear data showing the amount of scattered radiation absorbed by the contralateral breast during a routine course of breast radiotherapy is considerable (several Gy) and is therefore within the range where one might be concerned about radiogenic contralateral tumors. While radiation related risks of contralateral breast cancer appear to be small enough to be statistically insignificant for the majority of patients, there may exist a smaller subset which, for genetic or environmental reasons, is at special risk for scatter related second tumors. If such a group could be predicted, it would seem appropriate to offer either special counselling or special prevention procedures aimed at mitigating this second tumor risk. The use of genetic testing, detailed analysis of breast cancer family history, and the identification of patients who acquired their first breast cancer at a very early age may all be candidate screening procedures useful in identifying such at- risk groups. Since some risk mitigation strategies are convenient and easy to utilize, it makes sense to follow the classic 'ALARA' (as low as reasonably

  13. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  14. Oesophageal squamous cell cancer in a South African tertiary hospital

    African Journals Online (AJOL)

    The site of tumour location was in the middle 96 (60.4%), distal 42(26.4%) and proximal 17(10.6%) oesophagus. The male to female ratio was 1:1 ... with HIV negative patients. Key words: Oesophageal cancer, squamous cell cancer, HIV, dental hygiene, socioeconomic status, South Africa, esophageal cancer, risk factors ...

  15. Inflammatory Genetic Markers of Prostate Cancer Risk

    International Nuclear Information System (INIS)

    Tindall, Elizabeth A.; Hayes, Vanessa M.; Petersen, Desiree C.

    2010-01-01

    Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk

  16. Inflammatory Genetic Markers of Prostate Cancer Risk

    Energy Technology Data Exchange (ETDEWEB)

    Tindall, Elizabeth A.; Hayes, Vanessa M. [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia); University of New South Wales, Kensington Campus, Sydney, NSW 2052 (Australia); Petersen, Desiree C., E-mail: dpetersen@ccia.unsw.edu.au [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia)

    2010-06-08

    Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk.

  17. Work stress and risk of cancer

    DEFF Research Database (Denmark)

    Heikkilä, Katriina; Nyberg, Solja T; Theorell, Töres

    2013-01-01

    To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers.......To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers....

  18. The lung cancer risk from inhalation of radon-222 decay products

    International Nuclear Information System (INIS)

    Jacobi, W.

    1975-05-01

    The results of surveys in the USA and the CSSR on the lung cancer mortality among uranium miners are compared. The relation between the observed excess lung cancer mortality and the cumulative exposure of these miners by inhaled Rn-daughters is discussed and the risk coefficients for radiation-induced lung cancer are estimated. The relative risk coefficients of both study groups of U-miners agree within the confidence limits and are in the range of 0.001 to 0.005 WLM -1 . The derived absolute risk coefficients of 20 +- 10 (USA group) and 150 +- 50 (CSSR group) additional lung cancer deaths per WLM and 10 6 miners are, however, significantly different. The influence of synergistic or cocancerogenic actions is discussed. The increase of lung cancer mortality with Rn-exposure is significantly correlated with an increase of the small-cell, undifferentiated type of carcinoma. (author)

  19. Isolation and Characterization of Cancer Stem Cells of the Non-Small-Cell Lung Cancer (A549) Cell Line.

    Science.gov (United States)

    Halim, Noor Hanis Abu; Zakaria, Norashikin; Satar, Nazilah Abdul; Yahaya, Badrul Hisham

    2016-01-01

    Cancer is a major health problem worldwide. The failure of current treatments to completely eradicate cancer cells often leads to cancer recurrence and dissemination. Studies have suggested that tumor growth and spread are driven by a minority of cancer cells that exhibit characteristics similar to those of normal stem cells, thus these cells are called cancer stem cells (CSCs). CSCs are believed to play an important role in initiating and promoting cancer. CSCs are resistant to currently available cancer therapies, and understanding the mechanisms that control the growth of CSCs might have great implications for cancer therapy. Cancer cells are consist of heterogeneous population of cells, thus methods of identification, isolation, and characterisation of CSCs are fundamental to obtain a pure CSC populations. Therefore, this chapter describes in detail a method for isolating and characterizing a pure population of CSCs from heterogeneous population of cancer cells and CSCs based on specific cell surface markers.

  20. Perceptions of Risk of Developing Skin Cancer for Diverse Audiences: Enhancing Relevance of Sun Protection to Reduce the Risk.

    Science.gov (United States)

    Robinson, June K; Friedewald, John; Gordon, Elisa J

    2016-03-01

    Sixty-five percent of kidney transplant recipients (KTRs) develop squamous cell carcinoma (SCC). Perceptions of risk of developing skin cancer, amelioration of this risk with sun protection, and having choices among sun protection strategies may enhance sun protection use by KTRS, who are at greater risk than the general population. Thirty KTRs stratified among non-Hispanic Whites, non-Hispanic Blacks, and Hispanic/Latinos evaluated three versions of the interactive, web-based, electronic sun protection program and suggested refinements. The sequence of content presentation prepared the participant to accept the credibility, accuracy, and relevance of the message. Beginning with informing participants that using sun protection reduces the chance of developing skin cancer made the information credible to KTRs. Showing skin cancer on all skin types and patient testimonials enhanced participants' awareness of their susceptibility to develop skin cancer and primed patients to receive their personal risk of developing skin cancer. Coupling presentation of knowledge about the benefits of sun protection in reducing the risk of developing skin cancer with the personal risk of getting the disease was essential to KTRs believing that they could influence their health outcome.

  1. The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Aksglaede, Lise; Juul, Anders

    2011-01-01

    This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy.......This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy....

  2. From embryonic stem cells to testicular germ cell cancer-- should we be concerned?

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Sonne, Si Brask; Hoei-Hansen, Christina E

    2006-01-01

    that initial hypothesis but also indicating that CIS cells have a striking phenotypic similarity to embryonic stem cells (ESC). Many cancers have been proposed to originate from tissue-specific stem cells [so-called 'cancer stem cells' (CSC)] and we argue that CIS may be a very good example of a CSC......, but with exceptional features due to the retention of embryonic pluripotency. In addition, considering the fact that pre-invasive CIS cells are transformed from early fetal cells, possibly due to environmentally induced alterations of the niche, we discuss potential risks linked to the uncontrolled therapeutic use......Since the discovery of testicular carcinoma in situ (CIS) -- the precursor cell for the vast majority of germ cell tumours -- it has been proposed that CIS cells could be derived from transformed primordial germ cells or gonocytes. Here, we review recent discoveries not only substantiating...

  3. Cancer risks: Strategies for elimination

    International Nuclear Information System (INIS)

    Bannasch, P.

    1987-01-01

    This book deals with the possibilities for identifying and eliminating cancer risk factors. The current state of knowledge on the detection, assessment and elimination of chemical, physical (radiation), and biological (viruses) risk factors are comprehensively presented in 15 contributions. Chemical risk factors resulting from smoking and environmental contamination are given special attention. The coverage of cancer risks by radiation includes some of the consequences of the Chernobyl disaster. Finally, the discussion of the possible risks that certain viruses hold for cancer in man is intended to further the development of vaccinations against these viral infections. The information is directed not only at specialists, but also at a wider interested audience. Its primary aim is to convey established findings that are already being used for cancer prevention. Furthermore, the book aims to promote more intense research in the field of primary cancer prevention. Contents: General aspects; chemical carcinogens: Risk assessment; chemical carcinogens: Primary prevention; physical carcinogens - Oncogenic viruses and subject index

  4. Green tea’s effects in the breast cancer risk

    Directory of Open Access Journals (Sweden)

    Carlos Pardos-Sevilla

    2014-04-01

    Full Text Available Phytochemicals like catechins from green tea might modify the epigenome and transcirptome of tumoral cells. The objective of the present review is to retrospectively evaluate literature examining the mechanisms throughout the green tea could exert a protective effect on breast cancer risk. In this work, more than 100 articles published during the last 15 years that relate tea consumption and breast cancer prevalence and development have been analysed. Green tea polyphenols can reduce risk of breast cancer throughout the inhibition of estrogenic and chemotoxic activity in liver, stimulation of metabolic pathway of glutathione conjugation, improvement of the metabolic syndrome, as well as control of immune system regulation, oxidative stress and DNA methylation. Although in vitro and animal studies show the potential ability of green tea polyphenols to act against breast cancer, the lack of experiments in humans, are the major factors in limiting us to conduct dietary recommendations based on scientific evidence for the management of patients with breast cancer.

  5. Breast Cancer Risk in American Women

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Risk in American Women On This Page What ... risk of developing the disease. Personal history of breast cancer : Women who have had breast cancer are more ...

  6. Postnatal risk factors for testicular cancer: The EPSAM case-control study.

    Science.gov (United States)

    Moirano, Giovenale; Zugna, Daniela; Grasso, Chiara; Mirabelli, Dario; Lista, Patrizia; Ciuffreda, Libero; Segnan, Nereo; Merletti, Franco; Richiardi, Lorenzo

    2017-11-01

    Testicular cancer is considered to originate from an impaired differentiation of fetal germ cells, but puberty could represent another time window of susceptibility. Our study aimed at investigating the association between environmental exposures acting during puberty/adolescence (13-19 years of age) and the risk of testicular cancer. We used data of the EPSAM study, a case-control study on germ-cell testicular cancer conducted in the province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Histologically confirmed cases (n = 255) and controls (n = 459) completed a postal questionnaire focusing in particular on the pubertal period (namely age 13 years) with questions on physical activity (competitive sports, gardening), lifestyle (alcohol consumption, smoking), occupational history and medical conditions. All analyses were adjusted for the matching variables, cryptorchidism and educational level. Having done at least one competitive sport during puberty (odds ratio [OR]: 0.72, 95% confidence interval: 0.52-1.00), gardening activities during puberty (OR: 0.62, 0.42-0.94) and having a lower weight than peers during puberty (OR: 0.64, 0.42-0.97) were all inversely associated with the risk of testicular cancer. No evidence of association between smoking or alcohol consumption during puberty and the risk of testicular cancer was observed. Regarding agriculture-related occupations, we found an association with the risk of testicular cancer both for occasional jobs during puberty (OR: 2.40, 95% CI: 1.08-5.29) and ever employment in adolescence (OR: 2.59, 95% CI: 0.83-8.10). Our results suggest that postnatal exposures could play a role in testicular cancer aetiology, at least when acting in puberty or adolescence. © 2017 UICC.

  7. A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer.

    Science.gov (United States)

    Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min

    2012-12-01

    According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research.

  8. Diabetes, insulin and cancer risk

    OpenAIRE

    Yang, Xi-Lin; Chan, Juliana CN

    2012-01-01

    There is a consensus that both type 1 and type 2 diabetes are associated with a spectrum of cancers but the underlying mechanisms are largely unknown. On the other hand, there are ongoing debates about the risk association of insulin use with cancer. We have briefly reviewed recent related research on exploration of risk factors for cancer and pharmacoepidemiological investigations into drug use in diabetes on the risk of cancer, as well as the current understanding of metabolic pathways impl...

  9. Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis

    DEFF Research Database (Denmark)

    Cunningham, J M; Vierkant, R A; Sellers, T A

    2009-01-01

    BACKGROUND: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide. METHODS: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin......-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) were genotyped using an Illumina assay. RESULTS: Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk...... of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population [odds ratio, OR(BB vs AA) 2.81 (1.29-6.09), P=0.01] was also observed...

  10. Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Narumol Bhummaphan

    2015-01-01

    Full Text Available As cancer stem cells (CSCs contribute to malignancy, metastasis, and relapse of cancers, potential of compound in inhibition of CSCs has garnered most attention in the cancer research as well as drug development fields recently. Herein, we have demonstrated for the first time that gigantol, a pure compound isolated from Dendrobium draconis, dramatically suppressed stem-like phenotypes of human lung cancer cells. Gigantol at nontoxic concentrations significantly reduced anchorage-independent growth and survival of the cancer cells. Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs. Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1. Moreover, we revealed that gigantol decreased stemness in the cancer cells by suppressing the activation of protein kinase B (Akt signal which in turn decreased the cellular levels of pluripotency and self-renewal factors Oct4 and Nanog. In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs.

  11. Long-term nitrite inhalant exposure and cancer risk in MSM

    Science.gov (United States)

    Dutta, Anupriya; Uno, Hajime; Holman, Alex; Lorenz, David R.; Wolinsky, Steven M.; Gabuzda, Dana

    2017-01-01

    Objectives: Nitrite inhalants (poppers) are commonly used recreational drugs among MSM and were previously associated with elevated rates of high-risk sexual behavior, HIV and human herpesvirus type 8 (HHV-8) seroconversion, and transient immunosuppressive effects in experimental models. Whether long-term popper use is associated with cancer risk among MSM in the HAART era is unclear. Design: Prospective cohort study of cancer risk in 3223 HIV-infected and uninfected MSM in the Multicenter AIDS Cohort Study from 1996–2010. Methods: Poisson regression models were used to examine the association between heavy popper use (defined as daily or weekly use for at least 1 year) and risk of individual cancers or composite category of virus-associated cancers. Results: Among all participants, heavy popper use was not associated with increased risk of any individual cancers. Among HIV-uninfected men aged 50–70, heavy popper use was associated with increased risk of virus-associated cancer with causes linked to human papillomavirus, HHV-8, and Epstein–Barr virus in models adjusted for demographics, number of sexual partners, immunological parameters (CD4+ cell counts or CD4+/CD8+ ratios), and hepatitis B and C viruses [incidence rate ratio (IRR), 95% confidence interval (CI) 3.24, 1.05–9.96], or sexually transmitted infections (IRR 3.03, 95% CI, 1.01–9.09), as was cumulative use over a 5-year period (IRR 1.012, 95% CI 1.003–1.021; P = 0.007). There was no significant association between heavy popper use and virus-associated cancer in HIV-infected men. Conclusions: Long-term heavy popper use is associated with elevated risk of some virus-associated cancers with causes related to human papillomavirus, HHV-8, and Epstein–Barr virus infections in older HIV-uninfected MSM independent of sexual behavior and immunological parameters. PMID:28441176

  12. Common breast cancer risk alleles and risk assessment

    DEFF Research Database (Denmark)

    Näslund-Koch, C; Nordestgaard, B G; Bojesen, S E

    2017-01-01

    general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0-2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score......, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer. RESULTS: Breast cancer incidence in the 19,010 women was increased across allele sum quintiles (log-rank trend test; p=1*10(-12)), but not incidence of other cancers (p=0.41). Age- and study-adjusted hazard...... ratio for the 5(th) vs. 1(st) allele sum quintile was 1.82(95% confidence interval;1.53-2.18). Corresponding hazard ratios per allele were 1.04(1.03-1.05) and 1.05(1.02-1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year old women, the starting age for screening...

  13. Current Status on Stem Cells and Cancers of the Gastric Epithelium

    Directory of Open Access Journals (Sweden)

    Werner Hoffmann

    2015-08-01

    Full Text Available Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells.

  14. Risk factors for skin cancer among Finnish airline cabin crew.

    Science.gov (United States)

    Kojo, Katja; Helminen, Mika; Pukkala, Eero; Auvinen, Anssi

    2013-07-01

    Increased incidence of skin cancers among airline cabin crew has been reported in several studies. We evaluated whether the difference in risk factor prevalence between Finnish airline cabin crew and the general population could explain the increased incidence of skin cancers among cabin crew, and the possible contribution of estimated occupational cosmic radiation exposure. A self-administered questionnaire survey on occupational, host, and ultraviolet radiation exposure factors was conducted among female cabin crew members and females presenting the general population. The impact of occupational cosmic radiation dose was estimated in a separate nested case-control analysis among the participating cabin crew (with 9 melanoma and 35 basal cell carcinoma cases). No considerable difference in the prevalence of risk factors of skin cancer was found between the cabin crew (N = 702) and the general population subjects (N = 1007) participating the study. The mean risk score based on all the conventional skin cancer risk factors was 1.43 for cabin crew and 1.44 for general population (P = 0.24). Among the cabin crew, the estimated cumulative cosmic radiation dose was not related to the increased skin cancer risk [adjusted odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.57-1.00]. The highest plausible risk of skin cancer for estimated cosmic radiation dose was estimated as 9% per 10 mSv. The skin cancer cases had higher host characteristics scores than the non-cases among cabin crew (adjusted OR = 1.43, 95% CI: 1.01-2.04). Our results indicate no difference between the female cabin crew and the general female population in the prevalence of factors generally associated with incidence of skin cancer. Exposure to cosmic radiation did not explain the excess of skin cancer among the studied cabin crew in this study.

  15. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-01-01

    Highlights: ► Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. ► Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. ► Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. ► Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. ► This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called “cancer stem cells”, within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the “stemness” of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  16. Are cancer cells really softer than normal cells?

    Science.gov (United States)

    Alibert, Charlotte; Goud, Bruno; Manneville, Jean-Baptiste

    2017-05-01

    Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  17. Cancer risk from inorganics

    International Nuclear Information System (INIS)

    Swierenga, S.H.; Gilman, J.P.; McLean, J.R.

    1987-01-01

    Inorganic metals and minerals for which there is evidence of carcinogenicity are identified. The risk of cancer from contact with them in the work place, the general environment, and under conditions of clinical (medical) exposure is discussed. The evidence indicates that minerals and metals most often influence cancer development through their action as cocarcinogens. The relationship between the physical form of mineral fibers, smoking and carcinogenic risk is emphasized. Metals are categorized as established (As, Be, Cr, Ni), suspected (Cd, Pb) and possible carcinogens, based on the existing in vitro, animal experimental and human epidemiological data. Cancer risk and possible modes of action of elements in each class are discussed. Views on mechanisms that may be responsible for the carcinogenicity of metals are updated and analysed. Some specific examples of cancer risks associated with the clinical use of potentially carcinogenic metals and from radioactive pharmaceuticals used in therapy and diagnosis are presented. Questions are raised as to the effectiveness of conventional dosimetry in accurately measuring risk from radiopharmaceuticals. 302 references

  18. Population-Attributable Risk Proportion of Clinical Risk Factors for Breast Cancer.

    Science.gov (United States)

    Engmann, Natalie J; Golmakani, Marzieh K; Miglioretti, Diana L; Sprague, Brian L; Kerlikowske, Karla

    2017-09-01

    Many established breast cancer risk factors are used in clinical risk prediction models, although the proportion of breast cancers explained by these factors is unknown. To determine the population-attributable risk proportion (PARP) for breast cancer associated with clinical breast cancer risk factors among premenopausal and postmenopausal women. Case-control study with 1:10 matching on age, year of risk factor assessment, and Breast Cancer Surveillance Consortium (BCSC) registry. Risk factor data were collected prospectively from January 1, 1996, through October 31, 2012, from BCSC community-based breast imaging facilities. A total of 18 437 women with invasive breast cancer or ductal carcinoma in situ were enrolled as cases and matched to 184 309 women without breast cancer, with a total of 58 146 premenopausal and 144 600 postmenopausal women enrolled in the study. Breast Imaging Reporting and Data System (BI-RADS) breast density (heterogeneously or extremely dense vs scattered fibroglandular densities), first-degree family history of breast cancer, body mass index (>25 vs 18.5-25), history of benign breast biopsy, and nulliparity or age at first birth (≥30 years vs breast cancer. Of the 18 437 women with breast cancer, the mean (SD) age was 46.3 (3.7) years among premenopausal women and 61.7 (7.2) years among the postmenopausal women. Overall, 4747 (89.8%) premenopausal and 12 502 (95.1%) postmenopausal women with breast cancer had at least 1 breast cancer risk factor. The combined PARP of all risk factors was 52.7% (95% CI, 49.1%-56.3%) among premenopausal women and 54.7% (95% CI, 46.5%-54.7%) among postmenopausal women. Breast density was the most prevalent risk factor for both premenopausal and postmenopausal women and had the largest effect on the PARP; 39.3% (95% CI, 36.6%-42.0%) of premenopausal and 26.2% (95% CI, 24.4%-28.0%) of postmenopausal breast cancers could potentially be averted if all women with heterogeneously or extremely dense

  19. Skin Cancer: Biology, Risk Factors & Treatment

    Science.gov (United States)

    ... turn Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer 2013 Table ... Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma ...

  20. Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli-sani cohort and cellular models.

    Science.gov (United States)

    Pounis, George; Tabolacci, Claudio; Costanzo, Simona; Cordella, Martina; Bonaccio, Marialaura; Rago, Livia; D'Arcangelo, Daniela; Filippo Di Castelnuovo, Augusto; de Gaetano, Giovanni; Donati, Maria Benedetta; Iacoviello, Licia; Facchiano, Francesco

    2017-07-01

    Meta-analytic data on the effect of coffee in prostate cancer risk are controversial. Caffeine as a bioactive compound of coffee has not yet been studied in deep in vitro. Our study aimed at evaluating in a population cohort the effect of Italian-style coffee consumption on prostate cancer risk and at investigating in vitro the potential antiproliferative and antimetastatic activity of caffeine on prostate cancer cell lines. 6,989 men of the Moli-sani cohort aged ≥50 years were followed for a mean of 4.24 ± 1.35 years and 100 new prostate cancer cases were identified. The European Prospective Investigation into Cancer and Nutrition-Food Frequency Questionnaire was used for the dietary assessment and the evaluation of Italian-style coffee consumption. Two human prostate cancer cell lines, PC-3 and DU145, were tested with increasing concentrations of caffeine, and their proliferative/metastatic features were evaluated. The newly diagnosed prostate cancer participants presented lower coffee consumption (60.1 ± 51.3 g/day) compared to the disease-free population (74.0 ± 51.7 g/day) (p 3 cups/day) had 53% lower prostate cancer risk as compared to participants at the lowest consumption (0-2 cups/day) (p = 0.02). Both human prostate cancer cell lines treated with caffeine showed a significant reduction in their proliferative and metastatic behaviors (p coffee consumption of prostate cancer risk (>3 cups/day) was observed in epidemiological level. Caffeine appeared to exert both antiproliferative and antimetastatic activity on two prostate cancer cell lines, thus providing a cellular confirmation for the cohort study results. © 2017 UICC.

  1. Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.

    Science.gov (United States)

    Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi

    2013-12-31

    While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001.

  2. ABO blood type and the risk of cancer – Findings from the Shanghai Cohort Study

    Science.gov (United States)

    Wang, Renwei; Gao, Yu-Tang

    2017-01-01

    ABO blood type is an inherited characteristic. The associations between ABO blood type and risk of all cancer and specific cancers were examined in a prospective cohort study of 18,244 Chinese men enrolled in 1986. During the 25 years of follow-up, 3,973 men developed cancer including 964 lung cancers, 624 colorectal cancers, 560 gastric cancers, 353 liver cancers, and 172 urinary bladder cancers. Hazard ratios (HR) for all cancer and specific cancers by ABO blood type were calculated using Cox proportional hazards models. Compared with blood type A, blood type B was associated with statistically significant reduced risk of all cancers (HR, 0.91, 95% CI:0.84, 0.99). Both blood types B and AB were associated with significantly lower risk of gastrointestinal cancer and colorectal cancer, respectively. Blood type B was also associated with significantly lower risk of stomach cancer and bladder cancer, while blood type AB was associated with significantly increased risk of liver cancer. By histological type, blood types B and AB were associated with lower risk of epidermoid carcinoma and adenocarcinoma, but were not associated with risk of sarcoma, lymphoma, leukemia or other cell types of cancer. The findings of this study support a role of genetic traits related to ABO blood type in the development of cancers in the gastrointestinal and urinary tracts. PMID:28880901

  3. Lung cancer risk at low doses of alpha particles

    International Nuclear Information System (INIS)

    Hofmann, W.; Katz, R.; Zhang, C.X.

    1986-01-01

    A survey of inhabitant exposures arising from the inhalation of 222 Rn and 220 Rn progeny, and lung cancer mortality has been carried out in two adjacent areas in Guangdong Province, People's Republic of China, designated as the high background and the control area. Annual exposure rates are 0.38 working level months (WLM) per year in the high background, and 0.16 WLM/yr in the control area. In 14 yr of continuous study, from 1970 to 1983, age-adjusted mortality rates were found to be 2.7 per 10(5) living persons of all ages in the high background area, and 2.9 per 10(5) living persons in the control area. From this data, we conclude that we are unable to determine excess lung cancers over the normal fluctuations below a cumulative exposure of 15 WLM. This conclusion is supported by lung cancer mortality data from Austrian and Finnish high-background areas. A theoretical analysis of epidemiological data on human lung cancer incidence from inhaled 2 ]2'' 2 Rn and 220 Rn progeny, which takes into account cell killing as competitive with malignant transformation, leads to the evaluation of a risk factor which is either a linear-exponential or a quadratic-exponential function of the alpha-particle dose. Animal lung cancer data and theoretical considerations can be supplied to support either hypothesis. Thus we conclude that at our current stage of knowledge both the linear-exponential and the quadratic-exponential extrapolation to low doses seem to be equally acceptable for Rn-induced lung cancer risk, possibly suggesting a linear-quadratic transformation function with an exponential cell-killing term, or the influence of risk-modifying factors such as repair or proliferation stimuli

  4. Enantioselective Effects of o,p'-DDT on Cell Invasion and Adhesion of Breast Cancer Cells: Chirality in Cancer Development.

    Science.gov (United States)

    He, Xiangming; Dong, Xiaowu; Zou, Dehong; Yu, Yang; Fang, Qunying; Zhang, Quan; Zhao, Meirong

    2015-08-18

    The o,p'-dichlorodiphenyltrichloroethane (DDT) with a chiral center possesses enantioselective estrogenic activity, in which R-(-)-o,p'-DDT exerts a more potent estrogenic effect than S-(+)-o,p'-DDT. Although concern regarding DDT exposure and breast cancer has increased in recent decades, the mode of enantioselective action of o,p'-DDT in breast cancer development is still unknown. Herein, we conducted a systematic study of the effect of o,p'-DDT on stereoselective breast tumor cell progression in a widely used in vitro breast tumor cell model, MCF-7 cells. We demonstrated that R-(-)-o,p'-DDT promoted more cancer cell invasion mediated by the human estrogen receptor (ER) by inducing invasion-promoted genes (matrix metalloproteinase-2 and -9 and human telomerase reverse transcriptase) and inhibiting invasion-inhibited genes (tissue inhibitor of metalloproteinase-1 and -4). Molecular docking verified that the binding affinity between R-(-)-o,p'-DDT and human ER was stronger than that of S-(+)-o,p'-DDT. The enantioselective-induced decrease in cell-to-cell adhesion may involve the downregulation of adhesion-promoted genes (E-cadherin and β-catenin). For the first time, these results reveal that estrogenic-like chiral compounds are of significant concern in the progression of human cancers and that human health risk assessment of chiral chemicals should consider enantioselectivity.

  5. How Can We Treat Cancer Disease Not Cancer Cells?

    Science.gov (United States)

    Kim, Kyu-Won; Lee, Su-Jae; Kim, Woo-Young; Seo, Ji Hae; Lee, Ho-Young

    2017-01-01

    Since molecular biology studies began, researches in biological science have centered on proteins and genes at molecular level of a single cell. Cancer research has also focused on various functions of proteins and genes that distinguish cancer cells from normal cells. Accordingly, most contemporary anticancer drugs have been developed to target abnormal characteristics of cancer cells. Despite the great advances in the development of anticancer drugs, vast majority of patients with advanced cancer have shown grim prognosis and high rate of relapse. To resolve this problem, we must reevaluate our focuses in current cancer research. Cancer should be considered as a systemic disease because cancer cells undergo a complex interaction with various surrounding cells in cancer tissue and spread to whole body through metastasis under the control of the systemic modulation. Human body relies on the cooperative interaction between various tissues and organs, and each organ performs its specialized function through tissue-specific cell networks. Therefore, investigation of the tumor-specific cell networks can provide novel strategy to overcome the limitation of current cancer research. This review presents the limitations of the current cancer research, emphasizing the necessity of studying tissue-specific cell network which could be a new perspective on treating cancer disease, not cancer cells.

  6. Coffee Consumption and Lung Cancer Risk: The Japan Public Health Center-Based Prospective Study.

    Science.gov (United States)

    Narita, Saki; Saito, Eiko; Sawada, Norie; Shimazu, Taichi; Yamaji, Taiki; Iwasaki, Motoki; Sasazuki, Shizuka; Noda, Mitsuhiko; Inoue, Manami; Tsugane, Shoichiro

    2018-04-05

    Many epidemiological studies have indicated a positive association between coffee intake and lung cancer risk, but such findings were suggested to be confounded by smoking. Furthermore, only a few of these studies have been conducted in Asia. Here, we investigated the association between coffee intake and lung cancer risk in one of the largest prospective cohort studies in Japan. We investigated the association of coffee drinking and subsequent incidence of lung cancer among 41,727 men and 45,352 women in the Japan Public Health Center-based Prospective Study using Cox proportional hazards regression, with adjustment for potential confounders and by strata of smoking status. Coffee and other dietary intakes were assessed once at baseline with a food frequency questionnaire (FFQ). During 1,481,887 person-years of follow-up between 1990 and 2011, a total of 1,668 lung cancer cases were identified. In a multivariate regression model, coffee consumption was not associated with risk of lung cancer (HR 1.16; 95% CI, 0.82-1.63; P trend = 0.285 for men and HR 1.49; 95% CI, 0.79-2.83; P trend = 0.942 for women). However, there was a significant increase in the risk for small cell carcinoma (HR 3.52; 95% CI, 1.49-8.28; P trend coffee is not associated with an increased risk of lung cancer incidence, despite observing a significant increase in the risk for small cell carcinoma.

  7. Metabolic Syndrome and Breast Cancer Risk.

    Science.gov (United States)

    Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

    2017-01-01

    The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.

  8. The influence of narrative risk communication on feelings of cancer risk.

    Science.gov (United States)

    Janssen, Eva; van Osch, Liesbeth; de Vries, Hein; Lechner, Lilian

    2013-05-01

    Evidence is accumulating for the importance of feelings of risk in explaining cancer preventive behaviours, but best practices for influencing these feelings are limited. The aim of this experimental study was to compare the effects of narrative and non-narrative risk communication about sunbed use on ease of imagination and feelings of cancer risk. A total of 233 female sunbed users in the general Dutch population were randomly assigned to one of three conditions: a narrative message (i.e., personal testimonial), a non-narrative cognitive message (i.e., factual risk information using cognitive-laden words), or a non-narrative affective message (i.e., factual risk information using affective-laden words). Ease of imagination and feelings of risk were assessed directly after the risk information was given (T1). Three weeks after the baseline session, feelings of risk were measured again (T2). The results revealed that sunbed users who were exposed to narrative risk information could better imagine themselves developing skin cancer and reported higher feelings of skin cancer risk at T1. Moreover, ease of imagination mediated the effects of message type on feelings of risk at T1 and T2. The findings provide support for the effects of narrative risk communication in influencing feelings of cancer risk through ease of imagination. Cancer prevention programmes may therefore benefit from including narrative risk information. Future research is important to investigate other mechanisms of narrative information and their most effective content and format. What is already known on this subject? Evidence is growing for the importance of feelings of risk in explaining cancer preventive behaviours. Narratives have increasingly been considered as an effective format for persuasive risk messages and studies have shown narrative risk communication to be effective in influencing cognitive risk beliefs. What does this study add? Increasing understanding of how feelings of cancer

  9. Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jin [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Qiang [Department of Hematology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jiandong [Department of Hepatobiliary Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Ren, Qinyou [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Cao, Wei [Department of Interventional Radiology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jingyue; Yu, Zhaocai [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yu, Fang [Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, Xi' an, Shaanxi (China); Wu, Yanlan [Department of Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Shi, Hengjun [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Wenchao [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China)

    2012-04-27

    A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

  10. Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

    International Nuclear Information System (INIS)

    Zheng, Jin; Liu, Qiang; Yang, Jiandong; Ren, Qinyou; Cao, Wei; Yang, Jingyue; Yu, Zhaocai; Yu, Fang; Wu, Yanlan; Shi, Hengjun; Liu, Wenchao

    2012-01-01

    A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells

  11. Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer

    Directory of Open Access Journals (Sweden)

    Timothy M. Pierpont

    2017-11-01

    Full Text Available Summary: Testicular germ cell tumors (TGCTs are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. : Using a mouse testicular germ cell tumor model, Pierpont et al. establish that male germ cells are susceptible to malignant transformation during a restricted window of embryonic development. The cancer stem cells of the resulting testicular cancers demonstrate genotoxin hypersensitivity, rendering these malignancies highly responsive to conventional chemotherapy. Keywords: testicular germ cell tumor, TGCT, cancer stem cells, CSCs, chemotherapy, embryonal carcinoma, EC, DNA damage response, DDR

  12. Risk of treatment-related esophageal cancer among breast cancer survivors

    DEFF Research Database (Denmark)

    Morton, L M; Gilbert, E S; Hall, P

    2012-01-01

    Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use.......Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use....

  13. Bricklayers and lung cancer risk

    NARCIS (Netherlands)

    Cremers, Jan

    2014-01-01

    The article ‘Lung cancer risk among bricklayers in a pooled analysis of case–control studies’ in the International Journal of Cancer publishes findings of an epidemiological study (in the frame of a SYNERGY-project) dedicated to the lung cancer risk among bricklayers. The authors conclude that a

  14. Maternal lung cancer and testicular cancer risk in the offspring.

    Science.gov (United States)

    Kaijser, Magnus; Akre, Olof; Cnattingius, Sven; Ekbom, Anders

    2003-07-01

    It has been hypothesized that smoking during pregnancy could increase the offspring's risk for testicular cancer. This hypothesis is indirectly supported by both ecological studies and studies of cancer aggregations within families. However, results from analytical epidemiological studies are not consistent, possibly due to methodological difficulties. To further study the association between smoking during pregnancy and testicular cancer, we did a population-based cohort study on cancer risk among offspring of women diagnosed with lung cancer. Through the use of the Swedish Cancer Register and the Swedish Second-Generation Register, we identified 8,430 women who developed lung cancer between 1958 and 1997 and delivered sons between 1941 and 1979. Cancer cases among the male offspring were then identified through the Swedish Cancer Register. Standardized incidence ratios were computed, using 95% confidence intervals. We identified 12,592 male offspring of mothers with a subsequent diagnosis of lung cancer, and there were 40 cases of testicular cancer (standardized incidence ratio, 1.90; 95% confidence interval, 1.35-2.58). The association was independent of maternal lung cancer subtype, and the risk of testicular cancer increased stepwise with decreasing time interval between birth and maternal lung cancer diagnosis. Our results support the hypothesis that exposure to cigarette smoking in utero increases the risk of testicular cancer.

  15. Squamous cell cancer (image)

    Science.gov (United States)

    Squamous cell cancer involves cancerous changes to the cells of the middle portion of the epidermal skin layer. It is ... malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It ...

  16. Prospectively Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort.

    Science.gov (United States)

    Pathak, Anand; Adams, Charleen D; Loud, Jennifer T; Nichols, Kathryn; Stewart, Douglas R; Greene, Mark H

    2015-10-01

    Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown. We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat. Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR = 11.9; 95% CI, 5.1-23.4; excess absolute risk = 7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR = 13.4; 95% CI, 1.6-48.6). Our data are the first to indicate that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer. Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies. ©2015 American Association for Cancer Research.

  17. Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    Robert Carreras-Torres

    Full Text Available Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR, or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR [95% confidence interval (CI] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00] for each standard deviation (SD increase in BMI [4.6 kg/m2], but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08] (Pheterogeneity = 4.3x10-3. Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3, providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl, while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l. Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results.Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.

  18. Induction of cancer stem cell properties in colon cancer cells by defined factors.

    Directory of Open Access Journals (Sweden)

    Nobu Oshima

    Full Text Available Cancer stem cells (CSCs are considered to be responsible for the dismal prognosis of cancer patients. However, little is known about the molecular mechanisms underlying the acquisition and maintenance of CSC properties in cancer cells because of their rarity in clinical samples. We herein induced CSC properties in cancer cells using defined factors. We retrovirally introduced a set of defined factors (OCT3/4, SOX2 and KLF4 into human colon cancer cells, followed by culture with conventional serum-containing medium, not human embryonic stem cell medium. We then evaluated the CSC properties in the cells. The colon cancer cells transduced with the three factors showed significantly enhanced CSC properties in terms of the marker gene expression, sphere formation, chemoresistance and tumorigenicity. We designated the cells with CSC properties induced by the factors, a subset of the transduced cells, as induced CSCs (iCSCs. Moreover, we established a novel technology to isolate and collect the iCSCs based on the differences in the degree of the dye-effluxing activity enhancement. The xenografts derived from our iCSCs were not teratomas. Notably, in contrast to the tumors from the parental cancer cells, the iCSC-based tumors mimicked actual human colon cancer tissues in terms of their immunohistological findings, which showed colonic lineage differentiation. In addition, we confirmed that the phenotypes of our iCSCs were reproducible in serial transplantation experiments. By introducing defined factors, we generated iCSCs with lineage specificity directly from cancer cells, not via an induced pluripotent stem cell state. The novel method enables us to obtain abundant materials of CSCs that not only have enhanced tumorigenicity, but also the ability to differentiate to recapitulate a specific type of cancer tissues. Our method can be of great value to fully understand CSCs and develop new therapies targeting CSCs.

  19. Industrial risk factors for colorectal cancer

    International Nuclear Information System (INIS)

    Lashner, B.A.; Epstein, S.S.

    1990-01-01

    Colorectal cancer is the second most common malignancy in the United States, and its incidence rates have sharply increased recently, especially in males. Industrial exposures, both occupational and environmental, are important colorectal cancer risk factors that are generally unrecognized by clinicians. Migration studies have documented that colorectal cancer is strongly associated with environmental risk factors. The causal role of occupational exposures is evidenced by a substantial literature associating specific work practices with increased colorectal cancer risks. Industrially related environmental exposures, including polluted drinking water and ionizing radiation, have also been associated with excess risks. Currently, there is a tendency to attribute colorectal cancer, largely or exclusively, to dietary and other lifestyle factors, thus neglecting these industrially related effects. Concerted efforts are needed to recognize the causal role of industrial risk factors and to encourage government and industry to reduce carcinogenic exposures. Furthermore, cost-effective screening programs for high-risk population groups are critically needed to further reduce deaths from colorectal cancer. 143 references

  20. Risks for skin and other cancers up to 25 years after burn injuries

    DEFF Research Database (Denmark)

    Mellemkjaer, Lene; Hölmich, Lisbet R; Gridley, Gloria

    2006-01-01

    BACKGROUND: Malignant degeneration of chronic ulcers such as nonhealed burn wounds has been described in the literature, but this phenomenon has never been quantified in an epidemiologic study. We investigated the risks for skin and other cancers among patients with a prior burn. METHODS: We...... with that in the general population of Denmark. RESULTS: Patients with burn had 139 skin cancers, with 189 expected, yielding a standardized incidence ratio of 0.7 (95% confidence interval = 0.6-0.9). This reduced risk was due mainly to deficits of basal cell carcinoma and malignant melanoma, whereas the number...... of squamous cell carcinomas observed was close to expected. We saw no consistent increases in risk for skin cancer in the subgroups of patients with the most severe injuries or with the longest periods of follow up. CONCLUSIONS: The tendency to malignant degeneration of burn scars, described in previous...

  1. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  2. Obesity, physical activity and cancer risks: Results from the Cancer, Lifestyle and Evaluation of Risk Study (CLEAR).

    Science.gov (United States)

    Nunez, Carlos; Bauman, Adrian; Egger, Sam; Sitas, Freddy; Nair-Shalliker, Visalini

    2017-04-01

    Physical activity (PA) has been associated with lower risk of cardiovascular diseases, but the evidence linking PA with lower cancer risk is inconclusive. We examined the independent and interactive effects of PA and obesity using body mass index (BMI) as a proxy for obesity, on the risk of developing prostate (PC), postmenopausal breast (BC), colorectal (CRC), ovarian (OC) and uterine (UC) cancers. We estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for cancer specific confounders, in 6831 self-reported cancer cases and 1992 self-reported cancer-free controls from the Cancer Lifestyle and Evaluation of Risk Study, using unconditional logistic regression. For women, BMI was positively associated with UC risk; specifically, obese women (BMI≥30kg/m 2 ) had nearly twice the risk of developing UC compared to women with healthy-BMI-range (risk of developing any cancer type, CRC and PC. In particular, obese men had 37% (OR=1.37;CI:1.11-1.70), 113% (OR=2.13;CI:1.55-2.91) and 51% (OR=1.51;CI:1.17-1.94) higher risks of developing any cancer, CRC and PC respectively, when compared to men with healthy-BMI-range (BMIrisks of CRC, UC and BC. In particular, the highest level of PA (versus nil activity) was associated with reduced risks of CRC (OR=0.60;CI:0.44-0.84) and UC (OR=0.47;CI:0.27-0.80). Reduced risks of BC were associated with low (OR=0.66;CI:0.51-0.86) and moderate (OR=0.72;CI:0.57-0.91) levels of PA. There was no association between PA levels and cancer risks for men. We found no evidence of an interaction between BMI and PA in the CLEAR study. These findings suggest that PA and obesity are independent cancer risk factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Cell phones and cancer

    Science.gov (United States)

    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of ...

  4. Variations in the NBN/NBS1 gene and the risk of breast cancer in non-BRCA1/2 French Canadian families with high risk of breast cancer

    International Nuclear Information System (INIS)

    Desjardins, Sylvie; Beauparlant, Joly Charles; Labrie, Yvan; Ouellette, Geneviève; INHERIT BRCAs; Durocher, Francine

    2009-01-01

    The Nijmegen Breakage Syndrome is a chromosomal instability disorder characterized by microcephaly, growth retardation, immunodeficiency, and increased frequency of cancers. Familial studies on relatives of these patients indicated that they also appear to be at increased risk of cancer. In a candidate gene study aiming at identifying genetic determinants of breast cancer susceptibility, we undertook the full sequencing of the NBN gene in our cohort of 97 high-risk non-BRCA1 and -BRCA2 breast cancer families, along with 74 healthy unrelated controls, also from the French Canadian population. In silico programs (ESEfinder, NNSplice, Splice Site Finder and MatInspector) were used to assess the putative impact of the variants identified. The effect of the promoter variant was further studied by luciferase gene reporter assay in MCF-7, HEK293, HeLa and LNCaP cell lines. Twenty-four variants were identified in our case series and their frequency was further evaluated in healthy controls. The potentially deleterious p.Ile171Val variant was observed in one case only. The p.Arg215Trp variant, suggested to impair NBN binding to histone γ-H2AX, was observed in one breast cancer case and one healthy control. A promoter variant c.-242-110delAGTA displayed a significant variation in frequency between both sample sets. Luciferase reporter gene assay of the promoter construct bearing this variant did not suggest a variation of expression in the MCF-7 breast cancer cell line, but indicated a reduction of luciferase expression in both the HEK293 and LNCaP cell lines. Our analysis of NBN sequence variations indicated that potential NBN alterations are present, albeit at a low frequency, in our cohort of high-risk breast cancer cases. Further analyses will be needed to fully ascertain the exact impact of those variants on breast cancer susceptibility, in particular for variants located in NBN promoter region

  5. Risks of Skin Cancer Screening

    Science.gov (United States)

    ... factors increase or decrease the risk of skin cancer. Skin cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about skin cancer: Skin Cancer Prevention Skin Cancer Treatment Melanoma Treatment Genetics ...

  6. Myastenia and risk of cancer

    DEFF Research Database (Denmark)

    Pedersen, Emil Arnspang; Pottegård, Anton; Hallas, Jesper

    2014-01-01

    BACKGROUND AND PURPOSE: To evaluate the association between having non-thymoma myasthenia and the risk of extra-thymic cancer in a population-based setting. METHODS: A nationwide case-control study was conducted in Denmark based on medical registries. The study included all cases with a first time...... diagnosis of cancer during 2000-2009. Each case was matched by birth year and gender with eight population controls using risk set sampling. Subjects with myasthenia were identified through a validated register-based algorithm. Conditional logistic regression was used to compute crude and adjusted odds...... risk of overall cancer (OR 1.1; 95% CI 0.9-1.4). Adjusted ORs for major cancer sites were also close to unity, whereas an elevated risk of lymphomas was observed (OR 2.0; 95% CI 0.8-5.5). Early-onset myasthenia was associated with a slightly increased OR for overall cancer (1.5; 95% CI 1...

  7. Classification and risk assessment of individuals with familial polyposis, Gardner's syndrome, and familial non-polyposis colon cancer from [3H]thymidine labeling patterns in colonic epithelial cells

    International Nuclear Information System (INIS)

    Lipkin, M.; Blattner, W.A.; Gardner, E.J.; Burt, R.W.; Lynch, H.; Deschner, E.; Winawer, S.; Fraumeni, J.F. Jr.

    1984-01-01

    A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. The analysis is based on the microautoradiographic observation of [ 3 H]thymidine-labeled epithelial cells in colonic mucosa of the kindred members. From biopsies of colonic mucosa which are labeled with [ 3 H]thymidine in vitro, the degree of similarity of each subject's cell-labeling pattern measured over entire crypts was automatically compared to the labeling patterns of high-risk and low-risk reference populations. Each individual was then presumptively classified and assigned to one of the reference populations, and a degree of risk for the classification was provided. In carrying out the analysis, a linear score was calculated for each individual relative to each of the reference populations, and the classification was based on the polarity of the score difference; the degree of risk was then quantitated from the magnitude of the score difference. When the method was applied to kindreds having either familial polyposis or familial non-polyposis colon cancer, it effectively segregated individuals affected with disease from others at low risk, with sensitivity and specificity ranging from 71 to 92%. Further application of the method to asymptomatic family members believed to be at 50% risk on the basis of pedigree evaluation revealed a biomodal distribution to nearly zero or full risk. The accuracy and simplicity of this approach and its capability of revealing early stages of abnormal colonic epithelial cell development indicate potential for preclinical screening of subjects at risk in cancer-prone kindreds and for assisting the analysis of modes of inheritance

  8. Emotional, Biological, and Cognitive Impact of a Brief Expressive Writing Intervention for Women at Familial Breast Cancer Risk

    National Research Council Canada - National Science Library

    Valdimarsdottir, Heiddis

    2006-01-01

    Women at familial breast cancer risk have highly inflated perceptions of their risk of developing the disease high levels of cancer-specific distress and lower levels of natural killer cell activity (NKCA...

  9. Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer.

    Science.gov (United States)

    Pierpont, Timothy M; Lyndaker, Amy M; Anderson, Claire M; Jin, Qiming; Moore, Elizabeth S; Roden, Jamie L; Braxton, Alicia; Bagepalli, Lina; Kataria, Nandita; Hu, Hilary Zhaoxu; Garness, Jason; Cook, Matthew S; Capel, Blanche; Schlafer, Donald H; Southard, Teresa; Weiss, Robert S

    2017-11-14

    Testicular germ cell tumors (TGCTs) are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Women with family cancer history are at risk for poorer physical quality of life and lower self-efficacy: a longitudinal study among men and women with non-small cell lung cancer.

    Science.gov (United States)

    Banik, Anna; Schwarzer, Ralf; Pawlowska, Izabela; Boberska, Monika; Cieslak, Roman; Luszczynska, Aleksandra

    2017-04-04

    We investigated the determinants of trajectories of physical symptoms related to lung cancer (a quality of life [QOL] aspect) and self-efficacy among patients with non-small cell lung cancer (NSCLC). It was hypothesized that gender and family cancer history in first-degree relatives would have synergistic effects on QOL-lung cancer specific symptoms and self-efficacy. Women with family cancer history were expected to be at risk of poorer adjustment. Quantitative, longitudinal design was applied. Participants provided their responses at 3-4 days after surgery, 1-month follow-up, and 4-month follow-up. We recruited 102 in-patients (men: 51%) with NSCLC who underwent surgery aimed at removing a lung tumor. Self-report data were collected with QLQ-LC13 and a scale for self-efficacy for managing illness. Mixed-models analysis indicated that trajectories of physical quality of life (symptoms of lung cancer) as well as self-efficacy were unfavorable among women with family cancer history. Among NSCLC patients, gender and family cancer history may be considered basic screening criteria for identifying groups of patients at risk for poorer physical QOL (higher level of physical symptoms related to lung cancer) and lower incline of self-efficacy after cancer surgery.

  11. Cancer stem cell markers in common cancers - therapeutic implications

    DEFF Research Database (Denmark)

    Klonisch, Thomas; Wiechec, Emilia; Hombach-Klonisch, Sabine

    2008-01-01

    Rapid advance in the cancer stem cell field warrants optimism for the development of more reliable cancer therapies within the next 2-3 decades. Below, we characterize and compare the specific markers that are present on stem cells, cancer cells and cancer stem cells (CSC) in selected tissues...

  12. Korean risk assessment model for breast cancer risk prediction.

    Science.gov (United States)

    Park, Boyoung; Ma, Seung Hyun; Shin, Aesun; Chang, Myung-Chul; Choi, Ji-Yeob; Kim, Sungwan; Han, Wonshik; Noh, Dong-Young; Ahn, Sei-Hyun; Kang, Daehee; Yoo, Keun-Young; Park, Sue K

    2013-01-01

    We evaluated the performance of the Gail model for a Korean population and developed a Korean breast cancer risk assessment tool (KoBCRAT) based upon equations developed for the Gail model for predicting breast cancer risk. Using 3,789 sets of cases and controls, risk factors for breast cancer among Koreans were identified. Individual probabilities were projected using Gail's equations and Korean hazard data. We compared the 5-year and lifetime risk produced using the modified Gail model which applied Korean incidence and mortality data and the parameter estimators from the original Gail model with those produced using the KoBCRAT. We validated the KoBCRAT based on the expected/observed breast cancer incidence and area under the curve (AUC) using two Korean cohorts: the Korean Multicenter Cancer Cohort (KMCC) and National Cancer Center (NCC) cohort. The major risk factors under the age of 50 were family history, age at menarche, age at first full-term pregnancy, menopausal status, breastfeeding duration, oral contraceptive usage, and exercise, while those at and over the age of 50 were family history, age at menarche, age at menopause, pregnancy experience, body mass index, oral contraceptive usage, and exercise. The modified Gail model produced lower 5-year risk for the cases than for the controls (p = 0.017), while the KoBCRAT produced higher 5-year and lifetime risk for the cases than for the controls (pKorean women, especially urban women.

  13. Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

    Science.gov (United States)

    Mierke, Claudia T.

    There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

  14. Risk Factors of Cancer in the United Arab Emirates.

    Science.gov (United States)

    Razzak, Hira Abdul; Harbi, Alya; Shelpai, Wael; Qawas, xAhmadxx

    2018-01-01

    Cancer is recognized to be a major healthcare problem globally. Cancer is a disease that mainly occurs when alterations in a normal cell group within the body leads to uncontrolled growth, mainly causing a lump referred to as a tumor. The aim of this study is to systematically review and extract studies reporting the risk factors of cancer in UAE between 2007 and 2016. A systematic literature search was performed by using "PubMed, Scopus databases, Science direct, and local journals" and appropriate key terms to retrieve studies carried out in United Arab Emirates with regards to risk factors of the cancer. 75 articles were extracted in the beginning. After screening for exclusion criteria and retrieval of full texts, overall 16 articles were used in this study. Search limits were restricted to studies in English language, between 2007 and 2016, and on UAE population (both citizens and expatriates). This review yielded 16 studies about the cancer risk factors in United Arab Emirates, including cross sectional studies (n = 9), population-based crosssectional retrospective survey (n = 1), retrospective cohort studies (n = 4) and qualitative studies (n = 2). Tobacco use, unhealthy diet, family history, infection with HPV, physical activity, and radiation exposure were among the factors investigated. There was insufficient evidence available on some potentially essential risk factors such as use of alcohol, aging, and being overweight. This systematic review signifies an increasing cancer prevalence in the United Arab Emirates and suggests that extra effort is needed with a multi-sectorial approach in future at both the national and international level to effectively tackle the burden of cancer.

  15. Treatment recommendations in patients diagnosed with high-risk cutaneous squamous cell carcinoma

    International Nuclear Information System (INIS)

    Veness, M.J.

    2005-01-01

    Non-melanoma cutaneous cancers occur at an epidemic rate in Australia. With an ageing population, more Australians will develop these cancers and at an increasing rate. In the majority of cases local treatment is highly curative. However, a subset of the population will be diagnosed with a high-risk cutaneous squamous cell carcinoma. These can be defined as patients at risk of having subclinical metastases to regional lymph nodes based on unfavourable primary lesion features (including inadequately excised and recurrent lesions), patients with metastatic squamous cell carcinoma to regional lymph nodes, and squamous cell carcinoma in immunosuppressed patients. The mortality and morbidity associated with high-risk cutaneous squamous cell carcinoma is usually as a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Radiotherapy has an essential role in treating these patients and in many cases the addition of adjuvant radiotherapy may be life saving. It is therefore important that all clinicians treating skin cancers have an understanding and awareness of the optimal approach to these patients. The aim of this article is to present treatment recommendations based on an overview of the current published literature. Copyright (2005) Blackwell Science Pty Ltd

  16. Risks of Breast Cancer Screening

    Science.gov (United States)

    ... is small. Different factors increase or decrease the risk of breast cancer. Anything that increases your chance ... magnetic resonance imaging) in women with a high risk of breast cancer MRI is a procedure that ...

  17. Risks of Lung Cancer Screening

    Science.gov (United States)

    ... in women. Different factors increase or decrease the risk of lung cancer. Anything that increases your chance ... been studied to see if they decrease the risk of dying from lung cancer. The following screening ...

  18. Risks of Endometrial Cancer Screening

    Science.gov (United States)

    ... Health history and certain medicines can affect the risk of developing endometrial cancer. Anything that increases your ... have abnormal vaginal bleeding, check with your doctor. Risks of Endometrial Cancer Screening Key Points Screening tests ...

  19. Risks of Esophageal Cancer Screening

    Science.gov (United States)

    ... alcohol use, and Barrett esophagus can affect the risk of developing esophageal cancer. Anything that increases the ... tissue gives off less light than normal tissue. Risks of Esophageal Cancer Screening Key Points Screening tests ...

  20. Risks of Cervical Cancer Screening

    Science.gov (United States)

    ... women. Human papillomavirus (HPV) infection is the major risk factor for cervical cancer. Although most women with ... clinical trials is available from the NCI website . Risks of Cervical Cancer Screening Key Points Screening tests ...

  1. Increased risk of histologically defined cancer subtypes in human immunodeficiency virus-infected individuals: clues for possible immunosuppression-related or infectious etiology.

    Science.gov (United States)

    Shiels, Meredith S; Engels, Eric A

    2012-10-01

    Malignancies that occur in excess among human immunodeficiency virus (HIV)-infected individuals may be caused by immunosuppression or infections. Because histologically defined cancer subtypes have not been systematically evaluated, their risk was assessed among people with acquired immunodeficiency syndrome (AIDS). Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 US population-based HIV/AIDS and cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies), and time since onset of AIDS (a proxy of immunosuppression). Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T cell leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia, and myeloid leukemias. For several of these cancer subtypes, significant declines in SIRs were observed across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since onset of AIDS (ie, prolonged immunosuppression). The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents. Copyright © 2012 American Cancer Society.

  2. Risks of Liver (Hepatocellular) Cancer Screening

    Science.gov (United States)

    ... cancer. Having hepatitis or cirrhosis can increase the risk of developing liver cancer. Anything that increases the ... clinical trials is available from the NCI website . Risks of Liver (Hepatocellular) Cancer Screening Key Points Screening ...

  3. Targeting cancer cells using 3-bromopyruvate for selective cancer treatment

    Directory of Open Access Journals (Sweden)

    Hussam H Baghdadi

    2017-01-01

    Full Text Available Cancer treatment deserves more research efforts despite intensive conventional treatment modalities for many types of malignancies. Metastasis and resistance to chemotherapy and radiotherapy receive a lot of global research efforts. The current advances in cancer biology may improve targeting the critical metabolic differences that distinguish cancer cells from normal cells. Cancer cells are highly glycolytic for energy production, exhibit the Warburg effect, establish aggressive acidic microenvironment, maintain cancer stem cells, exhibit resistance to chemotherapy, have low antioxidant systems but different ΔΨm (delta psi, mitochondrial transmembrane potential, express P-glycoprotein for multidrug resistance, upregulate glucose transporters and monocarboxylate transporters and are under high steady-state reactive oxygen species conditions. Normal cells differ in all these aspects. Lactate produced through the Warburg effect helps cancer metastasis. Targeting glycolysis reactions for energy production in cancer cells seems promising in decreasing the proliferation and metastasis of cancer cells. 3-bromopyruvate makes use of cancer biology in treating cancer cells, cancer stem cells and preventing metastasis in human cancer as discussed in this review. Updated advances are analyzed here, which include research analysis of background, experience, readings in the field of cancer biology, oncology and biochemistry.

  4. Increased stomach cancer risk following radiotherapy for testicular cancer

    DEFF Research Database (Denmark)

    Hauptmann, M; Fossa, S D; Stovall, M

    2015-01-01

    BACKGROUND: Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse. METHODS: In a cohort of 22,269 5-year TC survivors diagnosed during 1959-1987, doses to stomach subsites were estimated...... for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression. RESULTS: Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received...... radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7-20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose (P-trend

  5. Pancreatic cancer risk in hereditary pancreatitis

    OpenAIRE

    Weiss, Frank U.

    2014-01-01

    Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic...

  6. Contribution of ARLTS1 Cys148Arg (T442C variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Sanna Siltanen

    Full Text Available ARLTS1 is a recently characterized tumor suppressor gene at 13q14.3, a region frequently deleted in both sporadic and hereditary prostate cancer (PCa. ARLTS1 variants, especially Cys148Arg (T442C, increase susceptibility to different cancers, including PCa. In this study the role of Cys148Arg substitution was investigated as a risk factor for PCa using both genetic and functional analysis. Cys148Arg genotypes and expression of the ARLTS1 were explored in a large set of familial and unselected PCa cases, clinical tumor samples, xenografts, prostate cancer cell lines and benign prostatic hyperplasia (BPH samples. The frequency of the variant genotype CC was significantly higher in familial (OR = 1.67, 95% CI = 1.08-2.56, P = 0.019 and unselected patients (OR = 1.52, 95% CI = 1.18-1.97, P = 0.001 and the overall risk was increased (OR = 1.54, 95% CI = 1.20-1.98, P = 0.0007. Additional analysis with clinicopathological data revealed an association with an aggressive disease (OR = 1.28, 95% CI = 1.05-∞, P = 0.02. The CC genotype of the Cys148Arg variant was also contributing to the lowered ARLTS1 expression status in lymphoblastoid cells from familial patients. In addition significantly lowered ARLTS1 expression was observed in clinical tumor samples compared to BPH samples (P = 0.01. The ARLTS1 co-expression signature based on previously published microarray data was generated from 1587 cancer samples confirming the low expression of ARLTS1 in PCa and showed that ARLTS1 expression was strongly associated with immune processes. This study provides strong confirmation of the important role of ARLTS1 Cys148Arg variant as a contributor in PCa predisposition and a potential marker for aggressive disease outcome.

  7. The theoretical risk of non-melanoma skin cancer from environmental radon exposure

    International Nuclear Information System (INIS)

    Eatough, J.P.; Henshaw, D.L.

    1995-01-01

    The skin cancer risk theoretically attributable to radon associated alpha particle radiation is calculated on the basis of recent dosimetry, and published radiation risk factors. The results suggest that of the order of 2% (range 1%-10%) of non-melanoma skin cancers in the UK may be associated with radon exposure at the average UK radon concentration of 20 Bq m -3 . The range quoted is due solely to uncertainties in the estimate of the radon dose to the basal layer of the skin, and additional sources of uncertainty are discussed. The estimate is dependent on the assumption that the target cells for radiation induced skin cancer lie in the basal layer of the epidermis, and that irradiation of the dermis is not necessary for skin cancer induction. Due to the effect of ultraviolet radiation on the risk factors for ionising radiation, ultraviolet radiation exposure must also be involved in the induction of the majority of any skin cancer cases linked to radon exposure. (author)

  8. Cancer stem cells and differentiation therapy.

    Science.gov (United States)

    Jin, Xiong; Jin, Xun; Kim, Hyunggee

    2017-10-01

    Cancer stem cells can generate tumors from only a small number of cells, whereas differentiated cancer cells cannot. The prominent feature of cancer stem cells is its ability to self-renew and differentiate into multiple types of cancer cells. Cancer stem cells have several distinct tumorigenic abilities, including stem cell signal transduction, tumorigenicity, metastasis, and resistance to anticancer drugs, which are regulated by genetic or epigenetic changes. Like normal adult stem cells involved in various developmental processes and tissue homeostasis, cancer stem cells maintain their self-renewal capacity by activating multiple stem cell signaling pathways and inhibiting differentiation signaling pathways during cancer initiation and progression. Recently, many studies have focused on targeting cancer stem cells to eradicate malignancies by regulating stem cell signaling pathways, and products of some of these strategies are in preclinical and clinical trials. In this review, we describe the crucial features of cancer stem cells related to tumor relapse and drug resistance, as well as the new therapeutic strategy to target cancer stem cells named "differentiation therapy."

  9. Pre-cancer risk assessment in habitual smokers from DIC images of oral exfoliative cells using active contour and SVM analysis.

    Science.gov (United States)

    Dey, Susmita; Sarkar, Ripon; Chatterjee, Kabita; Datta, Pallab; Barui, Ananya; Maity, Santi P

    2017-04-01

    Habitual smokers are known to be at higher risk for developing oral cancer, which is increasing at an alarming rate globally. Conventionally, oral cancer is associated with high mortality rates, although recent reports show the improved survival outcomes by early diagnosis of disease. An effective prediction system which will enable to identify the probability of cancer development amongst the habitual smokers, is thus expected to benefit sizable number of populations. Present work describes a non-invasive, integrated method for early detection of cellular abnormalities based on analysis of different cyto-morphological features of exfoliative oral epithelial cells. Differential interference contrast (DIC) microscopy provides a potential optical tool as this mode provides a pseudo three dimensional (3-D) image with detailed morphological and textural features obtained from noninvasive, label free epithelial cells. For segmentation of DIC images, gradient vector flow snake model active contour process has been adopted. To evaluate cellular abnormalities amongst habitual smokers, the selected morphological and textural features of epithelial cells are compared with the non-smoker (-ve control group) group and clinically diagnosed pre-cancer patients (+ve control group) using support vector machine (SVM) classifier. Accuracy of the developed SVM based classification has been found to be 86% with 80% sensitivity and 89% specificity in classifying the features from the volunteers having smoking habit. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. The combined risks of reduced or increased function variants in cell death pathway genes differentially influence cervical cancer risk and herpes simplex virus type 2 infection among black Africans and the Mixed Ancestry population of South Africa

    International Nuclear Information System (INIS)

    Chattopadhyay, Koushik; Williamson, Anna-Lise; Hazra, Annapurna; Dandara, Collet

    2015-01-01

    Cervical cancer is one of the most important cancers worldwide with a high incident and mortality rate and is caused by the human papilloma virus (HPV). Among sexually active women who get infected with human papillomavirus (HPV), a small fraction progresses to cervical cancer disease pointing to possible roles of additional risk factors in development of the disease which include host genetic factors and other infections such as HSV-2. Since cellular apoptosis plays a role in controlling the spread of virus-infections in cells, gene variants altering the function of proteins involved in cell death pathways might be associated with the clearing of virus infections. Activity altering polymorphisms in FasR (−1377G > A and -670A > G), FasL (−844 T > C) and CASP8 (−652 6 N ins/del) genes have been shown to alter the mechanism of apoptosis by modifying the level of expression of their correspondent proteins. In the present study, we set out to investigate the combined risks of CASP8, FasR, and FasL polymorphisms in cervical cancer, pre-cancerous lesions, HPV infection and HSV-2 infection. Participants were 442 South African women of black African and mixed-ancestry origin with invasive cervical cancer and 278 control women matched by age, ethnicity and domicile status. FasR and FasL polymorphisms were genotyped by TaqMan and CASP8 polymorphism by PCR-RFLP. The results were analysed with R using haplo.stats software version 1.5.2. CASP8 -652 6 N del + FasR-670A was associated with a reduced risk (P = 0.019, Combined Polymorphism Score (CPS) = −2.34) and CASP8 -652 6 N ins + FasR-1377G was associated with a marginal increased risk (P = 0.047, CPS = 1.99) of cervical cancer among black Africans. When compared within the control group, CASP8 -652 6 N ins + FasR-1377A showed a reduced risk (P = 0.023, CPS = −2.28) of HSV-2 infection in both black African and mixed-ancestry population. Our results show that the combined risks of variants in cell death pathway genes

  11. The combined risks of reduced or increased function variants in cell death pathway genes differentially influence cervical cancer risk and herpes simplex virus type 2 infection among black Africans and the Mixed Ancestry population of South Africa.

    Science.gov (United States)

    Chattopadhyay, Koushik; Williamson, Anna-Lise; Hazra, Annapurna; Dandara, Collet

    2015-10-12

    Cervical cancer is one of the most important cancers worldwide with a high incident and mortality rate and is caused by the human papilloma virus (HPV). Among sexually active women who get infected with human papillomavirus (HPV), a small fraction progresses to cervical cancer disease pointing to possible roles of additional risk factors in development of the disease which include host genetic factors and other infections such as HSV-2. Since cellular apoptosis plays a role in controlling the spread of virus-infections in cells, gene variants altering the function of proteins involved in cell death pathways might be associated with the clearing of virus infections. Activity altering polymorphisms in FasR (-1377G > A and -670A > G), FasL (-844 T > C) and CASP8 (-652 6 N ins/del) genes have been shown to alter the mechanism of apoptosis by modifying the level of expression of their correspondent proteins. In the present study, we set out to investigate the combined risks of CASP8, FasR, and FasL polymorphisms in cervical cancer, pre-cancerous lesions, HPV infection and HSV-2 infection. Participants were 442 South African women of black African and mixed-ancestry origin with invasive cervical cancer and 278 control women matched by age, ethnicity and domicile status. FasR and FasL polymorphisms were genotyped by TaqMan and CASP8 polymorphism by PCR-RFLP. The results were analysed with R using haplo.stats software version 1.5.2. CASP8 -652 6 N del + FasR-670A was associated with a reduced risk (P = 0.019, Combined Polymorphism Score (CPS) = -2.34) and CASP8 -652 6 N ins + FasR-1377G was associated with a marginal increased risk (P = 0.047, CPS = 1.99) of cervical cancer among black Africans. When compared within the control group, CASP8 -652 6 N ins + FasR-1377A showed a reduced risk (P = 0.023, CPS = -2.28) of HSV-2 infection in both black African and mixed-ancestry population. Our results show that the combined risks of

  12. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

  13. Thyroid Cancer Risk Assessment Tool

    Science.gov (United States)

    The R package thyroid implements a risk prediction model developed by NCI researchers to calculate the absolute risk of developing a second primary thyroid cancer (SPTC) in individuals who were diagnosed with a cancer during their childhood.

  14. Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database.

    Science.gov (United States)

    Wei, Shenhai; Tian, Jintao; Song, Xiaoping; Wu, Bingqun; Liu, Limin

    2018-01-01

    To investigate the probability of death (POD) from any causes by time after diagnosis of non-small cell lung cancer (NSCLC) and the factors associated with survival for NSCLC patients. A total of 202,914 patients with NSCLC from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) and lung cancer-specific survival (LCSS) were calculated and POD from any causes at different time periods after diagnosis was explored. The predictive factors for OS, LCSS and survival from non-lung cancer deaths were investigated using multivariate analysis with Cox proportional hazards regression and competing risk regression analysis. The 5- and 10-year OS were 20.4% and 11.5%, accordingly that for LCSS were 25.5% and 18.4%, respectively. Lung cancer contributed 88.3% (n = 128,402) of the deaths. The POD from lung cancer decreased with time after diagnosis. In multivariate analysis, advanced age and advanced stage of NSCLC were associated with decreased OS and LCSS. Comparing to no surgery, any kind of resection conferred lower risk of death from lung cancer and higher risk of dying from non-lung cancer conditions except lobectomy or bilobectomy, which was associated with lower risk of death from both lung cancer and non-lung cancer conditions. Most of the patients with NSCLC died from lung cancer. Rational surveillance and treatment policies should be made for them. Early stage and lobectomy or bilobectomy were associated with improved OS and LCSS. It is reasonable to focus on early detection and optimal surgical treatment for NSCLC.

  15. Label-free single-cell separation and imaging of cancer cells using an integrated microfluidic system

    DEFF Research Database (Denmark)

    Antfolk, Maria; Kim, Soo Hyeon; Koizumi, Saori

    2017-01-01

    , an integrated system is presented that efficiently eliminates this risk by integrating label-free separation with single cell arraying of the target cell population, enabling direct on-chip tumor cell identification and enumeration. Prostate cancer cells (DU145) spiked into a sample with whole blood...... a fully integrated system for rapid label-free separation and on-chip phenotypic characterization of circulating tumor cells from peripheral venous blood in clinical practice....

  16. Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Vinayak Muralidhar

    2016-02-01

    Full Text Available Purpose : Recent retrospective data suggest that brachytherapy (BT boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA 20 ng/ml. Material and methods: We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results : EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258, and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270. Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022. Conclusions : Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease.

  17. Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer

    Directory of Open Access Journals (Sweden)

    Bravo-Cuellar Alejandro

    2008-04-01

    Full Text Available Abstract Background Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95 in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. Methods Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma. The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L were measured by ELISA kits. Results We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. Conclusion Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of

  18. Risk of cancer among HIV-infected individuals compared to the background population

    DEFF Research Database (Denmark)

    Helleberg, Marie; Gerstoft, Jan; Afzal, Shoaib

    2014-01-01

    BACKGROUND: The relative impact of immune deficiency and lifestyle-related factors on risk of cancer in the HIV-infected population is controversial. We aimed to estimate the population-attributable fractions (PAFs) associated with smoking, being HIV-infected and with immune deficiency. METHODS...... of cancer associated with smoking and with being HIV-infected were 27 and 49%, respectively. For cancers not strongly related to smoking or viral infections, the PAFs associated with being HIV-infected and with immune deficiency were 0%. CONCLUSION: The risk of cancer is increased in HIV patients compared......: In a Danish, nationwide, population-based cohort study (1995-2011), incidences of cancer were compared between an HIV-infected cohort and a population-based matched cohort in analyses stratified on cancer category, smoking status and for HIV patients: low CD4 cell count. RESULTS: We included 3503 HIV patients...

  19. An abuse of risk assessment: how regulatory agencies improperly adopted LNT for cancer risk assessment.

    Science.gov (United States)

    Calabrese, Edward J

    2015-04-01

    The Genetics Panel of the National Academy of Sciences' Committee on Biological Effects of Atomic Radiation (BEAR) recommended the adoption of the linear dose-response model in 1956, abandoning the threshold dose-response for genetic risk assessments. This recommendation was quickly generalized to include somatic cells for cancer risk assessment and later was instrumental in the adoption of linearity for carcinogen risk assessment by the Environmental Protection Agency. The Genetics Panel failed to provide any scientific assessment to support this recommendation and refused to do so when later challenged by other leading scientists. Thus, the linearity model used in cancer risk assessment was based on ideology rather than science and originated with the recommendation of the NAS BEAR Committee Genetics Panel. Historical documentation in support of these conclusions is provided in the transcripts of the Panel meetings and in previously unexamined correspondence among Panel members.

  20. Epidemiology, molecular epidemiology, and risk factors for renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Chiara Paglino

    2011-12-01

    Full Text Available Despite only accounting for approximately 2% of all new primary cancer cases, renal cell carcinoma (RCC incidence has dramatically increased over time. Incidence rates vary greatly according to geographic areas, so that it is extremely likely that exogenous risk factors could play an important role in the development of this cancer. Several risk factors have been linked with RCC, including cigarette smoking, obesity, hypertension (and antihypertensive drugs, chronic kidney diseases (also dialysis and transplantation, as well as the use of certain analgesics. Furthermore, although RCC has not generally been considered an occupational cancer, several types of occupationally-derived exposures have been implicated in its pathogenesis. These include exposure to asbestos, chlorinated solvents, gasoline, diesel exhaust fumes, polycyclic aromatic hydrocarbons, printing inks and dyes, cadmium and lead. Finally, families with a predisposition to the development of renal neoplasms were identified and the genes involved discovered and characterized. Therefore, there are now four well-characterized, genetically determined syndromes associated with an increased incidence of kidney tumors, i.e., Von Hippel Lindau (VHL, Hereditary Papillary Renal Carcinoma (HPRC, Birt-Hogg-Dubé Syndrome (BHD, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC. This review will address present knowledge about the epidemiology, molecular epidemiology and risk factors of RCC.

  1. The diagnostic impact of testicular biopsies for intratubular germ cell neoplasia in cryptorchid boys and the subsequent risk of testicular cancer in men with prepubertal surgery for syndromic or non-syndromic cryptorchidism

    DEFF Research Database (Denmark)

    Osterballe, Lene; Clasen-Linde, Erik; Cortes, Dina

    2017-01-01

    INTRODUCTION: Cryptorchidism is a risk factor for testicular cancer in adult life. It remains unclear how prepubertal surgery for cryptorchidism impacts later development of adult testicular cancer. The aim of study was to investigate tools to identify the cryptorchid boys who later develop...... testicular cancer. METHODS: The study cohort consisted of 1403 men operated prepubertally/pubertally for undescended testis between 1971 and 2003. At surgery testicular biopsies were taken from the cryptorchid testes. The boys were followed for occurrence of testicular cancer. The testicular cancer risk...... was compared to the risk in the Danish Population. Testicular biopsies from the boys who developed testicular cancer during follow-up underwent histological examination with specific diagnostic immunohistochemical markers for germ cell neoplasia. RESULTS: The cohort was followed for 33,627 person years at risk...

  2. Indomethacin Inhibits Cancer Cell Migration via Attenuation of Cellular Calcium Mobilization

    Directory of Open Access Journals (Sweden)

    Ke-Li Tsai

    2013-06-01

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes formation. Furthermore, endothelial growth factor (EGF-mediated Ca2+ influx was attenuated by indomethacin in a dose dependent manner. Our results identified a new mechanism of action for indomethacin: inhibition of calcium influx that is a key determinant of cancer cell migration.

  3. Genetic Variants in the Wnt/β-Catenin Signaling Pathway as Indicators of Bladder Cancer Risk.

    Science.gov (United States)

    Pierzynski, Jeanne A; Hildebrandt, Michelle A; Kamat, Ashish M; Lin, Jie; Ye, Yuanqing; Dinney, Colin P N; Wu, Xifeng

    2015-12-01

    Genetic factors that influence bladder cancer risk remain largely unknown. Previous research has suggested that there is a strong genetic component underlying the risk of bladder cancer. The Wnt/β-catenin signaling pathway is a key modulator of cellular proliferation through its regulation of stem cell homeostasis. Furthermore, variants in the Wnt/β-catenin signaling pathway have been implicated in the development of other cancers, leading us to believe that this pathway may have a vital role in bladder cancer development. A total of 230 single nucleotide polymorphisms in 40 genes in the Wnt/β-catenin signaling pathway were genotyped in 803 bladder cancer cases and 803 healthy controls. A total of 20 single nucleotide polymorphisms were nominally significant for risk. Individuals with 2 variants of LRP6: rs10743980 were associated with a decreased risk of bladder cancer in the recessive model in the initial analysis (OR 0.76, 95% CI 0.58-0.99, p=0.039). This was validated using the bladder genome-wide association study chip (OR 0.51, 95% CI 0.27-1.00, p=0.049 and for combined analysis p=0.007). Together these findings implicate variants in the Wnt/β-catenin stem cell pathway as having a role in bladder cancer etiology. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. CD24 negative lung cancer cells, possessing partial cancer stem cell properties, cannot be considered as cancer stem cells.

    Science.gov (United States)

    Xu, Haineng; Mu, Jiasheng; Xiao, Jing; Wu, Xiangsong; Li, Maolan; Liu, Tianrun; Liu, Xinyuan

    2016-01-01

    Cancer stem cells (CSCs) play vital role in lung cancer progression, resistance, metastasis and relapse. Identifying lung CSCs makers for lung CSCs targeting researches are critical for lung cancer therapy. In this study, utilizing previous identified lung CSCs as model, we compared the expression of CD24, CD133 and CD44 between CSCs and non-stem cancer cells. Increased ratio of CD24- cells were found in CSCs. CD24- cells were then sorted by flow cytometry and their proliferative ability, chemo-resistance property and in vivo tumor formation abilities were detected. A549 CD24- cells formed smaller colonies, slower proliferated in comparison to A549 CD24+ cells. Besides, A549 CD24- exhibited stronger resistance to chemotherapy drug. However, A549 CD24- didn't exert any stronger tumor formation ability in vivo, which is the gold standard of CSCs. These results showed that CD24- A549 cells showed some properties of CSCs but not actually CSCs. This study provides evidence that CD24 cannot be considered as lung CSCs marker.

  5. Single nucleotide polymorphisms as susceptibility, prognostic, and therapeutic markers of nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zienolddiny S

    2011-12-01

    Full Text Available Shanbeh Zienolddiny, Vidar SkaugSection for Toxicology and Biological Work Environment, National Institute of Occupational Health, Oslo, NorwayAbstract: Lung cancer is a major public health problem throughout the world. Among the most frequent cancer types (prostate, breast, colorectal, stomach, lung, lung cancer is the leading cause of cancer-related deaths worldwide. Among the two major subtypes of small cell lung cancer and nonsmall cell lung cancer (NSCLC, 85% of tumors belong to the NSCLC histological types. Small cell lung cancer is associated with the shortest survival time. Although tobacco smoking has been recognized as the major risk factor for lung cancer, there is a great interindividual and interethnic difference in risk of developing lung cancer given exposure to similar environmental and lifestyle factors. This may indicate that in addition to chemical and environmental factors, genetic variations in the genome may contribute to risk modification. A common type of genetic variation in the genome, known as single nucleotide polymorphism, has been found to be associated with susceptibility to lung cancer. Interestingly, many of these polymorphisms are found in the genes that regulate major pathways of carcinogen metabolism (cytochrome P450 genes, detoxification (glutathione S-transferases, adduct removal (DNA repair genes, cell growth/apoptosis (TP53/MDM2, the immune system (cytokines/chemokines, and membrane receptors (nicotinic acetylcholine and dopaminergic receptors. Some of these polymorphisms have been shown to alter the level of mRNA, and protein structure and function. In addition to being susceptibility markers, several of these polymorphisms are emerging to be important for response to chemotherapy/radiotherapy and survival of patients. Therefore, it is hypothesized that single nucleotide polymorphisms will be valuable genetic markers in individual-based prognosis and therapy in future. Here we will review some of the most

  6. Mechanisms of therapeutic resistance in cancer (stem cells with emphasis on thyroid cancer cells.

    Directory of Open Access Journals (Sweden)

    Sabine eHombach-Klonisch

    2014-03-01

    Full Text Available Tissue invasion, metastasis and therapeutic resistance to anti-cancer treatments are common and main causes of death in cancer patients. Tumor cells mount complex and still poorly understood molecular defense mechanisms to counteract and evade oxygen deprivation, nutritional restrictions as well as radio- and chemotherapeutic treatment regimens aimed at destabilizing their genomes and important cellular processes. In thyroid cancer, as in other tumors, such defense strategies include the reactivation in cancer cells of early developmental programs normally active exclusively in stem cells, the stimulation of cancer stem-like cells resident within the tumor tissue and the recruitment of bone marrow-derived progenitors into the tumor (Thomas et al., 2008;Klonisch et al., 2009;Derwahl, 2011. Metastasis and therapeutic resistance in cancer (stem cells involves the epithelial-to-mesenchymal transition- (EMT- mediated enhancement in cellular plasticity, which includes coordinated dynamic biochemical and nuclear changes (Ahmed et al., 2010. The purpose of the present review is to provide an overview of the role of DNA repair mechanisms contributing to therapeutic resistance in thyroid cancer and highlight the emerging roles of autophagy and damage associated molecular pattern (DAMP responses in EMT and chemoresistance in tumor cells. Finally, we use the stem cell factor and nucleoprotein High Mobility Group A2 (HMGA2 as an example to demonstrate how factors intended to protect stem cells are wielded by cancer (stem cells to gain increased transformative cell plasticity which enhances metastasis, therapeutic resistance and cell survival. Wherever possible, we have included information on these cellular processes and associated factors as they relate to thyroid cancer cells.

  7. [Sea urchin embryo, DNA-damaged cell cycle checkpoint and the mechanisms initiating cancer development].

    Science.gov (United States)

    Bellé, Robert; Le Bouffant, Ronan; Morales, Julia; Cosson, Bertrand; Cormier, Patrick; Mulner-Lorillon, Odile

    2007-01-01

    Cell division is an essential process for heredity, maintenance and evolution of the whole living kingdom. Sea urchin early development represents an excellent experimental model for the analysis of cell cycle checkpoint mechanisms since embryonic cells contain a functional DNA-damage checkpoint and since the whole sea urchin genome is sequenced. The DNA-damaged checkpoint is responsible for an arrest in the cell cycle when DNA is damaged or incorrectly replicated, for activation of the DNA repair mechanism, and for commitment to cell death by apoptosis in the case of failure to repair. New insights in cancer biology lead to two fundamental concepts about the very first origin of cancerogenesis. Cancers result from dysfunction of DNA-damaged checkpoints and cancers appear as a result of normal stem cell (NCS) transformation into a cancer stem cell (CSC). The second aspect suggests a new definition of "cancer", since CSC can be detected well before any clinical evidence. Since early development starts from the zygote, which is a primary stem cell, sea urchin early development allows analysis of the early steps of the cancerization process. Although sea urchins do not develop cancers, the model is alternative and complementary to stem cells which are not easy to isolate, do not divide in a short time and do not divide synchronously. In the field of toxicology and incidence on human health, the sea urchin experimental model allows assessment of cancer risk from single or combined molecules long before any epidemiologic evidence is available. Sea urchin embryos were used to test the worldwide used pesticide Roundup that contains glyphosate as the active herbicide agent; it was shown to activate the DNA-damage checkpoint of the first cell cycle of development. The model therefore allows considerable increase in risk evaluation of new products in the field of cancer and offers a tool for the discovery of molecular markers for early diagnostic in cancer biology

  8. Sugars, sucrose and colorectal cancer risk: the Fukuoka colorectal cancer study.

    Science.gov (United States)

    Wang, Zhenjie; Uchida, Kazuhiro; Ohnaka, Keizo; Morita, Makiko; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji

    2014-05-01

    A diet high in sugars may promote colorectal carcinogenesis, but it remains uncertain whether high intake of sugars or sucrose confers increased risk of colorectal cancer. The authors investigated the associations of sugars and sucrose intake with colorectal cancer risk in a community-based case-control study in Japan. The study subjects comprised 816 incident cases of colorectal cancer and 815 community controls. Consumption frequencies and portion sizes of 148 food and beverage items were ascertained by a computer-assisted interview. The authors used the consumption of 29 food items to estimate sugars and sucrose intake. The odds ratios of colorectal cancer risk according to intake categories were obtained using a logistic regression model with adjustment for potential confounding variables. Overall, intakes of sugars and sucrose were not related to colorectal cancer risk either in men or women. The association between sugars intake and colorectal cancer risk differed by smoking status and alcohol use in men, but not in women. In men, sugars intake tended to be associated with colorectal cancer risk inversely among never-smokers and positively among male ever-smokers (interaction p=0.01). Sugars intake was associated with an increased risk among men with no alcohol consumption, but was unrelated to the risk among male alcohol drinkers (interaction p=0.02). Body mass index did not modify the association with sugars intake in either men or women. Sugars intake was associated with increased risk of colorectal cancer among smokers and non-alcohol drinkers in men selectively.

  9. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tarek H. Mouhieddine

    2015-11-01

    Full Text Available Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma and SHSY-5Y (neuroblastoma cell lines.Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence.

  10. Prostate Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  11. Liver Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  12. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  13. Esophageal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  14. Bladder Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  15. Lung Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  16. Breast Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  17. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  18. Ovarian Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  19. Cervical Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  20. Testicular Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  1. Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal Cancers Undergo Asymmetric Cell Division

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Garfield, Susan H.; Thorgeirsson, Snorri S.; Avital, Itzhak

    2012-01-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  2. Awareness of risk factors for cancer

    DEFF Research Database (Denmark)

    Lagerlund, Magdalena; Hvidberg, Line; Hajdarevic, Senada

    2015-01-01

    Background: Sweden and Denmark are neighbouring countries with similarities in culture, healthcare, and economics, yet notable differences in cancer statistics. A crucial component of primary prevention is high awareness of risk factors in the general public. We aimed to determine and compare...... awareness of risk factors for cancer between a Danish and a Swedish population sample, and to examine whether there are differences in awareness across age groups. Methods: Data derive from Module 2 of the International Cancer Benchmarking Partnership. Telephone interviews were conducted with 3000 adults...... in Denmark and 3070 in Sweden using the Awareness and Beliefs about Cancer measure. Data reported here relate to awareness of 13 prompted risk factors for cancer. Prevalence ratios with 95 % confidence intervals were calculated to examine associations between country, age, and awareness of risk factors...

  3. Risk factors for cancer

    International Nuclear Information System (INIS)

    Lyman, G.H.

    1992-01-01

    It is no longer reasonable to divide cancers into those that are genetic in origin and those that are environmental in origin. With rare exception, carcinogenesis involves environmental factors that directly or indirectly exert a change in the cell's genome. Virtually all causes of cancer are multifactorial, sometimes involving an inherited predisposition to the carcinogenic effects of environmental factors, which include chemicals, ionizing radiation, and oncogenic virus. Carcinogenesis is a multistep process including induction, promotion, and progression. Initiation requires an irreversible change in the cellular genome, whereas promotion is commonly associated with prolonged and reversible exposure. Tumor progression results in genotypic and phenotypic changes associated with tumor growth, invasion, and metastasis. Most information on human cancer risk is based on epidemiologic studies involving both exposed and unexposed individuals. The quality of such studies depends on their ability to assess the strength of any association of exposure and disease and careful attention to any potential bias. Few cancers are inherited in a Mendelian fashion. Several preneoplastic conditions, however, are clearly inherited and several malignancies demonstrate weak familial patterns. Environmental factors may exert their effect on DNA in a random fashion, but certain consistent changes, including specific translocations of genetic information, are often found. Currently, there is great interest in the close proximity of certain oncogenes governing growth control to the consistent chromosomal changes observed. Such changes may represent a final common pathway of action for environmental carcinogens. Sufficient laboratory and epidemiologic evidence exists to establish a causal association of several chemical agents with cancer

  4. Radical prostatectomy for high-risk prostate cancer.

    Science.gov (United States)

    Yossepowitch, Ofer; Eastham, James A

    2008-06-01

    Consensus recommendations for the identification and treatment of men whose apparent organ confined prostate cancer has high risk features are lacking. Despite ongoing refinements in surgical technique and improvements in morbidity and functional outcomes, the tradition of steering high-risk patients away from radical prostatectomy (RP) remains steadfast. We performed a medical literature search in English using MEDLINE/PubMed that addressed high risk prostate cancer. We analyzed the literature with respect to the historical evolution of this concept, current risk stratification schemes and treatment guidelines and related short and long term outcomes following RP. Contemporary evidence suggest that patients classified with high-risk prostate cancer by commonly used definitions do not have a uniformly poor prognosis after RP. Many cancers categorized clinically as high risk are actually pathologically confined to the prostate, and most men with such cancers who undergo RP are alive and free of additional therapy long after surgery. RP in the high-risk setting appears to be associated with a similar morbidity as in lower-risk patients. Men with clinically localized high-risk prostate cancer should not be categorically disqualified from local definitive therapy with RP. With careful attention to surgical technique, cancer control rates should improve further, and adverse effects on quality of life after RP should continue to decrease.

  5. Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer.

    Science.gov (United States)

    Nayan, Madhur; Jewett, Michael A S; Hosni, Ali; Anson-Cartwright, Lynn; Bedard, Philippe L; Moore, Malcolm; Hansen, Aaron R; Chung, Peter; Warde, Padraig; Sweet, Joan; O'Malley, Martin; Atenafu, Eshetu G; Hamilton, Robert J

    2017-01-01

    Patients on surveillance for clinical stage I (CSI) testicular cancer are counseled regarding their baseline risk of relapse. The conditional risk of relapse (cRR), which provides prognostic information on patients who have survived for a period of time without relapse, have not been determined for CSI testicular cancer. To determine cRR in CSI testicular cancer. We reviewed 1239 patients with CSI testicular cancer managed with surveillance at a tertiary academic centre between 1980 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: cRR estimates were calculated using the Kaplan-Meier method. We stratified patients according to validated risk factors for relapse. We used linear regression to determine cRR trends over time. At orchiectomy, the risk of relapse within 5 yr was 42.4%, 17.3%, 20.3%, and 12.2% among patients with high-risk nonseminomatous germ cell tumor (NSGCT), low-risk NSGCT, seminoma with tumor size ≥3cm, and seminoma with tumor size testicular cancer is very low. Consideration should be given to adapting surveillance protocols to individualized risk of relapse based on cRR as opposed to static protocols based on baseline factors. This strategy could reduce the intensity of follow-up for the majority of patients. Our study is the first to provide data on the future risk of relapse during surveillance for clinical stage I testicular cancer, given a patient has been without relapse for a specified period of time. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  6. Risk assessment for cancer induction after low- and high-LET therapeutic irradiation

    International Nuclear Information System (INIS)

    Engels, H.; Menzel, H.G.; Pihet, P.; Wambersie, A.

    1999-01-01

    The risk of induction of a second primary cancer after a therapeutic irradiation with conventional photon beams is well recognized and documented. However, in general, it is totally overwhelmed by the benefit of the treatment. The same is true to a large extent for the combinations of radiation and drug therapy. After fast neutron therapy, the risk of induction of a second cancer is greater than after photon therapy. Neutron RBE increases with decreasing dose and there is a wide evidence that neutron RBE is greater for cancer induction (and for other late effects relevant in radiation protection) than for cell killing. Animal data on RBE for tumor induction are reviewed, as well as other biological effects such as life shortening, malignant cell transformation in vitro, chromosome aberrations, genetic effects. These effects can be related, directly or indirectly, to cancer induction to the extent that they express a 'genomic' lesions. Almost no reliable human epidemiological data are available so far. For fission neutrons a RBE for cancer induction of about 20 relative to photons seems to be a reasonable assumption. For fast neutrons, due to the difference in energy spectrum, a RBE of 10 can be assumed. After proton beam therapy (low-LET radiation), the risk of secondary cancer induction, relative to photons, can be divided by a factor of 3, due to the reduction of integral dose (as an average). The RBE of heavy-ions for cancer induction can be assumed to be similar to fission neutrons, i.e. about 20 relative to photons. However, after heavy-ion beam therapy, the risk should be divided by 3, as after proton therapy, due to the excellent physical selectivity of the irradiation. Therefore, a risk 5 to 10 times higher than photons could be assumed. This range is probably a pessimistic estimate for carbon ions since most of the normal tissues, at the level of the initial plateau, are irradiated with low-LET radiation. (orig.)

  7. Increased cancer risk in patients with periodontitis.

    Science.gov (United States)

    Dizdar, Omer; Hayran, Mutlu; Guven, Deniz Can; Yılmaz, Tolga Birtan; Taheri, Sahand; Akman, Abdullah C; Bilgin, Emre; Hüseyin, Beril; Berker, Ezel

    2017-12-01

    Previous studies have noted a possible association between periodontal diseases and the risk of various cancers. We assessed cancer risk in a cohort of patients with moderate to severe periodontitis. Patients diagnosed with moderate to severe periodontitis by a periodontist between 2001 and 2010 were identified from the hospital registry. Patients younger than 35 years of age or with a prior cancer diagnosis were excluded. The age- and gender-standardized incidence rates (SIR) were calculated by dividing the number of observed cases by the number of expected cases from Turkish National Cancer Registry 2013 data. A total of 280 patients were included (median age 49.6, 54% female). Median follow-up was 12 years. Twenty-five new cancer cases were observed. Patients with periodontitis had 77% increased risk of cancer (SIR 1.77, 95% CI 1.17-2.58, p = .004). Women with periodontitis had significantly higher risk of breast cancer (SIR 2.40, 95% CI 0.88-5.33) and men with periodontitis had significantly higher risk of prostate cancer (SIR 3.75, 95% CI 0.95-10.21) and hematological cancers (SIR 6.97, 95% CI 1.77-18.98). Although showing a causal association necessitates further investigation, our results support the idea that periodontitis might be associated with increased cancer risk, particularly with hematological, breast and prostate cancers.

  8. Northeast Regional Cancer Institute's Cancer Surveillance and Risk Factor Program

    Energy Technology Data Exchange (ETDEWEB)

    Lesko, Samuel M.

    2007-07-31

    OBJECTIVES The Northeast Regional Cancer Institute is conducting a program of ongoing epidemiologic research to address cancer disparities in northeast Pennsylvania. Of particular concern are disparities in the incidence of, stage at diagnosis, and mortality from colorectal cancer. In northeast Pennsylvania, age-adjusted incidence and mortality rates for colorectal cancer are higher, and a significantly smaller proportion of new colorectal cancer cases are diagnosed with local stage disease than is observed in comparable national data. Further, estimates of the prevalence of colorectal cancer screening in northeast Pennsylvania are lower than the US average. The Northeast Regional Cancer Institute’s research program supports surveillance of common cancers, investigations of cancer risk factors and screening behaviors, and the development of resources to further cancer research in this community. This project has the following specific objectives: I. To conduct cancer surveillance in northeast Pennsylvania. a. To monitor incidence and mortality for all common cancers, and colorectal cancer, in particular, and b. To document changes in the stage at diagnosis of colorectal cancer in this high-risk, underserved community. II. To conduct a population-based study of cancer risk factors and screening behavior in a six county region of northeast Pennsylvania. a. To monitor and document changes in colorectal cancer screening rates, and b. To document the prevalence of cancer risk factors (especially factors that increase the risk of colorectal cancer) and to identify those risk factors that are unusually common in this community. APPROACH Cancer surveillance was conducted using data from the Northeast Regional Cancer Institute’s population-based Regional Cancer Registry, the Pennsylvania Cancer Registry, and NCI’s SEER program. For common cancers, incidence and mortality were examined by county within the region and compared to data for similar populations in the US

  9. Local advanced transitional cell cancer and squamous cell cancer of ...

    African Journals Online (AJOL)

    Case report: A 51-year-old man presented with a locally advanced squamous cell cancer of the periurethral tissues as well as an underlying isolated transitional cell cancer of the urethra. Chemotherapy with Gemcitabin and Cisplatinum together with local radiation to the pelvis and the perineum was given. There was ...

  10. Therapy of solid cancers using T cells and running shoes

    DEFF Research Database (Denmark)

    Straten, Per Thor

    2017-01-01

    of tumor specific T cells at the tumor site, and underscores the need to define ways as how to increase immune cell infiltration to the tumor site. Regular exercise reduces the risk of cancer and disease recurrence, by largely unknown mechanisms. We recently demonstrated that voluntary wheel running showed...

  11. Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes.

    Science.gov (United States)

    Allison, Katrina E; Coomber, Brenda L; Bridle, Byram W

    2017-10-01

    Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and up-regulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system. Immune checkpoint blockade provides an example of how metabolism can be differentially impacted to impair cancer cells but support T cells. Implications for research with metabolic inhibitors are discussed. © 2017 John Wiley & Sons Ltd.

  12. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua, E-mail: wlhwq@yahoo.com

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  13. The diagnostic impact of testicular biopsies for intratubular germ cell neoplasia in cryptorchid boys and the subsequent risk of testicular cancer in men with prepubertal surgery for syndromic or non-syndromic cryptorchidism.

    Science.gov (United States)

    Osterballe, Lene; Clasen-Linde, Erik; Cortes, Dina; Engholm, Gerda; Hertzum-Larsen, Rasmus; Reinhardt, Susanne; Thorup, Jorgen

    2017-04-01

    Cryptorchidism is a risk factor for testicular cancer in adult life. It remains unclear how prepubertal surgery for cryptorchidism impacts later development of adult testicular cancer. The aim of study was to investigate tools to identify the cryptorchid boys who later develop testicular cancer. The study cohort consisted of 1403 men operated prepubertally/pubertally for undescended testis between 1971 and 2003. At surgery testicular biopsies were taken from the cryptorchid testes. The boys were followed for occurrence of testicular cancer. The testicular cancer risk was compared to the risk in the Danish Population. Testicular biopsies from the boys who developed testicular cancer during follow-up underwent histological examination with specific diagnostic immunohistochemical markers for germ cell neoplasia. The cohort was followed for 33,627 person years at risk. We identified 16 cases with testicular cancer in adulthood. The standardized incidence ratio was 2.66 (95% CI: 1.52-4.32). At time of primary surgery in prepubertal/pubertal age Intratubular Germ Cell Neoplasia (ITGCN) was diagnosed in 5 cases and the boys were unilaterally orchiectomized. At follow-up new immunohistochemical staining indicated ITGCN in two of the 16 cancer cases at reevaluation of the original biopsies from time of prepubertal/pubertal surgery. One had syndromic cryptorchid and developed seminoma, and another showed nonsyndromic cryptorchidism and developed embryonic teratocarcinoma. Totally, ITGCN was diagnosed in 0.5% (7/1403) of prepubertal cryptorchid boys, whereof 57% (4/7) in syndromic-cryptorchidism. ITGCN is predominantly observed prepubertally in boys with syndromic-cryptorchidism. In nonsyndromic cryptorchidism testicular cancer develops postpubertally, generally not based on dormant germ cells of ITGCN caused by an early fetal maldevelopment. LEVEL I. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. HIV Infection and Cancer Risk

    Science.gov (United States)

    ... same age ( 1 ). The general term for these cancers is "HIV-associated cancers." Three of these cancers are known as " acquired ... also have an increased cumulative risk of developing HIV-associated cancers. What can people infected with HIV do to ...

  15. Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

    Science.gov (United States)

    Johnson, Kevin C; Houseman, E Andres; King, Jessica E; Christensen, Brock C

    2017-07-10

    The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and family history of disease, with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 cytosine-guanine dinucleotide (CpG) sites that demonstrated significant associations (Q value breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations, using normal breast tissue samples (n = 18) and samples of normal tissue adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and invasive breast tumors (n = 731, P = 1.1E-13). DNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer, suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.

  16. Functional study of risk loci of stem cell-associated gene lin-28B and associations with disease survival outcomes in epithelial ovarian cancer.

    Science.gov (United States)

    Lu, Lingeng; Katsaros, Dionyssios; Mayne, Susan T; Risch, Harvey A; Benedetto, Chiara; Canuto, Emilie Marion; Yu, Herbert

    2012-11-01

    Several single-nucleotide polymorphisms (SNPs) of the stem cell-associated gene lin-28B have been identified in association with ovarian cancer and ovarian cancer-related risk factors. However, whether these SNPs are functional or might be potential biomarkers for ovarian cancer prognosis remains unknown. The purposes of this study were to investigate the functional relevance of the identified lin-28B SNPs, as well as the associations of genotype and phenotype with epithelial ovarian cancer (EOC) survival. We analyzed five SNPs and mRNA levels of lin-28B in 211 primary EOC tissues using Taqman(®) SNP genotyping assays and SYBR green-based real-time PCR, respectively. The RNA secondary structures at the region of a genome-wide association-identified intronic rs314276 were analyzed theoretically with mfold and experimentally with circular dichroism spectroscopy. We found that rs314276 was a cis-acting expression quantitative trait locus (eQTL) in both additive and dominant models, while rs7759938 and rs314277 were significant or of borderline significance in dominant models only. The rs314276 variant significantly affects RNA secondary structure. No SNPs alone were associated with patient survival. However, we found that among patients initially responding to chemotherapy, those with higher lin-28B expression had higher mortality risk (hazard ratio =3.27, 95% confidence interval: 1.63-6.56) and relapse risk (hazard ratio = 2.53, 95% confidence interval: 1.41-4.54) than those with lower expression, and these associations remained in multivariate analyses. These results suggest that rs314276 alters RNA secondary structure and thereby influences gene expression, and that lin-28B is a cancer stem cell-associated marker, which may be a pharmaceutical target in the management of EOC.

  17. Identifying colon cancer risk modules with better classification performance based on human signaling network.

    Science.gov (United States)

    Qu, Xiaoli; Xie, Ruiqiang; Chen, Lina; Feng, Chenchen; Zhou, Yanyan; Li, Wan; Huang, Hao; Jia, Xu; Lv, Junjie; He, Yuehan; Du, Youwen; Li, Weiguo; Shi, Yuchen; He, Weiming

    2014-10-01

    Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer. Copyright © 2013. Published by Elsevier Inc.

  18. Cancer stem cells in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Trapasso S

    2012-11-01

    Full Text Available Eugenia Allegra, Serena TrapassoOtolaryngology – Head and Neck Surgery, University Magna Graecia of Catanzaro, Catanzaro, ItalyAbstract: Cancer stem cells (CSCs, also called "cells that start the tumor," represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal, giving rise both to other tumor stem cells and most advanced cells in the line of differentiation (asymmetric division. A final characteristic is tumorigenicity, a fundamental property, which outlines the tumor stem cell as the only cell able to initiate the formation of a tumor when implanted in immune-deficient mice. The hypothesis of a hierarchical organization of tumor cells dates back more than 40 years, but only in 1997, thanks to the work of John Dick and Dominique Bonnet, was there the formal proof of such an organization in acute myeloid leukemia. Following this, many other research groups were able to isolate CSCs, by appropriate selection markers, in various malignancies, such as breast, brain, colon, pancreas, and liver cancers and in melanoma. To date, however, it is not possible to isolate stem cells from all types of neoplasia, particularly in solid tumors. From a therapeutic point of view, the concept of tumor stem cells implies a complete revision of conventional antineoplastic treatment. Conventional cytotoxic agents are designed to target actively proliferating cells. In the majority of cases, this is not sufficient to eliminate the CSCs, which thanks to their reduced proliferative activity and/or the presence of proteins capable of extruding chemotherapeutics from the cell are not targeted. Therefore, the theory of cancer stem cells can pose new paradigms in terms of cancer treatment. Potential approaches, even in the very early experimental stages, relate to the selective inhibition of pathways connected with self-renewal, or more specifically based on

  19. Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer

    International Nuclear Information System (INIS)

    Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis F; Romero-Ramos, Jose E; Olimon-Andalon, Vicente; Hernandez-Flores, Georgina; Lerma-Diaz, Jose M; Ortiz-Lazareno, Pablo C; Morgan-Villela, Gilberto; Toro-Arreola, Susana del; Bravo-Cuellar, Alejandro

    2008-01-01

    Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95) in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma). The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L) were measured by ELISA kits. We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of the apoptotic rate induced by serum in Jurkat cells and the

  20. Risk of subsequent gastrointestinal cancer among childhood cancer survivors : A systematic review

    NARCIS (Netherlands)

    Teepen, Jop C.; de Vroom, Suzanne L.; van Leeuwen, Flora E.; Tissing, Wim J.; Kremer, Leontien C.; Ronckers, Cecile M.

    Background: Childhood cancer survivors (CCS) are at increased risk of developing subsequent malignant neoplasms, including gastrointestinal (GI) cancer. We performed a systematic review to summarize all available literature on the risk of, risk factors for, and outcome after subsequent GI cancer

  1. Association of eNOS and ACE gene polymorphisms and plasma nitric oxide with risk of non-small cell lung cancer in South India.

    Science.gov (United States)

    Peddireddy, Vidyullatha; Badabagni, Siva Prasad; Gundimeda, Sandhya Devi; Mundluru, Hema Prasad

    2018-01-01

    The role of ACE and eNOS gene polymorphisms and their association with various cancers were reported. However, their role in the lung cancer is unclear. In this study, we analyzed eNOS and ACE gene polymorphisms and the risk of non-small cell lung cancer (NSCLC) in South Indian population. For the eNOS gene, the homozygous "AA" genotypic frequency was significantly associated with NSCLC with an overall risk of 3.6-fold (P = 0.006, odds ratio = 3.58, 95% confidence interval = 1.66, 7.723). The heterozygous "I/D" genotypic frequency of ACE gene was significantly higher in NSCLC patients when compared to the controls with a 2.29-fold risk for NSCLC. Multiple regression analyses indicated that gender, smoking status, and polymorphisms in eNOS and ACE genes as the strongest predicting factors for an increased susceptibility to NSCLC. We report for the first time that polymorphisms in the eNOS "A/A" (homozygous mutant) and ACE "I/D" genotypes might contribute to the increased risk of NSCLC in the South Indian population. © 2016 John Wiley & Sons Ltd.

  2. High body mass index and cancer risk

    DEFF Research Database (Denmark)

    Benn, Marianne; Tybjærg-Hansen, Anne; Smith, George Davey

    2016-01-01

    of follow-up (range 0-37), 8002 developed non-skin cancer, 3347 non-melanoma skin cancer, 1396 lung cancer, 637 other smoking related cancers, 1203 colon cancer, 159 kidney cancer, 1402 breast cancer, 1062 prostate cancer, and 2804 other cancers. Participants were genotyped for five genetic variants...... with a BMI ≥ 30 versus 18.5-24.9 kg/m(2). Corresponding risk of breast cancer was 20 % (0-44 %) higher in postmenopausal women. BMI was not associated with risk of colon, kidney, other smoking related cancers, prostate cancer, or other cancers. In genetic analyses, carrying 7-10 versus 0-4 BMI increasing......High body mass index (BMI) has been associated with increased risk of some cancer. Whether these reflect causal associations is unknown. We examined this issue. Using a Mendelian randomisation approach, we studied 108,812 individuals from the general population. During a median of 4.7 years...

  3. Epigallocatechin-3-gallate inhibits stem-like inflammatory breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Nora D Mineva

    Full Text Available Inflammatory Breast Cancer (IBC is a highly aggressive form of cancer characterized by high rates of proliferation, lymphangiogenesis and metastasis, and an overall poor survival. As regular green tea consumption has been associated with improved prognosis of breast cancer patients, including decreased risk of recurrence, here the effects of the green tea polyphenol epigallocatechin-3-gallate (EGCG were tested on two IBC lines: SUM-149 and SUM-190. EGCG decreased expression of genes that promote proliferation, migration, invasion, and survival. Consistently, growth, invasive properties, and survival of IBC cells were reduced by EGCG treatment. EGCG also reduced lymphangiogenesis-promoting genes, in particular VEGF-D. Conditioned media from EGCG-treated IBC cells displayed decreased VEGF-D secretion and reduced ability to promote lymphangiogenesis in vitro as measured by hTERT-HDLEC lymphatic endothelial cell migration and tube formation. Tumorsphere formation by SUM-149 cells was robustly inhibited by EGCG, suggesting effects on self-renewal ability. Stem-like SUM-149 cells with high aldehyde dehydrogenase (ALDH activity, previously implicated in poor patient prognosis, were isolated. EGCG treatment reduced growth and induced apoptosis of the stem-like SUM-149 cells in culture. In an orthotopic mouse model, EGCG decreased growth of pre-existing tumors derived from ALDH-positive stem-like SUM-149 cells and their expression of VEGF-D, which correlated with a significant decrease in peritumoral lymphatic vessel density. Thus, EGCG inhibits the overall aggressive IBC phenotype. Reduction of the stem-like cell compartment by EGCG may explain the decreased risk of breast cancer recurrence among green tea drinkers. Recent clinical trials demonstrate the efficacy of green tea polyphenol extracts in treatment of prostate cancer and lymphocytic leukemia with low toxicity. Given the poor prognosis of IBC patients, our findings suggest further exploration

  4. Nifedipine promotes the proliferation and migration of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Dong-Qing Guo

    Full Text Available Nifedipine is widely used as a calcium channel blocker (CCB to treat angina and hypertension,but it is controversial with respect the risk of stimulation of cancers. In this study, we demonstrated that nifedipine promoted the proliferation and migration of breast cancer cells both invivo and invitro. However, verapamil, another calcium channel blocker, didn't exert the similar effects. Nifedipine and high concentration KCl failed to alter the [Ca2+]i in MDA-MB-231 cells, suggesting that such nifedipine effect was not related with calcium channel. Moreover, nifedipine decreased miRNA-524-5p, resulting in the up-regulation of brain protein I3 (BRI3. Erk pathway was consequently activated and led to the proliferation and migration of breast cancer cells. Silencing BRI3 reversed the promoting effect of nifedipine on the breast cancer. In a summary, nifedipine stimulated the proliferation and migration of breast cancer cells via the axis of miRNA-524-5p-BRI3-Erk pathway independently of its calcium channel-blocking activity. Our findings highlight that nifedipine but not verapamil is conducive for breast cancer growth and metastasis, urging that the caution should be taken in clinic to prescribe nifedipine to women who suffering both hypertension and breast cancer, and hypertension with a tendency in breast cancers.

  5. HIV infection is associated with an increased risk for lung cancer, independent of smoking.

    Science.gov (United States)

    Kirk, Gregory D; Merlo, Christian; O' Driscoll, Peter; Mehta, Shruti H; Galai, Noya; Vlahov, David; Samet, Jonathan; Engels, Eric A

    2007-07-01

    Human immunodeficiency virus (HIV)-infected persons have an elevated risk for lung cancer, but whether the increase reflects solely their heavy tobacco use remains an open question. The Acquired Immunodeficiency Syndrome (AIDS) Link to the Intravenous Experience Study has prospectively observed a cohort of injection drug users in Baltimore, Maryland, since 1988, using biannual collection of clinical, laboratory, and behavioral data. Lung cancer deaths were identified through linkage with the National Death Index. Cox proportional hazards regression was used to examine the effect of HIV infection on lung cancer risk, controlling for smoking status, drug use, and clinical variables. Among 2086 AIDS Link to the Intravenous Experience Study participants observed for 19,835 person-years, 27 lung cancer deaths were identified; 14 of the deaths were among HIV-infected persons. All but 1 (96%) of the patients with lung cancer were smokers, smoking a mean of 1.2 packs per day. Lung cancer mortality increased during the highly active antiretroviral therapy era, compared with the pre-highly active antiretroviral therapy period (mortality rate ratio, 4.7; 95% confidence interval, 1.7-16). After adjusting for age, sex, smoking status, and calendar period, HIV infection was associated with increased lung cancer risk (hazard ratio, 3.6; 95% confidence interval, 1.6-7.9). Preexisting lung disease, particularly noninfectious diseases and asthma, displayed trends for increased lung cancer risk. Illicit drug use was not associated with increased lung cancer risk. Among HIV-infected persons, smoking remained the major risk factor; CD4 cell count and HIV load were not strongly associated with increased lung cancer risk, and trends for increased risk with use of highly active antiretroviral therapy were not significant. HIV infection is associated with significantly increased risk for developing lung cancer, independent of smoking status.

  6. Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Eley, John G., E-mail: jeley@som.umaryland.edu [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland (United States); Friedrich, Thomas [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Homann, Kenneth L.; Howell, Rebecca M. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Scholz, Michael; Durante, Marco [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Newhauser, Wayne D. [Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, Louisiana (United States); Mary Bird Perkins Cancer Center, Baton Rouge, Louisiana (United States)

    2016-05-01

    Purpose: This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients. Methods and Materials: We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breast by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model. Results: For our reference calculation, we found the predicted risk of breast cancer incidence for carbon-ion plans-to-proton plan ratio, , to be 0.75 ± 0.07 but not significantly smaller than 1 (P=.180). Conclusions: Our findings suggest that second cancer risks are, on average, comparable between proton therapy and carbon-ion therapy.

  7. Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?

    International Nuclear Information System (INIS)

    Chiodi, Ilaria; Belgiovine, Cristina; Donà, Francesca; Scovassi, A. Ivana; Mondello, Chiara

    2011-01-01

    Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs

  8. Colorectal cancer stem cells.

    Science.gov (United States)

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  9. Coffee and cancer risk: a summary overview.

    Science.gov (United States)

    Alicandro, Gianfranco; Tavani, Alessandra; La Vecchia, Carlo

    2017-09-01

    We reviewed available evidence on coffee drinking and the risk of all cancers and selected cancers updated to May 2016. Coffee consumption is not associated with overall cancer risk. A meta-analysis reported a pooled relative risk (RR) for an increment of 1 cup of coffee/day of 1.00 [95% confidence interval (CI): 0.99-1.01] for all cancers. Coffee drinking is associated with a reduced risk of liver cancer. A meta-analysis of cohort studies found an RR for an increment of consumption of 1 cup/day of 0.85 (95% CI: 0.81-0.90) for liver cancer and a favorable effect on liver enzymes and cirrhosis. Another meta-analysis showed an inverse relation for endometrial cancer risk, with an RR of 0.92 (95% CI: 0.88-0.96) for an increment of 1 cup/day. A possible decreased risk was found in some studies for oral/pharyngeal cancer and for advanced prostate cancer. Although data are mixed, overall, there seems to be some favorable effect of coffee drinking on colorectal cancer in case-control studies, in the absence of a consistent relation in cohort studies. For bladder cancer, the results are not consistent; however, any possible direct association is not dose and duration related, and might depend on a residual confounding effect of smoking. A few studies suggest an increased risk of childhood leukemia after maternal coffee drinking during pregnancy, but data are limited and inconsistent. Although the results of studies are mixed, the overall evidence suggests no association of coffee intake with cancers of the stomach, pancreas, lung, breast, ovary, and prostate overall. Data are limited, with RR close to unity for other neoplasms, including those of the esophagus, small intestine, gallbladder and biliary tract, skin, kidney, brain, thyroid, as well as for soft tissue sarcoma and lymphohematopoietic cancer.

  10. Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Ping Wang

    Full Text Available Lung cancer (LC with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC, large cell carcinoma (LCC, squamous cell carcinoma (SCC and adenocarcinoma (AC. We identified a small population of cells strongly positive for CD44 (CD44(high and a main population which was either weakly positive or negative for CD44 (CD44(low/-. Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44(highCD90(+ sub-population. Moreover, these CD44(highCD90(+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44(highCD90(+ population a good candidate for the lung CSCs. Both CD44(highCD90(+ and CD44(highCD90(- cells in the PLCCL derived from SCC formed spheroids, whereas the CD44(low/- cells were lacking this potential. These results indicate that CD44(highCD90(+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44(high sub-population.

  11. Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines

    Science.gov (United States)

    Suo, Zhenhe; Munthe, Else; Solberg, Steinar; Ma, Liwei; Wang, Mengyu; Westerdaal, Nomdo Anton Christiaan; Kvalheim, Gunnar; Gaudernack, Gustav

    2013-01-01

    Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44high) and a main population which was either weakly positive or negative for CD44 (CD44low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44highCD90+ sub-population. Moreover, these CD44highCD90+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44highCD90+ population a good candidate for the lung CSCs. Both CD44highCD90+ and CD44highCD90− cells in the PLCCL derived from SCC formed spheroids, whereas the CD44low/− cells were lacking this potential. These results indicate that CD44highCD90+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44high sub-population. PMID:23469181

  12. Height and Breast Cancer Risk

    DEFF Research Database (Denmark)

    Zhang, Ben; Shu, Xiao-Ou; Delahanty, Ryan J

    2015-01-01

    BACKGROUND: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. METHODS: We performed a meta......-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using...... a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control patients. RESULTS: The pooled relative risk of breast cancer was 1.17 (95% confidence...

  13. Estimated risk for secondary cancer in the contra-lateral breast following radiation therapy of breast cancer

    International Nuclear Information System (INIS)

    Johansen, Safora; Danielsen, Turi; Olsen, Dag Rune

    2008-01-01

    Purpose. To facilitate a discussion about the impact of dose heterogeneity on the risk for secondary contralateral breast (CB) cancer predicted with linear and non linear models associated with primary breast irradiation. Methods and materials. Dose volume statistics of the CB calculated for eight patients using a collapsed cone algorithm were used to predict the excess relative risk (ERR) for cancer induction in CB. Both linear and non-linear models were employed. A sensitivity analysis demonstrating the impact of different parameter values on calculated ERR for the eight patients was also included in this study. Results. A proportionality assumption was established to make the calculations with a linear and non-linear model comparable. ERR of secondary cancer predicted by the linear model varied considerably between the patients, while the predicted ERR for the same patients using the non-linear model showed very small variation. The predicted ERRs by the two models were indistinguishable for small doses, i.e. below ∼3 Gy. The sensitivity analysis showed that the quadratic component of the radiation-induction pre-malignant cell term is negligible for lower dose level. The ERR is highly sensitive to the value of agr1 and agr2. Conclusions. Optimization of breast cancer radiation therapy, where also the risk for radiation induced secondary malignancies in the contralateral breast is taken into account, requires robust and valid risk assessment. The linear dose-risk model does not account for the complexity in the mechanisms underlying the development of secondary malignancies following exposure to radiation; this is particularly important when estimating risk associated with highly heterogeneous dose distributions as is the case in the contralateral breast of women receiving breast cancer irradiation

  14. Genetic cancer risk assessment in practice

    International Nuclear Information System (INIS)

    Gruber, S.

    2004-01-01

    The advent of genetic testing has made a dramatic impact on the management of individuals with inherited susceptibility to cancer and their relatives. Genetic counsel ing, with or without testing, is warranted when clues to familial cancer are recognized. Today, genetic testing for classic cancer genetic syndromes is now the standard of care, and has been complemented by genetic testing for other situations commonly encountered in clinical practice. Genetic testing for colorectal cancer, breast cancer, kidney cancer, thyroid cancer, melanoma, and pancreatic cancer raise important issues about the parameters for testing. Genetic cancer risk assessment can lead to measurable reductions in morbidity and mortality through strategies that rely on surveillance, chemo prevention, and risk-reducing surgery

  15. Long-Term Survival and Risk of Second Cancers After Radiotherapy for Cervical Cancer

    International Nuclear Information System (INIS)

    Ohno, Tatsuya; Kato, Shingo; Sato, Shinichiro; Fukuhisa, Kenjiro; Nakano, Takashi; Tsujii, Hirohiko; Arai, Tatsuo

    2007-01-01

    Purpose: To evaluate the risk of second cancers after cervical cancer treated with radiotherapy for Asian populations. Methods and Materials: We reviewed 2,167 patients with cervical cancer undergoing radiotherapy between 1961 and 1986. Intracavitary brachytherapy was performed with high-dose rate source (82%) or low-dose rate source (12%). Relative risk (RR), absolute excess risk (AR), and cumulative risk of second cancer were calculated using the Japanese disease expectancy table. For 1,031 patients, the impact of smoking habit on the increasing risk of second cancer was also evaluated. Results: The total number of person-years of follow-up was 25,771, with 60 patients being lost to follow-up. Among the 2,167 patients, 1,063 (49%) survived more than 10 years. Second cancers were observed in 210 patients, representing a significant 1.2-fold risk (95% confidence interval [CI], 1.1-1.4) of developing second cancer compared with the general population, 1.6% excess risk per person per decade of follow-up, and elevating cumulative risk up to 23.8% (95% CI, 20.3-27.3) at 30 years after radiotherapy. The RR of second cancer was 1.6-fold for patients with the smoking habit and 1.4-fold for those without. Conclusions: Small but significant increased risk of second cancer was observed among Japanese women with cervical cancer mainly treated with high-dose rate brachytherapy. Considering the fact that about half of the patients survived more than 10 years, the benefit of radiotherapy outweighs the risk of developing second cancer

  16. Emotional, Biological, and Cognitive Impact of a Brief Expressive Writing Intervention for African American Women at Familial Breast Cancer Risk

    National Research Council Canada - National Science Library

    Valdimarsdottir, Heiddie; Bovbjerg, Dana

    2005-01-01

    Women at familial breast cancer risk have highly inflated perceptions of their risk of developing the disease, high levels of cancer specific distress, and lower levels of natural killer cell activity (NKCA...

  17. A regulatory variant in CYP2E1 affects the risk of lung squamous cell carcinoma.

    Science.gov (United States)

    Cao, Lei; Lin, Jia; He, Bing; Wang, Hongge; Rao, Juan; Liu, Yingwen; Zhang, Xuemei

    2014-01-01

    Cytochrome P450 2E1 (CYP2E1), an ethanol-inducible enzyme, has been shown to metabolically activate various carcinogens, which is critical for the development of cancers. It has been demonstrated that CYP2E1 polymorphisms alter the transcriptional activity. However, studies on the association between CYP2E1 -1239G>C polymorphism and non-small cell lung cancer have reported conflicting results. Thus, the gain of the present study was to investigate whether CYP2E1 -1239G>C polymorphism is associated with the development of non-small cell lung cancer in Chinese population. A case-control study was conducted in which CYP2E1 -1239G>C polymorphism was analyzed in 526 Chinese patients with non-small cell lung cancer and 526 age-matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism. Odds ratios were estimated by multivariate logistic regression. A meta-analysis was conducted to evaluate the association of CYP2E1 -1239G>C polymorphism with the risk of lung cancer in Chinese population by calculating pooled odds ratio (OR). For CYP2E1 -1239G>C polymorphism, -1239C allele carriers (OR = 0.67; 95% confidence interval (CI) = 0.51-0.87; P = 0.002) were associated with a decreased risk of non-small cell lung cancer when compared with -1239GG homozygotes. In the group analyses by pathological types, for lung squamous cell carcinoma and other types, the ORs of the C allele carriers were 0.60 (95% CI = 0.41-0.88; P = 0.009) and 0.54 (95% CI = 0.30-0.99; P = 0.045). In the group analysis of smoking status, the OR for the -1239C allele-containing genotype was higher than that for -1239GG genotype (OR = 0.57; 95% CI = 0.40-0.81; P = 0.002) among smokers, but not among nonsmokers. Moreover, when the risk associated with CYP2E1 polymorphism was further evaluated within strata of C polymorphism and the risk of non-small cell lung cancer. Meta-analysis data also showed that the carriers of CYP2E1 -1239C allele

  18. Accounting for individualized competing mortality risks in estimating postmenopausal breast cancer risk

    Science.gov (United States)

    Schonberg, Mara A.; Li, Vicky W.; Eliassen, A. Heather; Davis, Roger B.; LaCroix, Andrea Z.; McCarthy, Ellen P.; Rosner, Bernard A.; Chlebowski, Rowan T.; Hankinson, Susan E.; Marcantonio, Edward R.; Ngo, Long H.

    2016-01-01

    Purpose Accurate risk assessment is necessary for decision-making around breast cancer prevention. We aimed to develop a breast cancer prediction model for postmenopausal women that would take into account their individualized competing risk of non-breast cancer death. Methods We included 73,066 women who completed the 2004 Nurses’ Health Study (NHS) questionnaire (all ≥57 years) and followed participants until May 2014. We considered 17 breast cancer risk factors (health behaviors, demographics, family history, reproductive factors), 7 risk factors for non-breast cancer death (comorbidities, functional dependency), and mammography use. We used competing risk regression to identify factors independently associated with breast cancer. We validated the final model by examining calibration (expected-to-observed ratio of breast cancer incidence, E/O) and discrimination (c-statistic) using 74,887 subjects from the Women’s Health Initiative Extension Study (WHI-ES; all were ≥55 years and followed for 5 years). Results Within 5 years, 1.8% of NHS participants were diagnosed with breast cancer (vs. 2.0% in WHI-ES, p=0.02) and 6.6% experienced non-breast cancer death (vs. 5.2% in WHI-ES, prisk factors, 5 comorbidities, functional dependency, and mammography use. The model’s c-statistic was 0.61 (95% CI [0.60–0.63]) in NHS and 0.57 (0.55–0.58) in WHI-ES. On average our model under predicted breast cancer in WHI-ES (E/O 0.92 [0.88–0.97]). Conclusions We developed a novel prediction model that factors in postmenopausal women’s individualized competing risks of non-breast cancer death when estimating breast cancer risk. PMID:27770283

  19. Environmental risk factors for oesophageal cancer in Malawi: A case ...

    African Journals Online (AJOL)

    Methods A hospital-based case-control study of the association between environmental risk factors and oesophageal cancer was conducted at Kamuzu Central Hospital in Lilongwe, Malawi and Queen Elizabeth Central Hospital in Blantyre, Malawi. Ninety-six persons with squamous cell carcinoma and 180 controls were ...

  20. Stressful life events and cancer risk

    DEFF Research Database (Denmark)

    Bergelt, C; Prescott, E; Grønbaek, M

    2006-01-01

    In a prospective cohort study in Denmark of 8736 randomly selected people, no evidence was found among 1011 subjects who developed cancer that self-reported stressful major life events had increased their risk for cancer.......In a prospective cohort study in Denmark of 8736 randomly selected people, no evidence was found among 1011 subjects who developed cancer that self-reported stressful major life events had increased their risk for cancer....

  1. Night Shift Work and Risk of Breast Cancer.

    Science.gov (United States)

    Hansen, Johnni

    2017-09-01

    Night work is increasingly common and a necessity in certain sectors of the modern 24-h society. The embedded exposure to light-at-night, which suppresses the nocturnal hormone melatonin with oncostatic properties and circadian disruption, i.e., misalignment between internal and external night and between cells and organs, are suggested as main mechanisms involved in carcinogenesis. In 2007, the International Agency for Research on Cancer (IARC) classified shift work that involves circadian disruption as probably carcinogenic to humans based on limited evidence from eight epidemiologic studies on breast cancer, in addition to sufficient evidence from animal experiments. The aim of this review is a critical update of the IARC evaluation, including subsequent and the most recent epidemiologic evidence on breast cancer risk after night work. After 2007, in total nine new case-control studies, one case-cohort study, and eight cohort studies are published, which triples the number of studies. Further, two previous cohorts have been updated with extended follow-up. The assessment of night shift work is different in all of the 26 existing studies. There is some evidence that high number of consecutive night shifts has impact on the extent of circadian disruption, and thereby increased breast cancer risk, but this information is missing in almost all cohort studies. This in combination with short-term follow-up of aging cohorts may explain why some cohort studies may have null findings. The more recent case-control studies have contributed interesting results concerning breast cancer subtypes in relation to both menopausal status and different hormonal subtypes. The large differences in definitions of both exposure and outcome may contribute to the observed heterogeneity of results from studies of night work and breast cancer, which overall points in the direction of an increased breast cancer risk, in particular after over 20 years of night shifts. Overall, there is a

  2. Long-Term Lithium Use and Risk of Renal and Upper Urinary Tract Cancers

    DEFF Research Database (Denmark)

    Pottegård, Anton; Hallas, Jesper; Jensen, Boye L

    2015-01-01

    Lithium induces proliferation in the epithelium of renal collecting ducts. A recent small-scale cohort study reported a strong association between use of lithium and increased risk of renal neoplasia. We therefore conducted a large-scale pharmacoepidemiologic study of the association between long...... stratified by stage and subtype of upper urinary tract cancer revealed slight but nonsignificant increases in the ORs for localized disease (OR, 1.6; 95% CI, 0.8-3.0) and for renal pelvis/ureter cancers (OR, 1.7; 95% CI, 0.5-5.4). In conclusion, in our nationwide case-control study, use of lithium......-term use of lithium and risk of upper urinary tract cancer, including renal cell cancer and cancers of the renal pelvis or ureter. We identified all histologically verified upper urinary tract cancer cases in Denmark between 2000 and 2012 from the Danish Cancer Registry. A total of 6477 cases were matched...

  3. Risk factors for breast cancer in the breast cancer risk model study of Guam and Saipan.

    Science.gov (United States)

    Leon Guerrero, Rachael T; Novotny, Rachel; Wilkens, Lynne R; Chong, Marie; White, Kami K; Shvetsov, Yurii B; Buyum, Arielle; Badowski, Grazyna; Blas-Laguaña, Michelle

    2017-10-01

    Chamorro Pacific Islanders in the Mariana Islands have breast cancer incidence rates similar to, but mortality rates higher than, those of U.S. women. As breast cancer risk factors of women of the Mariana Islands may be unique because of ethnic and cultural differences, we studied established and suspected risk factors for breast cancer in this unstudied population. From 2010-2013, we conducted retrospective case-control study of female breast cancer (104 cases and 185 controls) among women in the Mariana Islands. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each of various lifestyle-related factors from logistic regression of breast cancer, in all women and in pre- and postmenopausal women separately. Tests for interaction of risk factors with ethnicity were based on the Wald statistics for cross-product terms. Of the medical and reproductive factors considered - age at menarche, breastfeeding, number of live births, age at first live birth, hormone use, and menopause - only age at first live birth was confirmed. Age at first live birth, among parous women, was higher among cases (mean 24.9 years) than controls (mean 23.2 years); with increased breast cancer risk (OR=2.53; 95% CI, 1.04-6.19 for age≥30y compared to risk and only in Filipino women. The association with many other established risk factors, such as BMI, hormone use and physical activity, were in the expected direction but were not significant. Associations for family history of breast cancer and alcohol intake were not evident CONCLUSIONS: The results provide a basis for cancer prevention guidance for women in the Mariana Islands. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  4. Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development.

    Science.gov (United States)

    Degnim, Amy C; Hoskin, Tanya L; Arshad, Muhammad; Frost, Marlene H; Winham, Stacey J; Brahmbhatt, Rushin A; Pena, Alvaro; Carter, Jodi M; Stallings-Mann, Melody L; Murphy, Linda M; Miller, Erin E; Denison, Lori A; Vachon, Celine M; Knutson, Keith L; Radisky, Derek C; Visscher, Daniel W

    2017-07-15

    Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD). Experimental Design: A breast tissue matched case-control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm 2 for CD4 + T cells, CD8 + T cells, CD20 + B cells, and CD68 + macrophages and quantification of positive pixel measure for CD11c (dendritic cells). Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8 + T cells, CD11c + dendritic cells, CD20 + B cells, and CD68 + macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20 + cell density ( P = 0.04). Nearly 42% of BBD cases had no CD20 + B cells in evaluated lobules compared with 28% of BBD controls ( P = 0.02). The absence of CD20 + cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4-23.1) for subsequent breast cancer risk. Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. Clin Cancer Res; 23(14); 3945-52. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Polyunsaturated fatty acids and prostate cancer risk

    DEFF Research Database (Denmark)

    Khankari, Nikhil K; Murff, Harvey J; Zeng, Chenjie

    2016-01-01

    BACKGROUND: Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations...... and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (ORLA=0.95, 95%CI=0.92, 0.98) and α-linolenic acids (ORALA=0.96, 95%CI=0.93, 0.98), among men ...-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men

  6. Stem cells and cancer: A review

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2016-05-01

    Full Text Available Stem cells are the small units of multicellular creature. Regeneration and self-renewal are the ability of the stem cells. Each tissue is having particular stem cells, specific to it. These normal stem cells are converted into cancer stem cells through mutations in it. Although the expression of oncogenes is enhanced a lot, the tumor-supressing gene is lessened. Cancer stem cells are isolated and visualized through different techniques like immunocytochemical staining, spectral karyotyping, immunohistochemistry, induction method and dissection measures, then are performed histological procedures which include fascination, immunohistochemistry, dispensation, in situ hybridization and also quantitative examination of tissue flow cytometric analysis. For the analysis of quantization, statistical tests are also performed as two-sample t-test, Chi-square test, SD and arithmetic mean. Tumor cells generate glioma spheres. These are used in cancer study. Axin 1 is the gene suppressing cancer. Its removal causes the generation of liver cancer. Curcumin is the most effective for suppressing cancer as it increases the normal stem cell function and decreases the cancer stem cell function. Brahma-related gene 1 is crucial for the safeguarding of the stem cell residents in tissue-specific comportment. Different types of cancers originate through genetic mutation, tissue disorganization and cell proliferation. Tumor configuration is produced by the alteration in original cell culture having stem cells and progenitor cell populations. The developmental facets about cancer cells and cancer stem cells as well as their personal natal functions sustain an intricate steadiness to settle on their personal donations to the efficacy or harmfulness of the biological organization.

  7. Prospectively-Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort

    Science.gov (United States)

    Pathak, Anand; Adams, Charleen D.; Loud, Jennifer T.; Nichols, Kathryn; Stewart, Douglas R.; Greene, Mark H.

    2015-01-01

    Background Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly-penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown. Methods We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat. Results Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR=11.9; 95% confidence interval [CI]=5.1–23.4; excess absolute risk=7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR=13.4; 95%CI=1.6–48.6). Conclusions Our data are the first indicating that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer. Impact Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies. PMID:26265202

  8. The progesterone receptor Val660→Leu polymorphism and breast cancer risk

    International Nuclear Information System (INIS)

    De Vivo, Immaculata; Hankinson, Susan E; Colditz, Graham A; Hunter, David J

    2004-01-01

    Recent evidence suggests a role for progesterone in breast cancer development and tumorigenesis. Progesterone exerts its effect on target cells by interacting with its receptor; thus, genetic variations, which might cause alterations in the biological function in the progesterone receptor (PGR), can potentially contribute to an individual's susceptibility to breast cancer. It has been reported that the PROGINS allele, which is in complete linkage disequilibrium with a missense substitution in exon 4 (G/T, valine→leucine, at codon 660), is associated with a decreased risk for breast cancer. Using a nested case-control study design within the Nurses' Health Study cohort, we genotyped 1252 cases and 1660 matched controls with the use of the Taqman assay. We did not observe any association of breast cancer risk with carrying the G/T (Val660→Leu) polymorphism (odds ratio 1.10, 95% confidence interval 0.93–1.30). In addition, we did not observe an interaction between this allele and menopausal status and family history of breast cancer as reported previously. Overall, our study does not support an association between the Val660→Leu PROGINS polymorphism and breast cancer risk

  9. Personal history of rosacea and risk of incident cancer among women in the US.

    Science.gov (United States)

    Li, W-Q; Zhang, M; Danby, F W; Han, J; Qureshi, A A

    2015-07-28

    Rosacea is an inflammatory skin disease. We examined the association between personal history of rosacea and risk of incident cancers. A total of 75 088 whites were included from the Nurses' Health Study II (1991-2011). Information on clinician-diagnosed rosacea and diagnosis year was collected in 2005. All cancers other than basal cell carcinoma (BCC) were confirmed. During 1 447 205 person-years, we identified 5194 cases with internal malignancies and 5788 with skin cancers. We did not observe significant associations between personal history of rosacea and internal malignancies, except for thyroid cancer (hazard ratio (HR)=1.59, 95% confidence interval (CI)=1.07-2.36). Among skin cancers, personal history of rosacea was associated with an elevated risk of BCC (HR=1.50, 95% CI=1.35-1.67). We suggest possible associations between personal history of rosacea and an increased risk of thyroid cancer and BCC. Further studies are warranted to replicate our findings and to explore the underlying mechanisms.

  10. Avoiding the ingestion of cytotoxic concentrations of ethanol may reduce the risk of cancer associated with alcohol consumption.

    Science.gov (United States)

    Guillén-Mancina, Emilio; Calderón-Montaño, José Manuel; López-Lázaro, Miguel

    2018-02-01

    Alcohol consumption is a known risk factor for cancer. Almost 6% of all cancers worldwide are attributable to alcohol use. Approximately half of them occur in tissues highly exposed to ethanol, such as the oral cavity, pharynx, upper larynx and esophagus. However, since ethanol is not mutagenic and the mutagenic metabolite of ethanol (acetaldehyde) is mainly produced in the liver, it is unclear why alcohol consumption preferentially exerts a local carcinogenic effect. Recent findings indicate that the risk of cancer in a tissue is strongly correlated with the number of stem cell divisions accumulated by the tissue; the accumulation of stem cell divisions leads to the accumulation of cancer-promoting errors such as mutations occurring during DNA replication. Since cell death activates the division of stem cells, we recently proposed that the possible cytotoxicity of ethanol on the cells lining the tissues in direct contact with alcoholic beverages could explain the local carcinogenic effect of alcohol. Here we report that short-term exposures (2-3 s) to ethanol concentrations between 10% and 15% start to cause a marked cytotoxic effect on human epithelial keratinocytes in a concentration-dependent manner. We propose that choosing alcoholic beverages containing non-cytotoxic concentrations of ethanol, or diluting ethanol to non-cytotoxic concentrations, may be a simple and effective way to reduce the risk of cancers of the oral cavity, pharynx, larynx and esophagus in alcohol users. This preventive strategy may also reduce the known synergistic effect of alcohol drinking and tobacco smoking on the risk of these cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Nutrients and Risk of Colon Cancer

    Directory of Open Access Journals (Sweden)

    Les Mery

    2010-02-01

    Full Text Available Dietary fats are thought to be important in the etiology of colon cancer. However, the evidence linking them is inconclusive. Studies on dietary protein, cholesterol and carbohydrate and the risk of colon cancer are also inconsistent. This study examined the association between dietary intake of protein, fats, cholesterol and carbohydrates, and the risk of colon cancer. Mailed questionnaires were completed by 1731 individuals with histologically confirmed cases of colon cancer and 3097 population controls between 1994 and 1997 in seven Canadian provinces. Measurements included socio-economic status, lifestyle habits and diet. A 69-item food frequency questionnaire was used to provide data on eating habits from two years before the study. Odds ratios (OR and 95% confidence intervals (CI were computed using unconditional logistic regression. The nutrients were categorized by quartiles based on the distributions among the controls. Intake of polyunsaturated fat, trans-fat and cholesterol were significantly associated with the risk of colon cancer; the ORs for the highest quartiles were 1.36 (95% CI, 1.02–1.80, 1.37 (95% CI, 1.10–1.71 and 1.42 (95% CI, 1.10–1.84, respectively. The association was stronger with proximal colon cancer (PCC. An increased risk was also observed with increasing intake of sucrose for both proximal and distal colon cancers; the ORs for the highest quartiles were 1.67 (95% CI, 1.22–2.29 for PCC and 1.58 (95% CI, 1.18–2.10 for distal colon cancer (DCC. An elevated risk of PCC was also found with increased lactose intake. Our findings provide evidence that a diet low in fat and sucrose could reduce the risk of various colon cancers.

  12. Nutrients and Risk of Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Jinfu, E-mail: Jinfu.hu@phac-aspc.gc.ca [Evidence and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, 785 Carling Avenue, AL: 6807B, Ottawa, Ontario K1A 0K9 (Canada); La Vecchia, Carlo [Istituto di Ricerche Farmacologiche “Mario Negri,” Via La Masa, 19-20156 Milan (Italy); Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Via Venezian, 1, 20133 Milan (Italy); Negri, Eva [Istituto di Ricerche Farmacologiche “Mario Negri,” Via La Masa, 19-20156 Milan (Italy); Mery, Les [Evidence and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, 785 Carling Avenue, AL: 6807B, Ottawa, Ontario K1A 0K9 (Canada)

    2010-02-10

    Dietary fats are thought to be important in the etiology of colon cancer. However, the evidence linking them is inconclusive. Studies on dietary protein, cholesterol and carbohydrate and the risk of colon cancer are also inconsistent. This study examined the association between dietary intake of protein, fats, cholesterol and carbohydrates, and the risk of colon cancer. Mailed questionnaires were completed by 1731 individuals with histologically confirmed cases of colon cancer and 3097 population controls between 1994 and 1997 in seven Canadian provinces. Measurements included socio-economic status, lifestyle habits and diet. A 69-item food frequency questionnaire was used to provide data on eating habits from two years before the study. Odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression. The nutrients were categorized by quartiles based on the distributions among the controls. Intake of polyunsaturated fat, trans-fat and cholesterol were significantly associated with the risk of colon cancer; the ORs for the highest quartiles were 1.36 (95% CI, 1.02–1.80), 1.37 (95% CI, 1.10–1.71) and 1.42 (95% CI, 1.10–1.84), respectively. The association was stronger with proximal colon cancer (PCC). An increased risk was also observed with increasing intake of sucrose for both proximal and distal colon cancers; the ORs for the highest quartiles were 1.67 (95% CI, 1.22–2.29) for PCC and 1.58 (95% CI, 1.18–2.10) for distal colon cancer (DCC). An elevated risk of PCC was also found with increased lactose intake. Our findings provide evidence that a diet low in fat and sucrose could reduce the risk of various colon cancers.

  13. Nutrients and Risk of Colon Cancer

    International Nuclear Information System (INIS)

    Hu, Jinfu; La Vecchia, Carlo; Negri, Eva; Mery, Les

    2010-01-01

    Dietary fats are thought to be important in the etiology of colon cancer. However, the evidence linking them is inconclusive. Studies on dietary protein, cholesterol and carbohydrate and the risk of colon cancer are also inconsistent. This study examined the association between dietary intake of protein, fats, cholesterol and carbohydrates, and the risk of colon cancer. Mailed questionnaires were completed by 1731 individuals with histologically confirmed cases of colon cancer and 3097 population controls between 1994 and 1997 in seven Canadian provinces. Measurements included socio-economic status, lifestyle habits and diet. A 69-item food frequency questionnaire was used to provide data on eating habits from two years before the study. Odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression. The nutrients were categorized by quartiles based on the distributions among the controls. Intake of polyunsaturated fat, trans-fat and cholesterol were significantly associated with the risk of colon cancer; the ORs for the highest quartiles were 1.36 (95% CI, 1.02–1.80), 1.37 (95% CI, 1.10–1.71) and 1.42 (95% CI, 1.10–1.84), respectively. The association was stronger with proximal colon cancer (PCC). An increased risk was also observed with increasing intake of sucrose for both proximal and distal colon cancers; the ORs for the highest quartiles were 1.67 (95% CI, 1.22–2.29) for PCC and 1.58 (95% CI, 1.18–2.10) for distal colon cancer (DCC). An elevated risk of PCC was also found with increased lactose intake. Our findings provide evidence that a diet low in fat and sucrose could reduce the risk of various colon cancers

  14. Height, selected genetic markers and prostate cancer risk

    DEFF Research Database (Denmark)

    Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia

    2017-01-01

    Background:Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer.Methods:We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases...... and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions.Results:The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm...... are at a 22% increased risk as compared to men with height prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer...

  15. Multifaceted Interpretation of Colon Cancer Stem Cells.

    Science.gov (United States)

    Hatano, Yuichiro; Fukuda, Shinya; Hisamatsu, Kenji; Hirata, Akihiro; Hara, Akira; Tomita, Hiroyuki

    2017-07-05

    Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but essential to cure the malignant foci completely. Herein, we review the recent evidence for intestinal stem cells and colon cancer stem cells, methods to detect the tumor-initiating cells, and clinical significance of cancer stem cell markers. We also describe the emerging problems of cancer stem cell theory, including bidirectional conversion and intertumoral heterogeneity of stem cell phenotype.

  16. Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

    DEFF Research Database (Denmark)

    Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan

    2010-01-01

    ,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region......According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C...

  17. Epigenetics in cancer stem cells.

    Science.gov (United States)

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  18. Squamous cell skin cancer

    Science.gov (United States)

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

  19. Colon Cancer Risk Assessment - Gauss Program

    Science.gov (United States)

    An executable file (in GAUSS) that projects absolute colon cancer risk (with confidence intervals) according to NCI’s Colorectal Cancer Risk Assessment Tool (CCRAT) algorithm. GAUSS is not needed to run the program.

  20. Diet and breast cancer: understanding risks and benefits.

    Science.gov (United States)

    Thomson, Cynthia A

    2012-10-01

    Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.

  1. Estimated risks and optimistic self-perception of breast cancer risk in Korean women.

    Science.gov (United States)

    Chung, ChaeWeon; Lee, Suk Jeong

    2013-11-01

    To determine women's perceived personal and comparative risks of breast cancer, and to examine the relationships with risk factors. Despite the increasing incidence of breast cancer in younger women and the availability of screening, women's health behaviors have not advanced accordingly. A cross-sectional survey design utilized a convenience sample of 222 women in their 30s and 40s recruited from community settings in Seoul. Self-administered questionnaire data were analyzed by descriptive statistics, the chi-squared test, and ANOVA. Risk perception levels differed significantly by breast cancer risk factors. Half of the women were optimistic about their breast cancer risk, while perceived personal risk did not reflect women's own risk factors and comparative risk differed only by the practice of clinical breast exam. Women's knowledge and awareness of their breast cancer risk factors need to be improved for appropriate risk perception and health behaviors, and accurate risk estimation could be utilized to educate them in clinical settings. © 2013.

  2. Gene panel testing for inherited cancer risk.

    Science.gov (United States)

    Hall, Michael J; Forman, Andrea D; Pilarski, Robert; Wiesner, Georgia; Giri, Veda N

    2014-09-01

    Next-generation sequencing technologies have ushered in the capability to assess multiple genes in parallel for genetic alterations that may contribute to inherited risk for cancers in families. Thus, gene panel testing is now an option in the setting of genetic counseling and testing for cancer risk. This article describes the many gene panel testing options clinically available to assess inherited cancer susceptibility, the potential advantages and challenges associated with various types of panels, clinical scenarios in which gene panels may be particularly useful in cancer risk assessment, and testing and counseling considerations. Given the potential issues for patients and their families, gene panel testing for inherited cancer risk is recommended to be offered in conjunction or consultation with an experienced cancer genetic specialist, such as a certified genetic counselor or geneticist, as an integral part of the testing process. Copyright © 2014 by the National Comprehensive Cancer Network.

  3. Low Dose Radiation Cancer Risks: Epidemiological and Toxicological Models

    Energy Technology Data Exchange (ETDEWEB)

    David G. Hoel, PhD

    2012-04-19

    The basic purpose of this one year research grant was to extend the two stage clonal expansion model (TSCE) of carcinogenesis to exposures other than the usual single acute exposure. The two-stage clonal expansion model of carcinogenesis incorporates the biological process of carcinogenesis, which involves two mutations and the clonal proliferation of the intermediate cells, in a stochastic, mathematical way. The current TSCE model serves a general purpose of acute exposure models but requires numerical computation of both the survival and hazard functions. The primary objective of this research project was to develop the analytical expressions for the survival function and the hazard function of the occurrence of the first cancer cell for acute, continuous and multiple exposure cases within the framework of the piece-wise constant parameter two-stage clonal expansion model of carcinogenesis. For acute exposure and multiple exposures of acute series, it is either only allowed to have the first mutation rate vary with the dose, or to have all the parameters be dose dependent; for multiple exposures of continuous exposures, all the parameters are allowed to vary with the dose. With these analytical functions, it becomes easy to evaluate the risks of cancer and allows one to deal with the various exposure patterns in cancer risk assessment. A second objective was to apply the TSCE model with varing continuous exposures from the cancer studies of inhaled plutonium in beagle dogs. Using step functions to estimate the retention functions of the pulmonary exposure of plutonium the multiple exposure versions of the TSCE model was to be used to estimate the beagle dog lung cancer risks. The mathematical equations of the multiple exposure versions of the TSCE model were developed. A draft manuscript which is attached provides the results of this mathematical work. The application work using the beagle dog data from plutonium exposure has not been completed due to the fact

  4. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Kikuta, Kazuhiro; Masamune, Atsushi; Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi; Egawa, Shinichi; Unno, Michiaki; Shimosegawa, Tooru

    2010-01-01

    Research highlights: → Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. → Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. → PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. → This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated β-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered by treatment with anti

  5. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  6. Cancer stem cells and personalized cancer nanomedicine.

    Science.gov (United States)

    Gener, Petra; Rafael, Diana Fernandes de Sousa; Fernández, Yolanda; Ortega, Joan Sayós; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo

    2016-02-01

    Despite the progress in cancer treatment over the past years advanced cancer is still an incurable disease. Special attention is pointed toward cancer stem cell (CSC)-targeted therapies, because this minor cell population is responsible for the treatment resistance, metastatic growth and tumor recurrence. The recently described CSC dynamic phenotype and interconversion model of cancer growth hamper even more the possible success of current cancer treatments in advanced cancer stages. Accordingly, CSCs can be generated through dedifferentiation processes from non-CSCs, in particular, when CSC populations are depleted after treatment. In this context, the use of targeted CSC nanomedicines should be considered as a promising tool to increase CSC sensitivity and efficacy of specific anti-CSC therapies.

  7. Familial risks in testicular cancer as aetiological clues.

    Science.gov (United States)

    Hemminki, Kari; Chen, Bowang

    2006-02-01

    We used the nationwide Swedish Family-Cancer Database to analyse the risk for testicular cancer in offspring through parental and sibling probands. Among 0 to 70-year-old offspring, 4,586 patients had testicular cancer. Standardized incidence ratios for familial risk were 3.8-fold when a father and 7.6-fold when a brother had testicular cancer. Testicular cancer was associated with leukaemia, distal colon and kidney cancer, melanoma, connective tissue tumours and lung cancer in families. Non-seminoma was associated with maternal lung cancer but the risk was highest for the late-onset cases, providing no support to the theory of the in utero effect of maternal smoking on the son's risk of testicular cancer. However, the theory cannot be excluded but should be taken up for study when further data are available on maternal smoking. The high familial risk may be the product of shared childhood environment and heritable causes.

  8. Establishing a family risk assessment clinic for breast cancer.

    LENUS (Irish Health Repository)

    Mulsow, Jurgen

    2012-02-01

    Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15-20% of women who develop breast cancer have a family history and 5-10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score >or=16. BRCA1\\/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management.

  9. Risk determination and prevention of breast cancer.

    Science.gov (United States)

    Howell, Anthony; Anderson, Annie S; Clarke, Robert B; Duffy, Stephen W; Evans, D Gareth; Garcia-Closas, Montserat; Gescher, Andy J; Key, Timothy J; Saxton, John M; Harvie, Michelle N

    2014-09-28

    Breast cancer is an increasing public health problem. Substantial advances have been made in the treatment of breast cancer, but the introduction of methods to predict women at elevated risk and prevent the disease has been less successful. Here, we summarize recent data on newer approaches to risk prediction, available approaches to prevention, how new approaches may be made, and the difficult problem of using what we already know to prevent breast cancer in populations. During 2012, the Breast Cancer Campaign facilitated a series of workshops, each covering a specialty area of breast cancer to identify gaps in our knowledge. The risk-and-prevention panel involved in this exercise was asked to expand and update its report and review recent relevant peer-reviewed literature. The enlarged position paper presented here highlights the key gaps in risk-and-prevention research that were identified, together with recommendations for action. The panel estimated from the relevant literature that potentially 50% of breast cancer could be prevented in the subgroup of women at high and moderate risk of breast cancer by using current chemoprevention (tamoxifen, raloxifene, exemestane, and anastrozole) and that, in all women, lifestyle measures, including weight control, exercise, and moderating alcohol intake, could reduce breast cancer risk by about 30%. Risk may be estimated by standard models potentially with the addition of, for example, mammographic density and appropriate single-nucleotide polymorphisms. This review expands on four areas: (a) the prediction of breast cancer risk, (b) the evidence for the effectiveness of preventive therapy and lifestyle approaches to prevention, (c) how understanding the biology of the breast may lead to new targets for prevention, and (d) a summary of published guidelines for preventive approaches and measures required for their implementation. We hope that efforts to fill these and other gaps will lead to considerable advances in our

  10. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    International Nuclear Information System (INIS)

    Heck, Julia E.; Moore, Lee E.; Lee, Yuan-Chin A.; McKay, James D.; Hung, Rayjean J.; Karami, Sara; Gaborieau, Valérie; Szeszenia-Dabrowska, Neonila; Zaridze, David G.; Mukeriya, Anush; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Kollárová, Helena; Bencko, Vladimir; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Boffetta, Paolo

    2012-01-01

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  11. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Heck, Julia E. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); Moore, Lee E. [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Lee, Yuan-Chin A. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); McKay, James D. [International Agency for Research on Cancer, Lyon (France); Hung, Rayjean J. [Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON (Canada); Karami, Sara [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Gaborieau, Valérie [International Agency for Research on Cancer, Lyon (France); Szeszenia-Dabrowska, Neonila [Department of Epidemiology, Institute of Occupational Medicine, Lodz (Poland); Zaridze, David G. [Cancer Research Centre, Institute of Carcinogenesis, Moscow (Russian Federation); Mukeriya, Anush [Cancer Research Centre, Department of Epidemiology, Moscow (Russian Federation); Mates, Dana [Institute of Public Health, Bucharest (Romania); Foretova, Lenka [Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno (Czech Republic); Janout, Vladimir; Kollárová, Helena [Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc (Czech Republic); Bencko, Vladimir [First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague, Prague, Czech Republic (Czech Republic); Rothman, Nathaniel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Brennan, Paul [International Agency for Research on Cancer, Lyon (France); Chow, Wong-Ho [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Boffetta, Paolo, E-mail: paolo.boffetta@mssm.edu [International Prevention Research Institute, Lyon (France); Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, NY (United States)

    2012-02-20

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  12. Impact of types of lymphocyte chromosomal aberrations on human cancer risk

    DEFF Research Database (Denmark)

    Hagmar, Lars; Strömberg, Ulf; Bonassi, Stefano

    2004-01-01

    The frequency of cells with structural chromosomal aberrations (CAs) in peripheral blood lymphocytes is the first genotoxicity biomarker that has shown an association with cancer risk. CAs are usually divided into chromosome-type (CSAs) and chromatid-type aberrations (CTAs), with different mechan...

  13. Abortion, Miscarriage, and Breast Cancer Risk

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... interactions of pregnancy-related mammotrophic factors, ligands, and receptors? What is the time course of pregnancy-related ...

  14. Low-risk factor profile, estrogen levels, and breast cancer risk among postmenopausal women

    DEFF Research Database (Denmark)

    Rod, Naja Hulvej; Hansen, Ase Marie; Nielsen, Jens

    2008-01-01

    Obesity, alcohol consumption, physical inactivity and postmenopausal hormone use are known modifiable risk factors for breast cancer. We aim to measure incidence rates of breast cancer for women with favorable levels on all 4 risk factors (BMI......Obesity, alcohol consumption, physical inactivity and postmenopausal hormone use are known modifiable risk factors for breast cancer. We aim to measure incidence rates of breast cancer for women with favorable levels on all 4 risk factors (BMI...

  15. Does Metformin Reduce Cancer Risks? Methodologic Considerations.

    Science.gov (United States)

    Golozar, Asieh; Liu, Shuiqing; Lin, Joeseph A; Peairs, Kimberly; Yeh, Hsin-Chieh

    2016-01-01

    The substantial burden of cancer and diabetes and the association between the two conditions has been a motivation for researchers to look for targeted strategies that can simultaneously affect both diseases and reduce their overlapping burden. In the absence of randomized clinical trials, researchers have taken advantage of the availability and richness of administrative databases and electronic medical records to investigate the effects of drugs on cancer risk among diabetic individuals. The majority of these studies suggest that metformin could potentially reduce cancer risk. However, the validity of this purported reduction in cancer risk is limited by several methodological flaws either in the study design or in the analysis. Whether metformin use decreases cancer risk relies heavily on the availability of valid data sources with complete information on confounders, accurate assessment of drug use, appropriate study design, and robust analytical techniques. The majority of the observational studies assessing the association between metformin and cancer risk suffer from methodological shortcomings and efforts to address these issues have been incomplete. Future investigations on the association between metformin and cancer risk should clearly address the methodological issues due to confounding by indication, prevalent user bias, and time-related biases. Although the proposed strategies do not guarantee a bias-free estimate for the association between metformin and cancer, they will reduce synthesis of and reporting of erroneous results.

  16. Cancer vaccine development: Designing tumor cells for greater immunogenicity

    Science.gov (United States)

    Bozeman, Erica N.; Shashidharamurthy, Rangaiah; Paulos, Simon A.; Palaniappan, Ravi; D’Souza, Martin; Selvaraj, Periasamy

    2014-01-01

    Cancer vaccine development is one of the most hopeful and exhilarating areas in cancer research. For this reason, there has been a growing interest in the development and application of novel immunotherapies for the treatment of cancer with the focus being on stimulating the immune system to target tumor cells specifically while leaving normal cells unharmed. From such research has emerged a host of promising immunotherapies such as dendritic cell-based vaccines, cytokine therapies and gene transfer technology. These therapies seek to counteract the poor immunogenicity of tumors by augmenting the host’s immune system with a variety of immunostimulatory proteins such as cytokines and costimulatory molecules. While such therapies have proven effective in the induction of anti-tumor immunity in animal models, they are less than optimal and pose a high risk of clinical infeasibility. Herein, we further discuss these immunotherapies as well as a feasible and efficient alternative that, in pre-clinical animal models, allows for the expression of specific immunostimulatory molecules on the surface of tumor cells by a novel protein transfer technology. PMID:20036822

  17. Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression.

    Science.gov (United States)

    Lopes-Coelho, Filipa; Gouveia-Fernandes, Sofia; Serpa, Jacinta

    2018-02-01

    The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

  18. Gynecologic cancer treatment: risk factors for therapeutically induced neoplasia

    International Nuclear Information System (INIS)

    Messerschmidt, G.L.; Hoover, R.; Young, R.C.

    1981-01-01

    Therapeutic intervention in a course of illness, while producing the desired result, also may have some adverse long-term effects on the patient. Second malignancies are one of the known complications of therapy. The treatments of gynecologic cancers by surgery, irradiation and chemotherapy have been associated with subsequent neoplasms. Care must be exercised in associating previous therapy and a subsequent malignancy. Naturally occurring second cancers must be separated from those which are iatrogenic. Associations in the literature have been made involving malignancies as a sequelae of prior gynecologic therapy. The use of normal skin from the thigh to fabricate an artificial vagina has resulted in more squamous cell carcinomas than expected. Alkylating agents used in the treatment of ovarian cancer and other diseases have been shown to lead to an increased risk of leukemia. Irradiation therapy, however, has not yet been shown to be related to leukemia in cervical cancer patients. The incidence of lymphoma and uterine, urinary bladder and colon carcinomas has been associated with prior irradiation for gynecologic disease. The literature regarding the therapeutically induced risk factors in gynecologic therapy is reviewed and areas of our knowledge that require more investigation are identified

  19. Non-melanoma skin cancer: occupational risk from UV light and arsenic exposure.

    Science.gov (United States)

    Surdu, Simona

    2014-01-01

    Non-melanoma skin cancer (NMSC) has a significant impact on public health and health care costs as a result of high morbidity and disfigurement due to the destruction of surrounding tissues. Although the mortality rates of these tumors are low, the high incidence rates determine a considerable number of deaths. NMSC is the most common type of skin cancer, representing about 1/3 of all malignancies diagnosed worldwide each year. The most common NMSC are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Studies on humans and experimental animals indicate that ultraviolet (UV) light and arsenic play important roles in the development of these skin malignancies. Several epidemiological studies have investigated the risk of developing NMSC and the potential link between exposure to sunlight and arsenic in the agricultural and industrial occupational settings. To date, the published literature suggests that there is no apparent skin cancer risk as regards workplace exposure to artificial UV light or arsenic. Concerning UV light from sun exposure at the workplace, most published studies indicated an elevated risk for SCC, but are less conclusive for BCC. Many of these studies are limited by the methodology used in the evaluation of occupational exposure and the lack of adjustment for major confounders. Therefore, further epidemiological studies are required to focus on exposure assessment at the individual level as well as potential interactions with other occupational and non-occupational exposures and individual susceptibility. In doing so, we can better quantify the true risk of skin cancer in exposed workers and inform effective public health prevention programs.

  20. Radiation risk from CT: implications for cancer screening.

    Science.gov (United States)

    Albert, Jeffrey M

    2013-07-01

    The cancer risks associated with patient exposure to radiation from medical imaging have become a major topic of debate. The higher doses necessary for technologies such as CT and the increasing utilization of these technologies further increase medical radiation exposure to the population. Furthermore, the use of CT for population-based cancer screening continues to be explored for common malignancies such as lung cancer and colorectal cancer. Given the known carcinogenic effects of ionizing radiation, this warrants evaluation of the balance between the benefit of early cancer detection and the risk of screening-induced malignancy. This report provides a brief review of the process of radiation carcino-genesis and the literature evaluating the risk of malignancy from CT, with a focus on the risks and benefits of CT for cancer screening. The available data suggest a small but real risk of radiation-induced malignancy from CT that could become significant at the population level with widespread use of CT-based screening. However, a growing body of literature suggests that the benefits of CT screening for lung cancer in high-risk patients and CT colonography for colorectal cancer may significantly outweigh the radiation risk. Future studies evaluating the benefits of CT screening should continue to consider potential radiation risks.

  1. Making sense of cancer risk calculators on the web.

    Science.gov (United States)

    Levy, Andrea Gurmankin; Sonnad, Seema S; Kurichi, Jibby E; Sherman, Melani; Armstrong, Katrina

    2008-03-01

    Cancer risk calculators on the internet have the potential to provide users with valuable information about their individual cancer risk. However, the lack of oversight of these sites raises concerns about low quality and inconsistent information. These concerns led us to evaluate internet cancer risk calculators. After a systematic search to find all cancer risk calculators on the internet, we reviewed the content of each site for information that users should seek to evaluate the quality of a website. We then examined the consistency of the breast cancer risk calculators by having 27 women complete 10 of the breast cancer risk calculators for themselves. We also completed the breast cancer risk calculators for a hypothetical high- and low-risk woman, and compared the output to Surveillance Epidemiology and End Results estimates for the average same-age and same-race woman. Nineteen sites were found, 13 of which calculate breast cancer risk. Most sites do not provide the information users need to evaluate the legitimacy of a website. The breast cancer calculator sites vary in the risk factors they assess to calculate breast cancer risk, how they operationalize each risk factor and in the risk estimate they provide for the same individual. Internet cancer risk calculators have the potential to provide a public health benefit by educating individuals about their risks and potentially encouraging preventive health behaviors. However, our evaluation of internet calculators revealed several problems that call into question the accuracy of the information that they provide. This may lead the users of these sites to make inappropriate medical decisions on the basis of misinformation.

  2. Evaluation of the Prostate Cancer Prevention Trial Risk Calculator in a High-Risk Screening Population

    Science.gov (United States)

    Kaplan, David J.; Boorjian, Stephen A.; Ruth, Karen; Egleston, Brian L.; Chen, David Y.T.; Viterbo, Rosalia; Uzzo, Robert G.; Buyyounouski, Mark K.; Raysor, Susan; Giri, Veda N.

    2009-01-01

    Introduction Clinical factors in addition to PSA have been evaluated to improve risk assessment for prostate cancer. The Prostate Cancer Prevention Trial (PCPT) risk calculator provides an assessment of prostate cancer risk based on age, PSA, race, prior biopsy, and family history. This study evaluated the risk calculator in a screening cohort of young, racially diverse, high-risk men with a low baseline PSA enrolled in the Prostate Cancer Risk Assessment Program. Patients and Methods Eligibility for PRAP include men ages 35-69 who are African-American, have a family history of prostate cancer, or have a known BRCA1/2 mutation. PCPT risk scores were determined for PRAP participants, and were compared to observed prostate cancer rates. Results 624 participants were evaluated, including 382 (61.2%) African-American men and 375 (60%) men with a family history of prostate cancer. Median age was 49.0 years (range 34.0-69.0), and median PSA was 0.9 (range 0.1-27.2). PCPT risk score correlated with prostate cancer diagnosis, as the median baseline risk score in patients diagnosed with prostate cancer was 31.3%, versus 14.2% in patients not diagnosed with prostate cancer (p<0.0001). The PCPT calculator similarly stratified the risk of diagnosis of Gleason score ≥7 disease, as the median risk score was 36.2% in patients diagnosed with Gleason ≥7 prostate cancer versus 15.2% in all other participants (p<0.0001). Conclusion PCPT risk calculator score was found to stratify prostate cancer risk in a cohort of young, primarily African-American men with a low baseline PSA. These results support further evaluation of this predictive tool for prostate cancer risk assessment in high-risk men. PMID:19709072

  3. ATM variants and cancer risk in breast cancer patients from Southern Finland

    Directory of Open Access Journals (Sweden)

    Aittomäki Kristiina

    2006-08-01

    Full Text Available Abstract Background Individuals heterozygous for germline ATM mutations have been reported to have an increased risk for breast cancer but the role for ATM genetic variants for breast cancer risk has remained unclear. Recently, a common ATM variant, ATMivs38 -8T>C in cis with the ATMex39 5557G>A (D1853N variant, was suggested to associate with bilateral breast cancer among familial breast cancer patients from Northern Finland. We have here evaluated the 5557G>A and ivs38-8T>C variants in an extensive case-control association analysis. We also aimed to investigate whether there are other ATM mutations or variants contributing to breast cancer risk in our population. Methods Two common ATM variants, 5557G>A and ivs38-8T>C, previously suggested to associate with bilateral breast cancer, were genotyped in an extensive set of 786 familial and 884 unselected breast cancer cases as well as 708 healthy controls. We also screened the entire coding region and exon-intron boundaries of the ATM gene in 47 familial breast cancer patients and constructed haplotypes of the patients. The identified variants were also evaluated for increased breast cancer risk among additional breast cancer cases and controls. Results Neither of the two common variants, 5557G>A and ivs38-8T>C, nor any haplotype containing them, was significantly associated with breast cancer risk, bilateral breast cancer or multiple primary cancers in any of the patient groups or subgoups. Three rare missense alterations and one intronic change were each found in only one patient of over 250 familial patients studied and not among controls. The fourth missense alteration studied further was found with closely similar frequencies in over 600 familial cases and controls. Conclusion Altogether, our results suggest very minor effect, if any, of ATM genetic variants on familial breast cancer in Southern Finland. Our results do not support association of the 5557G>A or ivs38-8T>C variant with

  4. Adipocyte activation of cancer stem cell signaling in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2015-01-01

    Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

  5. Review of radon and lung cancer risk

    International Nuclear Information System (INIS)

    Samet, J.M.; Hornung, R.W.

    1990-01-01

    Radon, a long-established cause of lung cancer in uranium and other underground miners, has recently emerged as a potentially important cause of lung cancer in the general population. The evidence for widespread exposure of the population to radon and the well-documented excess of lung cancer among underground miners exposed to radon decay products have raised concern that exposure to radon progeny might also be a cause of lung cancer in the general population. To date, epidemiological data on the lung cancer risk associated with environmental exposure to radon have been limited. Consequently, the lung cancer hazard posed by radon exposure in indoor air has been addressed primarily through risk estimation procedures. The quantitative risks of lung cancer have been estimated using exposure-response relations derived from the epidemiological investigations of uranium and other underground miners. We review five of the more informative studies of miners and recent risk projection models for excess lung cancer associated with radon. The principal models differ substantially in their underlying assumptions and consequently in the resulting risk projections. The resulting diversity illustrates the substantial uncertainty that remains concerning the most appropriate model of the temporal pattern of radon-related lung cancer. Animal experiments, further follow-up of the miner cohorts, and well-designed epidemiological studies of indoor exposure should reduce this uncertainty. 18 references

  6. Parity and risk of lung cancer in women.

    Science.gov (United States)

    Paulus, Jessica K; Asomaning, Kofi; Kraft, Peter; Johnson, Bruce E; Lin, Xihong; Christiani, David C

    2010-03-01

    Patterns of lung cancer incidence suggest that gender-associated factors may influence lung cancer risk. Given the association of parity with risk of some women's cancers, the authors hypothesized that childbearing history may also be associated with lung cancer. Women enrolled in the Lung Cancer Susceptibility Study at Massachusetts General Hospital (Boston, Massachusetts) between 1992 and 2004 (1,004 cases, 848 controls) were available for analysis of the association between parity and lung cancer risk. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. After results were controlled for age and smoking history, women with at least 1 child had 0.71 times the odds of lung cancer as women without children (odds ratio = 0.71, 95% confidence interval: 0.52, 0.97). A significant linear trend was found: Lung cancer risk decreased with increasing numbers of children (P < 0.001). This inverse association was stronger in never smokers (P = 0.12) and was limited to women over age 50 years at diagnosis (P = 0.17). Age at first birth was not associated with risk. The authors observed a protective association between childbearing and lung cancer, adding to existing evidence that reproductive factors may moderate lung cancer risk in women.

  7. Increased pancreatic cancer risk following radiotherapy for testicular cancer.

    Science.gov (United States)

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S; Stovall, Marilyn; van Leeuwen, Flora E; Rajaraman, Preetha; Smith, Susan A; Weathers, Rita E; Aleman, Berthe M P; Andersson, Michael; Curtis, Rochelle E; Dores, Graça M; Fraumeni, Joseph F; Hall, Per; Holowaty, Eric J; Joensuu, Heikki; Kaijser, Magnus; Kleinerman, Ruth A; Langmark, Frøydis; Lynch, Charles F; Pukkala, Eero; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Morton, Lindsay M; Fossa, Sophie D; Travis, Lois B

    2016-09-27

    Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trendcancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

  8. Chronic obstructive pulmonary disease and cancer risk

    DEFF Research Database (Denmark)

    Kornum, Jette Brommann; Sværke, Claus; Thomsen, Reimar Wernich

    2012-01-01

    Little is known about the risk of cancer in patients with chronic obstructive pulmonary disease (COPD), including which cancer sites are most affected. We examined the short- and long-term risk of lung and extrapulmonary cancer in a nationwide cohort of COPD patients....

  9. Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers.

    Science.gov (United States)

    Borges, Álvaro H; Silverberg, Michael J; Wentworth, Deborah; Grulich, Andrew E; Fätkenheuer, Gerd; Mitsuyasu, Ronald; Tambussi, Giuseppe; Sabin, Caroline A; Neaton, James D; Lundgren, Jens D

    2013-06-01

    To investigate the relationship between inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)] and coagulation (D-dimer) biomarkers and cancer risk during HIV infection. A prospective cohort. HIV-infected patients on continuous antiretroviral therapy (ART) in the control arms of three randomized trials (N=5023) were included in an analysis of predictors of cancer (any type, infection-related or infection-unrelated). Hazard ratios for IL-6, CRP and D-dimer levels (log2-transformed) were calculated using Cox models stratified by trial and adjusted for demographics and CD4+ cell counts and adjusted also for all biomarkers simultaneously. To assess the possibility that biomarker levels were elevated at entry due to undiagnosed cancer, analyses were repeated excluding early cancer events (i.e. diagnosed during first 2 years of follow-up). During approximately 24,000 person-years of follow-up (PYFU), 172 patients developed cancer (70 infection-related; 102 infection-unrelated). The risk of developing cancer was associated with higher levels (per doubling) of IL-6 (hazard ratio 1.38, Passociated with cancer risk when all biomarkers were considered simultaneously. Results for infection-related and infection-unrelated cancers were similar to results for any cancer. Hazard ratios excluding 69 early cancer events were 1.31 (P=0.007), 1.14 (P=0.02) and 1.07 (P=0.49) for IL-6, CRP and D-dimer, respectively. Activated inflammation and coagulation pathways are associated with increased cancer risk during HIV infection. This association was stronger for IL-6 and persisted after excluding early cancer. Trials of interventions may be warranted to assess whether cancer risk can be reduced by lowering IL-6 levels in HIV-positive individuals.

  10. Gastric stem cells and gastric cancer stem cells

    OpenAIRE

    Han, Myoung-Eun; Oh, Sae-Ock

    2013-01-01

    The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal ev...

  11. Multimodal Nanomedicine Strategies for Targeting Cancer Cells as well as Cancer Stem Cell Signalling Mechanisms.

    Science.gov (United States)

    Kanwar, Jagat R; Samarasinghe, Rasika M; Kamalapuram, Sishir K; Kanwar, Rupinder K

    2017-01-01

    Increasing evidence suggests that stem cells, a small population of cells with unique selfrenewable and tumour regenerative capacity, are aiding tumour re-growth and multidrug resistance. Conventional therapies are highly ineffective at eliminating these cells leading to relapse of disease and formation of chemoresistance tumours. Cancer and stem cells targeted therapies that utilizes nanotherapeutics to delivery anti-cancer drugs to specific sites are continuously investigated. This review focuses on recent research using nanomedicine and targeting entities to eliminate cancer cells and cancer stem cells. Current nanotherapeutics in clinical trials along with more recent publications on targeted therapies are addressed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...... offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models...

  13. Risk of prostate cancer among cancer survivors in the Netherlands

    NARCIS (Netherlands)

    Kok, D.E.G.; Schans, van de S.A.; Liu, L.; Kampman, E.; Coebergh, J.W.; Kiemeney, L.A.; Soerjomataram, I.; Aben, K.K.

    2013-01-01

    In parallel with increasing numbers of cancer patients and improving cancer survival, the occurrence of second primary cancers becomes a relevant issue. The aim of our study was to evaluate risk of prostate cancer as second primary cancer in a population-based setting. Methods Data from the

  14. Human Papillomavirus Infections and Cancer Stem Cells of Tumors from the Uterine Cervix

    Science.gov (United States)

    López, Jacqueline; Ruíz, Graciela; Organista-Nava, Jorge; Gariglio, Patricio; García-Carrancá, Alejandro

    2012-01-01

    Different rate of development of productive infections (as low grade cervical intraepithelial neoplasias), or high grade lesions and cervical malignant tumors associated with infections of the Transformation zone (TZ) by High-Risk Human Papillomavirus (HR-HPV), could suggest that different epithelial host target cells could exist. If there is more than one target cell, their differential infection by HR-HPV may play a central role in the development of cervical cancer. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support in several solid tumors, including cervical cancer (CC). According to the cancer stem cell (CSC) hypothesis, CC can now be considered a disease in which stem cells of the TZ are converted to cervical cancer stem cells by the interplay between HR-HPV viral oncogenes and cellular alterations that are thought to be finally responsible for tumor initiation and maintenance. Current studies of CSC could provide novel insights regarding tumor initiation and progression, their relation with viral proteins and interplay with the tumor micro-environment. This review will focus on the biology of cervical cancer stem cells, which might contribute to our understanding of the mechanisms responsible for cervical tumor development. PMID:23341858

  15. Management of low (favourable)-risk prostate cancer.

    Science.gov (United States)

    Carter, H Ballentine

    2011-12-01

    What's known on the subject? and What does the study add? Most men who are diagnosed with favourable-risk prostate cancer undergo some form of active intervention, despite evidence that treatment will not improve health outcomes for many. The decision to undergo treatment after diagnosis is, in part, related to the inability to precisely determine the long-term risk of harm without treatment. Nevertheless, physicians should consider patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments, before recommending a management option. This is especially important for older men, given the high level of evidence that those with low-risk disease are unlikely to accrue any benefit from curative intervention. What is known on the subject: Over treatment of favourable-risk prostate cancer is common, especially among older men. What does the study add: A review of the natural history of favourable-risk prostate cancer in the context of choices for management of the disease. • The management of favourable-risk prostate cancer is controversial, and in the absence of controlled trials to inform best practice, choices are driven by personal beliefs with resultant wide variation in practice patterns. • Men with favourable-risk prostate cancer diagnosed today often undergo treatments that will not improve overall health outcomes. • A shared-decision approach for selecting optimal management of favourable-risk disease should account for patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments. © 2011 THE AUTHOR. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  16. Fertility drugs, reproductive strategies and ovarian cancer risk.

    Science.gov (United States)

    Tomao, Federica; Lo Russo, Giuseppe; Spinelli, Gian Paolo; Stati, Valeria; Prete, Alessandra Anna; Prinzi, Natalie; Sinjari, Marsela; Vici, Patrizia; Papa, Anselmo; Chiotti, Maria Stefania; Benedetti Panici, Pierluigi; Tomao, Silverio

    2014-01-01

    Several adverse effects have been related to infertility treatments, such as cancer development. In particular, the relationship between infertility, reproductive strategies, and risk of gynecological cancers has aroused much interest in recent years. The evaluation of cancer risk among women treated for infertility is very complex, mainly because of many factors that can contribute to occurrence of cancer in these patients (including parity status). This article addresses the possible association between the use of fertility treatments and the risk of ovarian cancer, through a scrupulous search of the literature published thus far in this field. Our principal objective was to give more conclusive answers on the question whether the use of fertility drug significantly increases ovarian cancer risk. Our analysis focused on the different types of drugs and different treatment schedules used. This study provides additional insights regarding the long-term relationships between fertility drugs and risk of ovarian cancer.

  17. Cancer Stem Cells in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J., E-mail: christiane.bruns@med.uni-muenchen.de [Department of Surgery, Ludwig Maximilian University of Munich, Klinikum Grosshadern, Marchioninistr. 15, D-81377, Munich (Germany)

    2010-08-19

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  18. Genetic Variants in Epigenetic Pathways and Risks of Multiple Cancers in the GAME-ON Consortium.

    Science.gov (United States)

    Toth, Reka; Scherer, Dominique; Kelemen, Linda E; Risch, Angela; Hazra, Aditi; Balavarca, Yesilda; Issa, Jean-Pierre J; Moreno, Victor; Eeles, Rosalind A; Ogino, Shuji; Wu, Xifeng; Ye, Yuanqing; Hung, Rayjean J; Goode, Ellen L; Ulrich, Cornelia M

    2017-06-01

    Background: Epigenetic disturbances are crucial in cancer initiation, potentially with pleiotropic effects, and may be influenced by the genetic background. Methods: In a subsets (ASSET) meta-analytic approach, we investigated associations of genetic variants related to epigenetic mechanisms with risks of breast, lung, colorectal, ovarian and prostate carcinomas using 51,724 cases and 52,001 controls. False discovery rate-corrected P values (q values cancer type. For example, variants in BABAM1 were confirmed as a susceptibility locus for squamous cell lung, overall breast, estrogen receptor (ER)-negative breast, and overall prostate, and overall serous ovarian cancer; the most significant variant was rs4808076 [OR = 1.14; 95% confidence interval (CI) = 1.10-1.19; q = 6.87 × 10 -5 ]. DPF1 rs12611084 was inversely associated with ER-negative breast, endometrioid ovarian, and overall and aggressive prostate cancer risk (OR = 0.93; 95% CI = 0.91-0.96; q = 0.005). Variants in L3MBTL3 were associated with colorectal, overall breast, ER-negative breast, clear cell ovarian, and overall and aggressive prostate cancer risk (e.g., rs9388766: OR = 1.06; 95% CI = 1.03-1.08; q = 0.02). Variants in TET2 were significantly associated with overall breast, overall prostate, overall ovarian, and endometrioid ovarian cancer risk, with rs62331150 showing bidirectional effects. Analyses of subpathways did not reveal gene subsets that contributed disproportionately to susceptibility. Conclusions: Functional and correlative studies are now needed to elucidate the potential links between germline genotype, epigenetic function, and cancer etiology. Impact: This approach provides novel insight into possible pleiotropic effects of genes involved in epigenetic processes. Cancer Epidemiol Biomarkers Prev; 26(6); 816-25. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Racial/Ethnic Differences in Cancer Risk After Kidney Transplantation

    Science.gov (United States)

    Hall, EC; Segev, DL; Engels, EA

    2014-01-01

    Transplant recipients have elevated cancer risk, but it is unknown if cancer risk differs across race and ethnicity as in the general population. U.S. kidney recipients (N=87,895) in the Transplant Cancer Match Study between 1992 and 2008 were evaluated for racial/ethnic differences in risk for six common cancers after transplantation. Compared to white recipients, black recipients had lower incidence of non-Hodgkin lymphoma (NHL) (adjusted incidence rate ratio [aIRR] 0.60, pkidney (aIRR 2.09, pcancer (aIRR 2.14, pcancer (aIRR 0.72, p=0.05). Colorectal cancer incidence was similar across groups. Standardized incidence ratios (SIRs) measured the effect of transplantation on cancer risk and were similar for most cancers (p≥0.1). However, black and Hispanic recipients had larger increases in kidney cancer risk with transplantation (SIRs: 8.96 in blacks, 5.95 in Hispanics vs. 4.44 in whites), and only blacks had elevated prostate cancer risk following transplantation (SIR: 1.21). Racial/ethnic differences in cancer risk after transplantation mirror general population patterns, except for kidney and prostate cancers where differences reflect the effects of end-stage renal disease or transplantation. PMID:23331953

  20. Cancer stem cells in colorectal cancer: a review.

    Science.gov (United States)

    Munro, Matthew J; Wickremesekera, Susrutha K; Peng, Lifeng; Tan, Swee T; Itinteang, Tinte

    2018-02-01

    Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men. Adenocarcinoma accounts for 90% of CRC cases. There has been accumulating evidence in support of the cancer stem cell (CSC) concept of cancer which proposes that CSCs are central in the initiation of cancer. CSCs have been the focus of study in a range of cancers, including CRC. This has led to the identification and understanding of genes involved in the induction and maintenance of pluripotency of stem cells, and markers for CSCs, including those investigated specifically in CRC. Knowledge of the expression pattern of CSCs in CRC has been increasing in recent years, revealing a heterogeneous population of cells within CRC ranging from pluripotent to differentiated cells, with overlapping and sometimes unique combinations of markers. This review summarises current literature on the understanding of CSCs in CRC, including evidence of the presence of CSC subpopulations, and the stem cell markers currently used to identify and localise these CSC subpopulations. Future research into this field may lead to improved methods for early detection of CRC, novel therapy and monitoring of treatment for CRC and other cancer types. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Urinary tract cancer and hereditary nonpolyposis colorectal cancer : Risks and screening options

    NARCIS (Netherlands)

    Sijmons, RH; Kiemeney, LALM; Witjes, JA; Vasen, HFA

    Purpose: We investigate the risk of the different types of urinary tract cancer in hereditary nonpolyposis colorectal cancer families and review screening options. Materials and Methods: We retrospectively calculated the relative and cumulative risks of developing urinary tract cancer by comparing

  2. Perceptions of Risk of Developing Skin Cancer for Diverse Audiences: Enhancing Relevance of Sun Protection to Reduce the Risk

    OpenAIRE

    Robinson, June K.; Friedewald, John; Gordon, Elisa J.

    2016-01-01

    Sixty-five percent of kidney transplant recipients (KTRs) develop squamous cell carcinoma (SCC). Perceptions of risk of developing skin cancer, amelioration of this risk with sun protection, and having choices among sun protection strategies may enhance sun protection use by KTRS, who are at greater risk than the general population. Thirty KTRs stratified among non-Hispanic Whites, non-Hispanic Blacks, and Hispanic/Latinos evaluated three versions of the interactive, web-based, electronic sun...

  3. Night shift work and prolactin as a breast cancer risk factor

    Directory of Open Access Journals (Sweden)

    Agnieszka Bukowska

    2013-04-01

    Full Text Available Prolactin - a hormone secreted in a circadian rhythm acts as a regulator of growth and development of the mammary glands. It has been observed that working at night increases breast cancer risk in women. Night shift work, probably carcinogenic to humans (Group 2A IARC, can disrupt a circadian rhythm, and thus potentially alter the rhythm of prolactin secretion. The aim of our work was to review epidemiological evidence on the association between prolactin and the risk of breast cancer and the influence of work at night on prolactin secretion. Search was done in the Medline database by keywords (shift work, work at night, risk of breast cancer and prolactin. The increased proliferation of breast cells activated by prolactin can promote the development of cancer. The results of the largest epidemiological prospective studies suggest the association between prolactin levels and the risk of breast cancer in women. So far, only seven studies have investigated the association between work at night and prolactin secretion. In three studies lower concentrations of prolactin have been observed in night shift workers. No relationship between the night shift work duration and prolactin level in women have been reported. Night shift work can modify the profile of prolactin secretion in night workers, probably decreasing the secretion of this hormone at night. It is therefore unlikely that prolactin plays an important role in the development of breast cancer in women working at night. This conclusion is based on the results of a few epidemiological studies. Med Pr 2013;64(2:245–257

  4. Cancer risk among atomic bomb survivors

    International Nuclear Information System (INIS)

    Schull, W.J.

    1992-01-01

    Continued mortality surveillance and incidence studies have revealed the risk of cancer among the survivors of the atomic bombings of Hiroshima and Nagasaki to increase with increasing dose. Among the sites where the frequency of cancer can be clearly shown to be dose-related are the following: female breast, colon, esophagus, lung, ovary, stomach, thyroid, urinary bladder and leukemia. Although the evidence is less compelling, cancers of the liver, salivary glands, and skin as well as multiple myeloma appear increased too. This increase generally manifests itself when the survivors reach those ages where the natural incidence of cancer begins to rise. Risk is, however, related to the age of the individual at the time of the bombing; the highest risks are associated with individuals who were exposed in the first two decades of life. Current evidence suggests these higher risks decline with increasing time since exposure

  5. Discrepancies between estimated and perceived risk of cancer among individuals with hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Domanska, K; Nilbert, Mef; Soller, M

    2007-01-01

    to individual characteristics. A perceived risk of colorectal cancer above 60% was reported by 22/45 individuals, and only one out of five mutation carriers reported a perceived risk > 80%. Female mutation carriers, individuals below age 50, and individuals who received their oncogenetic counseling within 1......Communicating cancer risk and recommending adequate control programs is central for genetic counseling. Individuals affected by hereditary nonpolyposis colorectal cancer (HNPCC) are at about 80% life-time risk of colorectal cancer and for female carriers 40-60% risk of endometrial cancer and 10...... year prior to the study reported higher, albeit not significantly, perceived risks of colorectal cancer. Higher perceived risks were also reported by individuals who had lost a parent to HNPCC-related cancer at early age, whereas individuals with a personal history of cancer did not report a higher...

  6. Discrepancies between estimated and perceived risk of cancer among individuals with hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Domanska, K; Nilbert, Mef; Soller, M

    2007-01-01

    Communicating cancer risk and recommending adequate control programs is central for genetic counseling. Individuals affected by hereditary nonpolyposis colorectal cancer (HNPCC) are at about 80% life-time risk of colorectal cancer and for female carriers 40-60% risk of endometrial cancer and 10...... to individual characteristics. A perceived risk of colorectal cancer above 60% was reported by 22/45 individuals, and only one out of five mutation carriers reported a perceived risk > 80%. Female mutation carriers, individuals below age 50, and individuals who received their oncogenetic counseling within 1...... year prior to the study reported higher, albeit not significantly, perceived risks of colorectal cancer. Higher perceived risks were also reported by individuals who had lost a parent to HNPCC-related cancer at early age, whereas individuals with a personal history of cancer did not report a higher...

  7. Risk of ovarian cancer in women with first-degree relatives with cancer

    DEFF Research Database (Denmark)

    Soegaard, Marie; Frederiksen, Kirsten; Jensen, Allan

    2009-01-01

    OBJECTIVE: To assess the risk of ovarian cancer in women with first-degree relatives with cancer at one of the four most frequent hereditary sites based on validated cancer diagnoses and to examine the association according to age at diagnosis of ovarian cancer and histology. DESIGN: Case......-control study. SETTING AND POPULATION: First-degree relatives of 554 women with invasive epithelial ovarian cancer and 1,564 controls were included. METHODS: Analyses were performed using multiple logistic regression models. RESULTS: Ovarian cancer in a first-degree relative was significantly associated...... with increased risk of ovarian cancer (OR, 2.4; 95% CI, 1.4-4.1 (mother or sister)). Ovarian cancer in a first-degree relative appeared to be a stronger risk factor for early-onset (cancer than late-onset (OR, 5.3; 95% CI, 2.0-14.1 vs. OR, 1.8; 95% CI, 1.0-3.4). The positive association...

  8. Extragonadal Germ Cell Cancer (EGC)

    Science.gov (United States)

    The Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell tumors. That is, the tumors originate in the sperm forming cells in the testicles ( ...

  9. Immunosuppression and risk of cervical cancer

    DEFF Research Database (Denmark)

    Dugué, Pierre-Antoine; Rebolj, Matejka; Garred, Peter

    2013-01-01

    -stage renal disease seem to be at an increased risk of cervical cancer. A higher risk of cervical precancerous lesions was found in patients with some autoimmune diseases; particularly if treated with immunosuppressants. Among behavioral factors weakening the immune system, smoking appeared to strongly...... increase the risk of cervical cancer, while poor diet only moderately increased the risk. It is difficult to determine whether sexually transmitted infections other than human papillomavirus infection are independent risk factors. Identifying those groups of women likely to fail in clearing persistent...

  10. Allergies and risk of head and neck cancer.

    Science.gov (United States)

    Michaud, Dominique S; Langevin, Scott M; Eliot, Melissa; Nelson, Heather H; McClean, Michael D; Christensen, Brock C; Marsit, Carmen J; Kelsey, Karl T

    2012-08-01

    Individuals with allergies have a heightened Th2 (T helper 2) immunity, which may provide advantages in controlling tumor growth. Inverse associations have been reported among individuals with allergies and risk of brain and pancreatic cancers. We examined the relationship between allergies and risk of head and neck squamous cell carcinoma (HNSCC) in a population-based case-control study with 1,014 cases and 1,193 frequency-matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (95 % CI) controlling for age, sex, race, smoking history, alcohol consumption, and education. In addition, in a subset of the population, models were adjusted for HPV16 status. Individuals with allergies had a 19 % lower risk of HNSCC (OR = 0.81, 95 % CI = 0.67-0.98). Associations with allergies were stronger for laryngeal (OR = 0.66, 95 % CI = 0.45-0.97) and oropharyngeal (OR = 0.73, 95 % CI = 0.57-0.92) cancers, while no association was observed for oral cavity cancers (OR = 0.98, 95 % CI = 0.76-1.26). History of asthma was not associated with overall HNSCC, but the association was statistically significant for oropharyngeal cancer (OR = 0.67, 95 % CI = 0.44-0.99). HPV16 status did not confound or modify the associations with allergies. Elevated Th2 immunity in individuals with history of allergies and asthma may reduce the risk of HNSCC. Additional research into related mechanisms may provide new insights into how to treat HNSCC. These findings may provide new insight into biological pathways that could lead to a better understanding of the etiology of this disease.

  11. Gynecologic cancer treatment: risk factors for therapeutically induced neoplasia

    International Nuclear Information System (INIS)

    Messerschmidt, G.L.; Hoover, R.; Young, R.C.

    1980-01-01

    Therapeutic intervention in a course of illness, while producing the desired result, also may have some adverse long-term effects on the patient. Second malignancies are one of the known complications of therapy. The treatments of gynecologic cancers by surgery, irradiation and chemotherapy have been associated with subsequent neoplasms. The use of normal skin from the thigh to fabricate an artificial vagina has resulted in more squamous cell carcinomas than expected. Alkylating agents used in the treatment of ovarian cancer and other diseases have been shown to lead to an increased risk of leukemia. The incidence of lymphoma and uterine, urinary bladder and colon carcinomas has been associated with prior irradiation for gynecologic disease. The literature regarding the therapeutically induced risk factors in gynecologic therapy is reviewed and areas of our knowledge that require more investigation are identified

  12. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    .2-3.1) for brain cancer, and 3.3 (95% CI, 2.5-4.4) for NHL. Corresponding hazard ratios after childhood leukemia were 10.4 (95% CI, 0.4-223) for thyroid cancer, 7.2 (95% CI, 2.0-26) for brain cancer, and 6.5 (95% CI, 0.4-110) for NHL. Patients with adult leukemia have excess risk of thyroid cancer, brain cancer......Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...

  13. Alcohol consumption and risk of prostate cancer in middle-aged men.

    NARCIS (Netherlands)

    Schoonen, W.M.; Salinas, C.A.; Kiemeney, L.A.L.M.; Stanford, J.L.

    2005-01-01

    Alcohol consumption is a modifiable lifestyle factor that may affect prostate cancer risk. Alcohol alters the hormonal milieu and contains chemical substances such as flavonoids (red wine), which may alter tumor cell growth. Data from a population-based case-control study in King County, WA, were

  14. Risk of cancer in retransplants compared to primary kidney transplants in the United States.

    Science.gov (United States)

    Kalil, Roberto S; Lynch, Charles F; Engels, Eric A

    2015-10-01

    Recipients of kidney transplantation have elevated risk of developing cancer. There are limited data on cancer risk in recipients of kidney retransplantation. We used data from the Transplant Cancer Match Study, which links the U.S. transplant registry with 15 cancer registries. Cancer incidence in recipients of kidney retransplantation and primary kidney transplants was compared utilizing Poisson regression, adjusting for demographic and medical characteristics. We assessed 109 224 primary recipients and 6621 retransplants. Compared to primary recipients, retransplants were younger (median age 40 vs. 46 yr), had higher PRA, and more often received induction with polyclonal antibodies (43% vs. 25%). A total of 5757 cancers were observed in primary recipients and 245 in retransplants. Overall cancer risk was similar in retransplants compared with primary recipients (incidence rate ratio [IRR] 1.06, 95% CI 0.93-1.20, adjusted for age, gender, race/ethnicity, PRA, and use of polyclonal induction). However, renal cell carcinoma (RCC) occurred in excess among retransplants (adjusted IRR 2.03, 95% CI 1.45-2.77), based on 514 cases in primary recipients and 43 cases in retransplants. Overall cancer risk did not differ in retransplants compared to primary recipients. Increased risk of RCC may be explained by the presence of acquired cystic kidney disease, which is more likely to develop with additional time with kidney disease and time spent on dialysis waiting for retransplantation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Intratubular Germ Cell Neoplasia of the Testis, Bilateral Testicular Cancer, and Aberrant Histologies.

    Science.gov (United States)

    Sharma, Pranav; Dhillon, Jasreman; Sexton, Wade J

    2015-08-01

    Intratubular germ cell neoplasia (ITGCN) is a precursor lesion for testicular germ cell tumors, most of which are early stage. ITGCN is also associated with testicular cancer or ITGCN in the contralateral testis, leading to a risk of bilateral testicular malignancy. Testicular biopsy detects most cases, and orchiectomy is the treatment of choice in patients with unilateral ITGCN. Low-dose radiation therapy is recommended in patients with bilateral ITGCN or ITGCN in the solitary testis, but the long-term risks of infertility and hypogonadism need to be discussed with the patient. Rare histologies of primary testicular cancer are also discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Canadian Cancer Risk Management Model: evaluation of cancer control.

    Science.gov (United States)

    Evans, William K; Wolfson, Michael C; Flanagan, William M; Shin, Janey; Goffin, John; Miller, Anthony B; Asakawa, Keiko; Earle, Craig; Mittmann, Nicole; Fairclough, Lee; Oderkirk, Jillian; Finès, Philippe; Gribble, Stephen; Hoch, Jeffrey; Hicks, Chantal; Omariba, D Walter R; Ng, Edward

    2013-04-01

    The aim of this study was to develop a decision support tool to assess the potential benefits and costs of new healthcare interventions. The Canadian Partnership Against Cancer (CPAC) commissioned the development of a Cancer Risk Management Model (CRMM)--a computer microsimulation model that simulates individual lives one at a time, from birth to death, taking account of Canadian demographic and labor force characteristics, risk factor exposures, and health histories. Information from all the simulated lives is combined to produce aggregate measures of health outcomes for the population or for particular subpopulations. The CRMM can project the population health and economic impacts of cancer control programs in Canada and the impacts of major risk factors, cancer prevention, and screening programs and new cancer treatments on population health and costs to the healthcare system. It estimates both the direct costs of medical care, as well as lost earnings and impacts on tax revenues. The lung and colorectal modules are available through the CPAC Web site (www.cancerview.ca/cancerrriskmanagement) to registered users where structured scenarios can be explored for their projected impacts. Advanced users will be able to specify new scenarios or change existing modules by varying input parameters or by accessing open source code. Model development is now being extended to cervical and breast cancers.

  17. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC).

    Science.gov (United States)

    Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Chen, Zhihua; Chen, Ann Y; Permuth-Wey, Jennifer; Aben, Katja Kh; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Sieh, Weiva; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harter, Philipp; Hasmad, Hanis N; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Vierkant, Robert A; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Ian; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Thomsen, Lotte; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Palmieri Weber, Rachel; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Pike, Malcolm C; Poole, Elizabeth M; Schernhammer, Eva; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Amankwah, Ernest; Berchuck, Andrew; Schildkraut, Joellen M; Kelemen, Linda E; Ramus, Susan J; Monteiro, Alvaro N A; Goode, Ellen L; Narod, Steven A; Gayther, Simon A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

    Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10 -4 ]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1 , may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.

  18. Hormonal contraception and risk of cancer

    DEFF Research Database (Denmark)

    Cibula, D.; Gompel, A.; Mueck, A.O.

    2011-01-01

    Fear from increased cancer risk is one of the most significant reasons for low acceptance of reliable contraceptive methods and low compliance.......Fear from increased cancer risk is one of the most significant reasons for low acceptance of reliable contraceptive methods and low compliance....

  19. Hormonal contraception and risk of cancer

    DEFF Research Database (Denmark)

    Cibula, D; Gompel, A; Mueck, A O

    2010-01-01

    Fear from increased cancer risk is one of the most significant reasons for low acceptance of reliable contraceptive methods and low compliance.......Fear from increased cancer risk is one of the most significant reasons for low acceptance of reliable contraceptive methods and low compliance....

  20. Detection of free gastric cancer cell in peripheral and portal blood

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Ho Yoon; Lee, Jong Inn [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    In fact, there is no definite treatment modality after liver or hematogenous metastasis in the gastric cancer. So it is important to develop a new method to predict the high risk patients for systemic recurrence. If we can detect metastatic cell in circulation, it may be beneficial in assessing tumor progression, metastatic potential and prognosis. To establish the RT-PCR methodology for detection of CEA expressing cancer cells in peripheral and portal blood and to define the relationship between peripheral and portal blood detection rate of gastric cancer patients, we performed RT-PCR analysis with peripheral and portal blood samples from 24 patients with gastric cancer (stage Ia,b, n=3; stage II, n=2; stage IIIa, n=9; stage IIIb, n=7; stage IV, n=3) and checked serum CEA level preoperatively. Mean age was 49.2 years old and male : female was 1.2 : 2 (13:11 patients). The mean serum CEA level was 10.4 ng/ml and that was higher than normal in only 2 cases. There was no positive case of tumor cell in portal and peripheral blood using RT-PCR and CEA gene specific primer. Our results indicate that the incidence of circulating cancer cells is unexpectedly very low even in advanced gastric cancer patients. (author). 20 refs.

  1. Detection of free gastric cancer cell in peripheral and portal blood

    International Nuclear Information System (INIS)

    Bang, Ho Yoon; Lee, Jong Inn

    1998-01-01

    In fact, there is no definite treatment modality after liver or hematogenous metastasis in the gastric cancer. So it is important to develop a new method to predict the high risk patients for systemic recurrence. If we can detect metastatic cell in circulation, it may be beneficial in assessing tumor progression, metastatic potential and prognosis. To establish the RT-PCR methodology for detection of CEA expressing cancer cells in peripheral and portal blood and to define the relationship between peripheral and portal blood detection rate of gastric cancer patients, we performed RT-PCR analysis with peripheral and portal blood samples from 24 patients with gastric cancer (stage Ia,b, n=3; stage II, n=2; stage IIIa, n=9; stage IIIb, n=7; stage IV, n=3) and checked serum CEA level preoperatively. Mean age was 49.2 years old and male : female was 1.2 : 2 (13:11 patients). The mean serum CEA level was 10.4 ng/ml and that was higher than normal in only 2 cases. There was no positive case of tumor cell in portal and peripheral blood using RT-PCR and CEA gene specific primer. Our results indicate that the incidence of circulating cancer cells is unexpectedly very low even in advanced gastric cancer patients. (author). 20 refs

  2. Automatic cell cloning assay for determining the clonogenic capacity of cancer and cancer stem-like cells.

    Science.gov (United States)

    Fedr, Radek; Pernicová, Zuzana; Slabáková, Eva; Straková, Nicol; Bouchal, Jan; Grepl, Michal; Kozubík, Alois; Souček, Karel

    2013-05-01

    The clonogenic assay is a well-established in vitro method for testing the survival and proliferative capability of cells. It can be used to determine the cytotoxic effects of various treatments including chemotherapeutics and ionizing radiation. However, this approach can also characterize cells with different phenotypes and biological properties, such as stem cells or cancer stem cells. In this study, we implemented a faster and more precise method for assessing the cloning efficiency of cancer stem-like cells that were characterized and separated using a high-speed cell sorter. Cell plating onto a microplate using an automatic cell deposition unit was performed in a single-cell or dilution rank mode by the fluorescence-activated cell sorting method. We tested the new automatic cell-cloning assay (ACCA) on selected cancer cell lines and compared it with the manual approach. The obtained results were also compared with the results of the limiting dilution assay for different cell lines. We applied the ACCA to analyze the cloning capacity of different subpopulations of prostate and colon cancer cells based on the expression of the characteristic markers of stem (CD44 and CD133) and cancer stem cells (TROP-2, CD49f, and CD44). Our results revealed that the novel ACCA is a straightforward approach for determining the clonogenic capacity of cancer stem-like cells identified in both cell lines and patient samples. Copyright © 2013 International Society for Advancement of Cytometry.

  3. Breast cancer epidemiology and risk factors

    International Nuclear Information System (INIS)

    Broeders, M. J. M.; Verbeek, A. L. M.

    1997-01-01

    Breast cancer is the most common malignancy among women in the Western society. Over the past decades it has become apparent that breast cancer incidence rates are increasing steadily, whereas the mortality rates for breast cancer have remained relatively constant. Information through the media on this rising number of cases has increased breast health awareness but has also introduced anxiety in the female population. This combination of factors has made the need for prevention of breast cancer an urgent matter. Breast cancer does not seem to be a single disease entity. A specific etiologic factor may therefore have more influence on one form may therefore have more influence on one form of breast cancer than another. So far though, as shown in their summary of current knowledge on established and dubious risk factors, no risk factors have been identified that can explain a major part of the incidence. Efforts to identify other ways for primary prevention have also been discouraging, even though breast cancer is one of the most investigated tumours world-wide. Thus, at this point i time, the most important strategy to reduce breast cancer mortality is early detection through individual counselling and organised breast screening programs. The recent isolation of breast cancer susceptibility genes may introduce new ways to reduce the risk of breast cancer in a small subset of women

  4. Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer

    DEFF Research Database (Denmark)

    Graff, Rebecca E; Möller, Sören; Passarelli, Michael N

    2017-01-01

    included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer's risk in twins of affected co-twins relative to the cohort risk (familial risk ratio; FRR). We then estimated the proportion of variation in risk that could be attributed......BACKGROUND & AIMS: We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies. METHODS: Our data set...... to genetic factors (heritability). RESULTS: From earliest registration in 1943 through 2010, 1861 individuals were diagnosed with colon cancer and 1268 with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% CI, 2.4-3.8) relative to the cohort risk. Dizygotic...

  5. Lay Awareness of the Relationship between Age and Cancer Risk.

    Science.gov (United States)

    Taber, Jennifer M; Klein, William M P; Suls, Jerry M; Ferrer, Rebecca A

    2017-04-01

    Cross-sectional studies suggest many people are unaware that cancer risk increases with age, but this misbelief has rarely been studied prospectively, nor are its moderators known. To assess whether people recognize that cancer risk increases with age and whether beliefs differ according to gender, education, smoking status, and family history of cancer. First, items from the cross-sectional Health Information National Trends Survey (n = 2069) were analyzed to examine the association of age and perceived cancer risk. Second, the prospective National Survey of Midlife Development in the United States (n = 3896) was used to assess whether perceived cancer risk changes over a decade. Third, beliefs about the age at which cancer occurs were analyzed using the US Awareness and Beliefs about Cancer survey (n = 1080). As a comparator, perceived risk of heart disease was also examined. Cross-sectionally, older age was associated with lower perceived cancer risk but higher perceived heart disease risk. Prospectively, perceived cancer risk remained stable, whereas perceived heart attack risk increased. Seventy percent of participants reported a belief that cancer is equally likely to affect people of any age. Across three surveys, women and former smokers/smokers who recently quit tended to misunderstand the relationship between age and cancer risk and also expressed relatively higher perceived cancer risk overall. Data from three national surveys indicated that people are unaware that age is a risk factor for cancer. Moreover, those who were least aware perceived the highest risk of cancer regardless of age.

  6. Cancer Stem Cells in Pancreatic Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  7. Cancer Stem Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Karl-Walter Jauch

    2010-08-01

    Full Text Available Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs. Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  8. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  9. Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility.

    Science.gov (United States)

    Sada, Masafumi; Ohuchida, Kenoki; Horioka, Kohei; Okumura, Takashi; Moriyama, Taiki; Miyasaka, Yoshihiro; Ohtsuka, Takao; Mizumoto, Kazuhiro; Oda, Yoshinao; Nakamura, Masafumi

    2016-03-28

    Desmoplasia and hypoxia in pancreatic cancer mutually affect each other and create a tumor-supportive microenvironment. Here, we show that microenvironment remodeling by hypoxic pancreatic stellate cells (PSCs) promotes cancer cell motility through alteration of extracellular matrix (ECM) fiber architecture. Three-dimensional (3-D) matrices derived from PSCs under hypoxia exhibited highly organized parallel-patterned matrix fibers compared with 3-D matrices derived from PSCs under normoxia, and promoted cancer cell motility by inducing directional migration of cancer cells due to the parallel fiber architecture. Microarray analysis revealed that procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in PSCs was the gene that potentially regulates ECM fiber architecture under hypoxia. Stromal PLOD2 expression in surgical specimens of pancreatic cancer was confirmed by immunohistochemistry. RNA interference-mediated knockdown of PLOD2 in PSCs blocked parallel fiber architecture of 3-D matrices, leading to decreased directional migration of cancer cells within the matrices. In conclusion, these findings indicate that hypoxia-induced PLOD2 expression in PSCs creates a permissive microenvironment for migration of cancer cells through architectural regulation of stromal ECM in pancreatic cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Identification of cancer risk and associated behaviour: implications for social marketing campaigns for cancer prevention.

    Science.gov (United States)

    Kippen, Rebecca; James, Erica; Ward, Bernadette; Buykx, Penny; Shamsullah, Ardel; Watson, Wendy; Chapman, Kathy

    2017-08-17

    Community misconception of what causes cancer is an important consideration when devising communication strategies around cancer prevention, while those initiating social marketing campaigns must decide whether to target the general population or to tailor messages for different audiences. This paper investigates the relationships between demographic characteristics, identification of selected cancer risk factors, and associated protective behaviours, to inform audience segmentation for cancer prevention social marketing. Data for this cross-sectional study (n = 3301) are derived from Cancer Council New South Wales' 2013 Cancer Prevention Survey. Descriptive statistics and logistic regression models were used to investigate the relationship between respondent demographic characteristics and identification of each of seven cancer risk factors; demographic characteristics and practice of the seven 'protective' behaviours associated with the seven cancer risk factors; and identification of cancer risk factors and practising the associated protective behaviours, controlling for demographic characteristics. More than 90% of respondents across demographic groups identified sun exposure and smoking cigarettes as moderate or large cancer risk factors. Around 80% identified passive smoking as a moderate/large risk factor, and 40-60% identified being overweight or obese, drinking alcohol, not eating enough vegetables and not eating enough fruit. Women and older respondents were more likely to identify most cancer risk factors as moderate/large, and to practise associated protective behaviours. Education was correlated with identification of smoking as a moderate/large cancer risk factor, and with four of the seven protective behaviours. Location (metropolitan/regional) and country of birth (Australia/other) were weak predictors of identification and of protective behaviours. Identification of a cancer risk factor as moderate/large was a significant predictor for five out

  11. Lactoferricin treatment decreases the rate of cell proliferation of a human colon cancer cell line.

    Science.gov (United States)

    Freiburghaus, C; Janicke, B; Lindmark-Månsson, H; Oredsson, S M; Paulsson, M A

    2009-06-01

    Food components modify the risk of cancer at a large number of sites but the mechanism of action is unknown. In the present investigation, we studied the effect of the peptide lactoferricin derived from bovine milk lactoferrin on human colon cancer CaCo-2 cells. The cells were either untreated or treated with 2.0, 0.2, or 0.02 microM lactoferricin. Cell cycle kinetics were investigated with a bromodeoxyuridine DNA flow cytometric method. The results show that lactoferricin treatment slightly but significantly prolonged the S phase of the cell cycle. Lactoferricin treatment lowered the level of cyclin E1, a protein involved in the regulation of genes required for G(1)/S transition and consequently for efficient S phase progression. The slight prolongation of the S phase resulted in a reduction of cell proliferation, which became more apparent after a long treatment time.

  12. NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis.

    Directory of Open Access Journals (Sweden)

    Yan-fei Liu

    Full Text Available Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2, which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression.

  13. Lung cancer risk of airborne particles for Italian population

    Energy Technology Data Exchange (ETDEWEB)

    Buonanno, G., E-mail: buonanno@unicas.it [Department of Civil and Mechanical Engineering, University of Cassino and Southern Lazio, Via Di Biasio 43, 03043 Cassino, FR (Italy); International Laboratory for Air Quality and Health, Queensland University of Technology, 2 George Street 2, 4001 Brisbane, Qld. (Australia); Giovinco, G., E-mail: giovinco@unicas.it [Department of Civil and Mechanical Engineering, University of Cassino and Southern Lazio, Via Di Biasio 43, 03043 Cassino, FR (Italy); Morawska, L., E-mail: morawska@qut.edu.au [International Laboratory for Air Quality and Health, Queensland University of Technology, 2 George Street 2, 4001 Brisbane, Qld. (Australia); Stabile, L., E-mail: stabile@unicas.it [Department of Civil and Mechanical Engineering, University of Cassino and Southern Lazio, Via Di Biasio 43, 03043 Cassino, FR (Italy)

    2015-10-15

    Airborne particles, including both ultrafine and supermicrometric particles, contain various carcinogens. Exposure and risk-assessment studies regularly use particle mass concentration as dosimetry parameter, therefore neglecting the potential impact of ultrafine particles due to their negligible mass compared to supermicrometric particles. The main purpose of this study was the characterization of lung cancer risk due to exposure to polycyclic aromatic hydrocarbons and some heavy metals associated with particle inhalation by Italian non-smoking people. A risk-assessment scheme, modified from an existing risk model, was applied to estimate the cancer risk contribution from both ultrafine and supermicrometric particles. Exposure assessment was carried out on the basis of particle number distributions measured in 25 smoke-free microenvironments in Italy. The predicted lung cancer risk was then compared to the cancer incidence rate in Italy to assess the number of lung cancer cases attributed to airborne particle inhalation, which represents one of the main causes of lung cancer, apart from smoking. Ultrafine particles are associated with a much higher risk than supermicrometric particles, and the modified risk-assessment scheme provided a more accurate estimate than the conventional scheme. Great attention has to be paid to indoor microenvironments and, in particular, to cooking and eating times, which represent the major contributors to lung cancer incidence in the Italian population. The modified risk assessment scheme can serve as a tool for assessing environmental quality, as well as setting up exposure standards for particulate matter. - Highlights: • Lung cancer risk for non-smoking Italian population due to particle inhalation. • The average lung cancer risk for Italian population is equal to 1.90×10{sup −2}. • Ultrafine particle is the aerosol metric mostly contributing to lung cancer risk. • B(a)P is the main (particle-bounded) compound

  14. Lung cancer risk of airborne particles for Italian population

    International Nuclear Information System (INIS)

    Buonanno, G.; Giovinco, G.; Morawska, L.; Stabile, L.

    2015-01-01

    Airborne particles, including both ultrafine and supermicrometric particles, contain various carcinogens. Exposure and risk-assessment studies regularly use particle mass concentration as dosimetry parameter, therefore neglecting the potential impact of ultrafine particles due to their negligible mass compared to supermicrometric particles. The main purpose of this study was the characterization of lung cancer risk due to exposure to polycyclic aromatic hydrocarbons and some heavy metals associated with particle inhalation by Italian non-smoking people. A risk-assessment scheme, modified from an existing risk model, was applied to estimate the cancer risk contribution from both ultrafine and supermicrometric particles. Exposure assessment was carried out on the basis of particle number distributions measured in 25 smoke-free microenvironments in Italy. The predicted lung cancer risk was then compared to the cancer incidence rate in Italy to assess the number of lung cancer cases attributed to airborne particle inhalation, which represents one of the main causes of lung cancer, apart from smoking. Ultrafine particles are associated with a much higher risk than supermicrometric particles, and the modified risk-assessment scheme provided a more accurate estimate than the conventional scheme. Great attention has to be paid to indoor microenvironments and, in particular, to cooking and eating times, which represent the major contributors to lung cancer incidence in the Italian population. The modified risk assessment scheme can serve as a tool for assessing environmental quality, as well as setting up exposure standards for particulate matter. - Highlights: • Lung cancer risk for non-smoking Italian population due to particle inhalation. • The average lung cancer risk for Italian population is equal to 1.90×10 −2 . • Ultrafine particle is the aerosol metric mostly contributing to lung cancer risk. • B(a)P is the main (particle-bounded) compound contributing

  15. Epidemiologic review of marijuana use and cancer risk.

    Science.gov (United States)

    Hashibe, Mia; Straif, Kurt; Tashkin, Donald P; Morgenstern, Hal; Greenland, Sander; Zhang, Zuo-Feng

    2005-04-01

    Marijuana is the most commonly used illegal drug in the United States and is considered by young adults to be the illicit drug with the least risk. On the other hand, marijuana smoke contains several of the same carcinogens and co-carcinogens as the tar from tobacco, raising concerns that smoking of marijuana may be a risk factor for tobacco-related cancers. We reviewed two cohort studies and 14 case-control studies with assessment of the association of marijuana use and cancer risk. In the cohort studies, increased risks of lung or colorectal cancer due to marijuana smoking were not observed, but increased risks of prostate and cervical cancers among non-tobacco smokers, as well as adult-onset glioma among tobacco and non-tobacco smokers, were observed. The 14 case-control studies included four studies on head and neck cancers, two studies on lung cancer, two studies on non-Hodgkin's lymphoma, one study on anal cancer, one study on penile cancer, and four studies on childhood cancers with assessment of parental exposures. Zhang and colleagues reported that marijuana use may increase risk of head and neck cancers in a hospital-based case-control study in the United States, with dose-response relations for both frequency and duration of use. However, Rosenblatt and co-workers reported no association between oral cancer and marijuana use in a population-based case-control study. An eightfold increase in risk among marijuana users was observed in a lung cancer study in Tunisia. However, there was no assessment of the dose response, and marijuana may have been mixed with tobacco. Parental marijuana use during gestation was associated with increased risks of childhood leukemia, astrocytoma, and rhabdomyosarcoma, but dose-response relations were not assessed. In summary, sufficient studies are not available to adequately evaluate marijuana impact on cancer risk. Several limitations of previous studies include possible underreporting where marijuana use is illegal, small

  16. Mitochondrial dysfunction and risk of cancer

    DEFF Research Database (Denmark)

    Lund, M; Melbye, M; Diaz, L J

    2015-01-01

    matrilineal relatives to a cohort member with a genetically confirmed maternally inherited mDNA mutation. Information on cancer was obtained by linkage to the Danish Cancer Register. Standardised incidence ratios (SIRs) were used to assess the relative risk of cancer. RESULTS: During 7334 person......-years of follow-up, 19 subjects developed a primary cancer. The corresponding SIR for any primary cancer was 1.06 (95% confidence interval 0.68-1.63). Subgroup analyses according to mutational subtype yielded similar results, for example, a SIR of 0.94 (95% CI 0.53 to 1.67) for the m.3243A>G maternally inherited...... mDNA mutation, cases=13. CONCLUSIONS: Patients with mitochondrial dysfunction do not appear to be at increased risk of cancer compared with the general population....

  17. Screening for breast cancer in a high-risk series

    International Nuclear Information System (INIS)

    Woodard, E.D.; Hempelmann, L.H.; Janus, J.; Logan, W.; Dean, P.

    1982-01-01

    A unique cohort of women at increased risk of breast cancer because of prior X-ray treatment of acute mastitis and their selected high-risk siblings were offered periodic breast cancer screening including physical examination of the breasts, mammography, and thermography. Twelve breast cancers were detected when fewer than four would have been expected based on age-specific breast cancer detection rates from the National Cancer institute/American Cancer Society Breast Cancer Demonstration Detection Projects. Mammograpy was positive in all cases but physical examination was positive in only three cases. Thermography was an unreliable indicator of disease. Given the concern over radiation-induced risk, use of low-dose technique and of criteria for participation that select women at high risk of breast cancer will maximize the benefit/risk ratio for mammography screening

  18. Inactivated Sendai virus particle upregulates cancer cell expression of intercellular adhesion molecule-1 and enhances natural killer cell sensitivity on cancer cells.

    Science.gov (United States)

    Li, Simin; Nishikawa, Tomoyuki; Kaneda, Yasufumi

    2017-12-01

    We have already reported that the inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) has multiple anticancer effects, including induction of cancer-selective cell death and activation of anticancer immunity. The HVJ-E stimulates dendritic cells to produce cytokines and chemokines such as β-interferon, interleukin-6, chemokine (C-C motif) ligand 5, and chemokine (C-X-C motif) ligand 10, which activate both CD8 + T cells and natural killer (NK) cells and recruit them to the tumor microenvironment. However, the effect of HVJ-E on modulating the sensitivity of cancer cells to immune cell attack has yet to be investigated. In this study, we found that HVJ-E induced the production of intercellular adhesion molecule-1 (ICAM-1, CD54), a ligand of lymphocyte function-associated antigen 1, in several cancer cell lines through the activation of nuclear factor-κB downstream of retinoic acid-inducible gene I and the mitochondrial antiviral signaling pathway. The upregulation of ICAM-1 on the surface of cancer cells increased the sensitivity of cancer cells to NK cells. Knocking out expression of ICAM-1 in MDA-MB-231 cells using the CRISPR/Cas9 method significantly reduced the killing effect of NK cells on ICAM-1-depleted MDA-MB-231 cells. In addition, HVJ-E suppressed tumor growth in MDA-MB-231 tumor-bearing SCID mice, and the HVJ-E antitumor effect was impaired when NK cells were depleted by treatment with the anti-asialo GM1 antibody. Our findings suggest that HVJ-E enhances NK cell sensitivity against cancer cells by increasing ICAM-1 expression on the cancer cell surface. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  19. Hot Food and Beverage Consumption and the Risk of Esophageal Cancer: A Meta-Analysis.

    Science.gov (United States)

    Andrici, Juliana; Eslick, Guy D

    2015-12-01

    Esophageal cancer is a neoplasm with a poor prognosis. Its two histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have been associated with different risk factors. The possibility of an association between the consumption of hot food and beverages and esophageal cancer, especially ESCC, has long been suspected, presenting a potentially modifiable risk factor. A meta-analysis of existing observational studies was performed to provide a quantitative estimate of the risk of esophageal cancer associated with the consumption of hot food and drink. A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to November 11, 2014. Pooled ORs and 95% CIs were calculated using a random effects model for the risk of esophageal cancer associated with the consumption of hot food and drink. Subgroup analyses were conducted for ESCC and EAC, as well as for studies that adjusted for tobacco smoking and alcohol consumption, two well-recognized risk factors for ESCC. Consumption of hot food and drink was associated with an increased risk of any esophageal cancer (OR=1.90, 95% CI=1.46, 2.48). Heterogeneity was observed. There was an increased risk of ESCC (OR=2.29, 95% CI=1.79, 2.93), which remained even after adjusting for significant confounding variables (OR=2.39, 95% CI=1.71, 3.33). The relationship was not significant for EAC. The consumption of hot food and beverages was associated with an increased risk of esophageal cancer, particularly ESCC. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  20. Targetless T cells in cancer immunotherapy

    DEFF Research Database (Denmark)

    thor Straten, Eivind Per; Garrido, Federico

    2016-01-01

    Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell...... infiltrate tumor tissues and destroy HLA class I positive tumor cells expressing the specific antigen. In fact, current progress in the field of cancer immune therapy is based on the capacity of T cells to kill cancer cells that present tumor antigen in the context on an HLA class I molecule. However......, it is also well established that cancer cells are often characterized by loss or down regulation of HLA class I molecules, documented in a variety of human tumors. Consequently, immune therapy building on CD8 T cells will be futile in patients harboring HLA class-I negative or deficient cancer cells...

  1. Testicular germ cell cancer incidence in an immigration perspective, Denmark, 1978 to 2003

    DEFF Research Database (Denmark)

    Schmiedel, Sven; Schüz, Joachim; Skakkebaek, Niels E

    2010-01-01

    The incidence rate of testicular germ cell cancer in Denmark increased up to the 1990s to become among the highest in the world. Since recently rate stabilization was suggested, we determined whether it is due to an increasing number of immigrants at lower risk for this cancer....

  2. Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

    Science.gov (United States)

    Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

    2017-08-02

    The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

  3. Diabetes as a risk factor to cancer: Functional role of fermented papaya preparation as phytonutraceutical adjunct in the treatment of diabetes and cancer

    International Nuclear Information System (INIS)

    Aruoma, Okezie I.; Somanah, Jhoti; Bourdon, Emmanuel; Rondeau, Philippe; Bahorun, Theeshan

    2014-01-01

    Highlights: • Cancer incidence and mortality is linked to hyperglycemia and some anti-diabetes drugs. • FPP is a safe nutraceutical adjunct for augmenting therapeutic regimens in diabetes and cancer management. • FPP through its hypoglycemic and antioxidant sensing may impact and mitigate the side effects of anticancer drugs. • FPP can diminish the intensity of side effects associated with acute radiation therapy. • FPP can maintain the integrity of erythrocyte during cancer chemotherapy augmenting compliance of treatment. - Abstract: Oncologists and diabetologists quote scientific data from epidemiological and in vitro studies to show that high levels of insulin and glucose, in combination with oxidative stress and chronic inflammation, can heighten the risk of developing cancer amongst patients with diabetes. Although the cancers that have been consistently associated with type 2 diabetes include pancreatic, colorectal, breast and liver cancer, the preponderance of the disease risk factors such as obesity, inflammation, hyperglycemia, hyperinsulinaemia (as a result of insulin resistance and oxidative β-cell damage) and the indirect influence of anti-diabetic medications are increasingly being defined. Fermented papaya preparation (FPP) has defined antioxidant and immune-modulating potentials. The ability of FPP influence signaling cascades associated with cell growth and survival presents a rational for chemopreventive adjunct that can be used in combination with traditional redox based therapies that target oxidative stress in the cancer micro environment. It is further suggested that the demonstrated efficacy FPP to control blood glucose, excessive inflammation and modulate free radical-induced oxidative damage which are triggers of liver, bladder, breast and prostate cancers in type 2 diabetics, may favorably mitigate the side effects of ensuing diabetes and cancer therapy. What remains paramount is early cancer detection and early determination of

  4. Diabetes as a risk factor to cancer: Functional role of fermented papaya preparation as phytonutraceutical adjunct in the treatment of diabetes and cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aruoma, Okezie I., E-mail: oaruoma@auhs.edu [Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA (United States); Somanah, Jhoti [ANDI Center for Biomedical and Biomaterials Research, University of Mauritius, MSIRI Building, Réduit (Mauritius); Bourdon, Emmanuel; Rondeau, Philippe [Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO), Université de La Réunion, Plateforme CYROI, Saint Denis (France); Bahorun, Theeshan, E-mail: tbahorun@uom.ac.mu [ANDI Center for Biomedical and Biomaterials Research, University of Mauritius, MSIRI Building, Réduit (Mauritius)

    2014-10-15

    Highlights: • Cancer incidence and mortality is linked to hyperglycemia and some anti-diabetes drugs. • FPP is a safe nutraceutical adjunct for augmenting therapeutic regimens in diabetes and cancer management. • FPP through its hypoglycemic and antioxidant sensing may impact and mitigate the side effects of anticancer drugs. • FPP can diminish the intensity of side effects associated with acute radiation therapy. • FPP can maintain the integrity of erythrocyte during cancer chemotherapy augmenting compliance of treatment. - Abstract: Oncologists and diabetologists quote scientific data from epidemiological and in vitro studies to show that high levels of insulin and glucose, in combination with oxidative stress and chronic inflammation, can heighten the risk of developing cancer amongst patients with diabetes. Although the cancers that have been consistently associated with type 2 diabetes include pancreatic, colorectal, breast and liver cancer, the preponderance of the disease risk factors such as obesity, inflammation, hyperglycemia, hyperinsulinaemia (as a result of insulin resistance and oxidative β-cell damage) and the indirect influence of anti-diabetic medications are increasingly being defined. Fermented papaya preparation (FPP) has defined antioxidant and immune-modulating potentials. The ability of FPP influence signaling cascades associated with cell growth and survival presents a rational for chemopreventive adjunct that can be used in combination with traditional redox based therapies that target oxidative stress in the cancer micro environment. It is further suggested that the demonstrated efficacy FPP to control blood glucose, excessive inflammation and modulate free radical-induced oxidative damage which are triggers of liver, bladder, breast and prostate cancers in type 2 diabetics, may favorably mitigate the side effects of ensuing diabetes and cancer therapy. What remains paramount is early cancer detection and early determination of

  5. Human Papilloma Virus in Head and Neck Squamous Cell Cancer

    Science.gov (United States)

    Asvadi Kermani, I; Seifi, SH; Dolatkhah, R; Sakhinia, E; Dastgiri, S; Ebrahimi, A; Lotfy, A; Esmaeili, HA; G, Mohammadi; M, Naderpour; SH, Hajalipour; Haggi A, Asghari; M, Nadri

    2012-01-01

    Background Epidemiologic and molecular evidences have established a strong link between high risk types of Human Papilloma Virus and a subgroup of Head and Neck Squamous Cell Carcinomas (HNSCC). We evaluated the frequency of HPV positivity in HNSCC and its relationship to demographic and some risk factor variables in an open case- control study. Methods Fourteen recently diagnosed patients with squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin-embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94 control cancer-free subjects were collected for DNA analysis. Multivariable logistic regression method was used to calculate odds ratio for case-control comparisons. Results High risk HPV was detected in 6(42.8%) patients, and 6(5.3%) control subjects which was statistically significant (p<0.0001). HPV-18 was the most frequent type both in the cases and controls. HPV-16 DNA was detected in two patients of the case group, but it was not detected in any of the controls. The relation between demographic and risk factor variables was not statistically significant. Conclusion HPV infection has a significant impact on HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant degeneration in such cancers amongst some communities. It is vital to introduce and conduct immunization schedules in health care systems to protect communities to some extent. PMID:25780535

  6. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2016-12-01

    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  7. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Cancer stem cells (CSCs), a cell population with acquired perpetuating self-renewal properties which

  8. Risk perception after genetic counseling in patients with increased risk of cancer

    Directory of Open Access Journals (Sweden)

    Rantala Johanna

    2009-08-01

    Full Text Available Abstract Background Counselees are more aware of genetics and seek information, reassurance, screening and genetic testing. Risk counseling is a key component of genetic counseling process helping patients to achieve a realistic view for their own personal risk and therefore adapt to the medical, psychological and familial implications of disease and to encourage the patient to make informed choices 12. The aim of this study was to conceptualize risk perception and anxiety about cancer in individuals attending to genetic counseling. Methods The questionnaire study measured risk perception and anxiety about cancer at three time points: before and one week after initial genetic counseling and one year after completed genetic investigations. Eligibility criteria were designed to include only index patients without a previous genetic consultation in the family. A total of 215 individuals were included. Data was collected during three years period. Results Before genetic counseling all of the unaffected participants subjectively estimated their risk as higher than their objective risk. Participants with a similar risk as the population overestimated their risk most. All risk groups estimated the risk for children's/siblings to be lower than their own. The benefits of preventive surveillance program were well understood among unaffected participants. The difference in subjective risk perception before and directly after genetic counseling was statistically significantly lower in all risk groups. Difference in risk perception for children as well as for population was also statistically significant. Experienced anxiety about developing cancer in the unaffected subjects was lower after genetic counseling compared to baseline in all groups. Anxiety about cancer had clear correlation to perceived risk of cancer before and one year after genetic investigations. The affected participants overestimated their children's risk as well as risk for anyone in

  9. Advanced research on separating prostate cancer stem cells

    International Nuclear Information System (INIS)

    Hao Yumei; He Xin; Song Naling

    2013-01-01

    Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

  10. Development and prospective validation of a model estimating risk of readmission in cancer patients.

    Science.gov (United States)

    Schmidt, Carl R; Hefner, Jennifer; McAlearney, Ann S; Graham, Lisa; Johnson, Kristen; Moffatt-Bruce, Susan; Huerta, Timothy; Pawlik, Timothy M; White, Susan

    2018-02-26

    Hospital readmissions among cancer patients are common. While several models estimating readmission risk exist, models specific for cancer patients are lacking. A logistic regression model estimating risk of unplanned 30-day readmission was developed using inpatient admission data from a 2-year period (n = 18 782) at a tertiary cancer hospital. Readmission risk estimates derived from the model were then calculated prospectively over a 10-month period (n = 8616 admissions) and compared with actual incidence of readmission. There were 2478 (13.2%) unplanned readmissions. Model factors associated with readmission included: emergency department visit within 30 days, >1 admission within 60 days, non-surgical admission, solid malignancy, gastrointestinal cancer, emergency admission, length of stay >5 days, abnormal sodium, hemoglobin, or white blood cell count. The c-statistic for the model was 0.70. During the 10-month prospective evaluation, estimates of readmission from the model were associated with higher actual readmission incidence from 20.7% for the highest risk category to 9.6% for the lowest. An unplanned readmission risk model developed specifically for cancer patients performs well when validated prospectively. The specificity of the model for cancer patients, EMR incorporation, and prospective validation justify use of the model in future studies designed to reduce and prevent readmissions. © 2018 Wiley Periodicals, Inc.

  11. Anthropometric characteristics and ovarian cancer risk and survival.

    Science.gov (United States)

    Minlikeeva, Albina N; Moysich, Kirsten B; Mayor, Paul C; Etter, John L; Cannioto, Rikki A; Ness, Roberta B; Starbuck, Kristen; Edwards, Robert P; Segal, Brahm H; Lele, Sashikant; Odunsi, Kunle; Diergaarde, Brenda; Modugno, Francesmary

    2018-02-01

    Multiple studies have examined the role of anthropometric characteristics in ovarian cancer risk and survival; however, their results have been conflicting. We investigated the associations between weight change, height and height change and risk and outcome of ovarian cancer using data from a large population-based case-control study. Data from 699 ovarian cancer cases and 1,802 controls who participated in the HOPE study were included. We used unconditional logistic regression adjusted for age, race, number of pregnancies, use of oral contraceptives, and family history of breast or ovarian cancer to examine the associations between self-reported height and weight and height change with ovarian cancer risk. Cox proportional hazards regression models adjusted for age and stage were used to examine the association between the exposure variables and overall and progression-free survival among ovarian cancer cases. We observed an increased risk of ovarian cancer mortality and progression for gaining more than 20 pounds between ages 18-30, HR 1.36; 95% CI 1.05-1.76, and HR 1.31; 95% CI 1.04-1.66, respectively. Losing weight and gaining it back multiple times was inversely associated with both ovarian cancer risk, OR 0.78; 95% CI 0.63-0.97 for 1-4 times and OR 0.73; 95% CI 0.54-0.99 for 5-9 times, and mortality, HR 0.63; 95% CI 0.40-0.99 for 10-14 times. Finally, being taller during adolescence and adulthood was associated with increased risk of mortality. Taller stature and weight gain over lifetime were not related to ovarian cancer risk. Our results suggest that height and weight and their change over time may influence ovarian cancer risk and survival. These findings suggest that biological mechanisms underlying these associations may be hormone driven and may play an important role in relation to ovarian carcinogenesis and tumor progression.

  12. Stereotactic body radiotherapy for renal cell cancer and pancreatic cancer. Literature review and practice recommendations of the DEGRO Working Group on Stereotactic Radiotherapy

    International Nuclear Information System (INIS)

    Panje, Cedric; Andratschke, Nikolaus; Guckenberger, Matthias; Brunner, Thomas B.; Niyazi, Maximilian

    2016-01-01

    This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a literature review and practice recommendations for stereotactic body radiotherapy (SBRT) of primary renal cell cancer and primary pancreatic cancer. A literature search on SBRT for both renal cancer and pancreatic cancer was performed with focus on prospective trials and technical aspects for clinical implementation. Data on renal and pancreatic SBRT are limited, but show promising rates of local control for both treatment sites. For pancreatic cancer, fractionated SBRT should be preferred to single-dose treatment to reduce the risk of gastrointestinal toxicity. Motion-compensation strategies and image guidance are paramount for safe SBRT delivery in both tumor entities. SBRT for renal cancer and pancreatic cancer have been successfully evaluated in phase I and phase II trials. Pancreatic SBRT should be practiced carefully and only within prospective protocols due to the risk of severe gastrointestinal toxicity. SBRT for primary renal cell cancer appears a viable option for medically inoperable patients but future research needs to better define patient selection criteria and the detailed practice of SBRT. (orig.) [de

  13. Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell Carcinoma.

    Science.gov (United States)

    Dusingize, Jean Claude; Olsen, Catherine M; Pandeya, Nirmala P; Subramaniam, Padmini; Thompson, Bridie S; Neale, Rachel E; Green, Adèle C; Whiteman, David C

    2017-08-01

    Sunlight is the principal environmental risk factor for keratinocyte cancers, but other carcinogens have also been implicated, including tobacco smoke. Findings have been conflicting, however. We investigated associations between cigarette smoking and incidence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in QSkin, a prospective study of skin cancer (N = 43,794). Smoking history was self-reported at baseline; newly diagnosed BCCs and SCCs were ascertained through data linkage and verified by histopathology reports. We restricted analyses to white participants who at baseline reported no past history of skin cancer excisions and no more than five destructively treated actinic skin lesions. We fitted Cox proportional hazards models, adjusted for known confounders. Compared with never smokers, current smokers had significantly lower risks of BCC (hazard ratio = 0.6; 95% confidence interval = 0.4-0.9) but significantly higher risks of SCC (hazard ratio = 2.3; 95% confidence interval = 1.5-3.6). Former smokers had similar risks for BCC and SCC as never smokers. Among smokers, we observed no dose-response trends with duration of smoking, intensity, or time since quitting. On further analysis, current smokers had fewer skin examinations and procedures than never smokers, suggesting greater opportunities for detection among never smokers. Strengths include large sample size, prospective design, and virtually complete follow-up; however, histologic details were missing for a proportion of excised tumors. In conclusion, current smokers had a lower incidence of BCC (possibly because of detection bias) but higher rates of SCC. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Clinical Trial Design for Testing the Stem Cell Model for the Prevention and Treatment of Cancer

    International Nuclear Information System (INIS)

    Reddy, Rishindra M.; Kakarala, Madhuri; Wicha, Max S.

    2011-01-01

    The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples

  15. Clinical Trial Design for Testing the Stem Cell Model for the Prevention and Treatment of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Rishindra M., E-mail: reddyrm@med.umich.edu [Medical Center, University of Michigan, 1500 E. Medical Center Drive, 2120 Taubman Center, Ann Arbor, MI 48109 (United States); Kakarala, Madhuri; Wicha, Max S. [Comprehensive Cancer Center, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109 (United States)

    2011-06-20

    The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples.

  16. Long working hours and cancer risk: a multi-cohort study.

    Science.gov (United States)

    Heikkila, Katriina; Nyberg, Solja T; Madsen, Ida E H; de Vroome, Ernest; Alfredsson, Lars; Bjorner, Jacob J; Borritz, Marianne; Burr, Hermann; Erbel, Raimund; Ferrie, Jane E; Fransson, Eleonor I; Geuskens, Goedele A; Hooftman, Wendela E; Houtman, Irene L; Jöckel, Karl-Heinz; Knutsson, Anders; Koskenvuo, Markku; Lunau, Thorsten; Nielsen, Martin L; Nordin, Maria; Oksanen, Tuula; Pejtersen, Jan H; Pentti, Jaana; Shipley, Martin J; Steptoe, Andrew; Suominen, Sakari B; Theorell, Töres; Vahtera, Jussi; Westerholm, Peter J M; Westerlund, Hugo; Dragano, Nico; Rugulies, Reiner; Kawachi, Ichiro; Batty, G David; Singh-Manoux, Archana; Virtanen, Marianna; Kivimäki, Mika

    2016-03-29

    Working longer than the maximum recommended hours is associated with an increased risk of cardiovascular disease, but the relationship of excess working hours with incident cancer is unclear. This multi-cohort study examined the association between working hours and cancer risk in 116 462 men and women who were free of cancer at baseline. Incident cancers were ascertained from national cancer, hospitalisation and death registers; weekly working hours were self-reported. During median follow-up of 10.8 years, 4371 participants developed cancer (n colorectal cancer: 393; n lung cancer: 247; n breast cancer: 833; and n prostate cancer: 534). We found no clear evidence for an association between working hours and the overall cancer risk. Working hours were also unrelated the risk of incident colorectal, lung or prostate cancers. Working ⩾55 h per week was associated with 1.60-fold (95% confidence interval 1.12-2.29) increase in female breast cancer risk independently of age, socioeconomic position, shift- and night-time work and lifestyle factors, but this observation may have been influenced by residual confounding from parity. Our findings suggest that working long hours is unrelated to the overall cancer risk or the risk of lung, colorectal or prostate cancers. The observed association with breast cancer would warrant further research.

  17. The cancer-germline antigen SSX2 causes cell cycle arrest and DNA damage in cancer cells

    DEFF Research Database (Denmark)

    Greve, Katrine Buch Vidén; Lindgreen, Jonas; Terp, Mikkel Green

    2011-01-01

    The SSX family of cancer and germline antigens is mainly expressed in the germ cells of healthy individuals as well as wide range of cancers and is therefore potential targets for immunotherapy. However, little is known about the role of SSX proteins in tumorigenesis and normal cell function. Here......, we show that SSX2 is involved in regulation of cancer cell growth. We found that ectopic expression of SSX2 in melanoma and colon cancer cells strongly reduced cell growth and induced apoptosis in vitro. Importantly, in a xenograft mouse model, the growth of tumors derived from SSX2 overexpressing...... melanoma cells was severely reduced compared to those derived from the isogenic parental cell line. Cell cycle analysis showed that SSX2 caused an accumulation of cells arrested in G1. Consistent with this, we observed a marked decrease in cells expressing the proliferation marker Ki67 and concomitantly...

  18. ABO blood group and risk of cancer

    DEFF Research Database (Denmark)

    Vasan, Senthil K; Hwang, Jinseub; Rostgaard, Klaus

    2016-01-01

    groups and site-specific cancer risk in a large cohort of healthy blood donors from Sweden and Denmark. RESULTS: A total of 1.6 million donors were followed over 27 million person-years (20 million in Sweden and 7 million in Denmark). We observed 119,584 cancer cases. Blood groups A, AB and B were......INTRODUCTION: The associations between ABO blood group and cancer risk have been studied repeatedly, but results have been variable. Consistent associations have only been reported for pancreatic and gastric cancers. MATERIALS AND METHODS: We estimated associations between different ABO blood...... associated either with increased or decreased risk of cancer at 13 anatomical sites (p≤0.05), compared to blood group O. Consistent with assessment using a false discovery rate approach, significant associations with ABO blood group were observed for cancer of the pancreas, breast, and upper gastrointestinal...

  19. Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure.

    Science.gov (United States)

    Karagas, Margaret R; Nelson, Heather H; Zens, Michael S; Linet, Martha; Stukel, Therese A; Spencer, Steve; Applebaum, Katie M; Mott, Leila; Mabuchi, Kiyohiko

    2007-11-01

    Epidemiologic studies consistently find enhanced risk of basal cell carcinoma of the skin among individuals exposed to ionizing radiation, but it is unclear whether the radiation effect occurs for squamous cell carcinoma. It is also not known whether subgroups of individuals are at greater risk, eg, those with radiation sensitivity or high ultraviolet radiation exposure. We analyzed data from a case-control study of keratinocyte cancers in New Hampshire. Incident cases diagnosed in 1993-1995 and 1997-2000 were identified through a state-wide skin cancer surveillance system, and controls were identified through the Department of Transportation and Center for Medicare and Medicaid Service Files (n = 1121 basal cell carcinoma cases, 854 squamous cell carcinoma cases, and 1049 controls). We found an association between history of radiation treatment and basal cell carcinoma. The association was especially strong for basal cell carcinomas arising within the radiation treatment field (odds ratio = 2.6; 95% confidence interval = 1.5-4.3), and among those treated with radiation therapy before age 20 (3.4; 1.8-6.4), those whose basal cell carcinomas occurred 40 or more years after radiation treatment (3.2; 1.8-5.8), and those treated with radiation for acne (11; 2.7-49). Similar age and time patterns of risk were observed for squamous cell carcinoma, although generally with smaller odds ratios. For basal cell carcinoma, early exposure to radiation treatment was a risk factor largely among those without a history of severe sunburns, whereas for squamous cell carcinoma, radiation treatment was a risk factor primarily among those with a sun-sensitive skin type (ie, a tendency to sunburn). Radiation treatment, particularly if experienced before age 20, seems to increase the long-term risk of both basal and squamous cell carcinomas of the skin. These risks may differ by sun exposure or host response to sunlight exposure.

  20. Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

    Science.gov (United States)

    Olivan, M.; Rigau, M.; Colás, E.; Garcia, M.; Montes, M.; Sequeiros, T.; Regis, L.; Celma, A.; Planas, J.; Placer, J.; Reventós, J.; de Torres, I.; Doll, A.; Morote, J.

    2015-01-01

    Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812), P < 0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155), P = 0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939), P < 0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence. PMID:25649906

  1. The LKB1 tumor suppressor differentially affects anchorage independent growth of HPV positive cervical cancer cell lines

    International Nuclear Information System (INIS)

    Mack, Hildegard I.D.; Munger, Karl

    2013-01-01

    Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown. Based on a previous study that reported an association between liver kinase B1 (LKB1) tumor suppressor loss and poor outcome in cervical cancer, we sought to determine the molecular basis for this observation. LKB1-negative cervical and lung cancer cells were reconstituted with wild type or kinase defective LKB1 mutants and we examined the importance of LKB1 catalytic activity in known LKB1-regulated processes including inhibition of cell proliferation and elevated resistance to energy stress. Our studies revealed marked differences in the biological activities of two kinase defective LKB1 mutants in the various cell lines. Thus, our results suggest that LKB1 may be a cell-type specific tumor suppressor. - Highlights: • LKB1 is a tumor suppressor that is linked to Peutz-Jeghers syndrome. • Peutz-Jeghers syndrome patients have a high incidence of cervical cancer. • Cervical cancer is caused by HPV infections. • This study investigates LKB1 tumor suppressor activity in cervical cancer

  2. Risk-optimized proton therapy to minimize radiogenic second cancers

    DEFF Research Database (Denmark)

    Rechner, Laura A; Eley, John G; Howell, Rebecca M

    2015-01-01

    Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were...... to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment...

  3. Association between allergies and risk of pancreatic cancer.

    Science.gov (United States)

    Cotterchio, Michelle; Lowcock, Elizabeth; Hudson, Thomas J; Greenwood, Celia; Gallinger, Steven

    2014-03-01

    Less than 10% of pancreatic cancer cases survive 5 years, yet its etiology is not well understood. Studies suggest allergies are associated with reduced pancreatic cancer risk. Our study collected additional information on allergies (including skin prick test results and differentiation of allergic/nonallergic asthma), and is the first to assess possible confounding by allergy medications. A population-based case-control study was designed to comprehensively assess the association between allergy and pancreatic cancer risk. Pancreas cancer cases were diagnosed during 2011 to 2012, and identified through the Ontario Cancer Registry (345 cases). Population-based controls were identified using random digit dialing and age/sex frequency matched to cases (1,285 controls). Questionnaires collected lifetime allergy history (type of allergy, age at onset, skin prick testing results), allergy medications, and established pancreas cancer risk factors. Logistic regression was used to estimate odd ratios and test potential confounders, including allergy medications. Hay fever was associated with a significant reduction in pancreatic cancer risk [AOR = 0.68; 95% confidence intervals (CI), 0.52-0.89], and reduction was greatest for those whose skin prick test was positive for hay fever allergens. No particular patterns were observed as regards age at onset and duration of allergy. Positive dust/mold allergy skin prick test and animal allergies were associated with a statistically significant reduced pancreatic cancer risk; AOR = 0.49; 95% CI, 0.31-0.78 and AOR = 0.68; 95% CI, 0.46-0.99, respectively. Asthma was not associated with pancreatic cancer risk. These findings support the growing body of evidence that suggests certain allergies are associated with reduced pancreatic cancer risk. ©2014 AACR.

  4. Molecular imaging of hypoxia in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Yip, Connie; Blower, Philip J.; Goh, Vicky; Landau, David B.; Cook, Gary J.R.

    2015-01-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  5. Molecular imaging of hypoxia in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Connie [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); St Thomas' Hospital, Imaging 2, London (United Kingdom); Blower, Philip J. [King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Goh, Vicky [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Clinical Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J.R. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Clinical PET Imaging Centre, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2015-05-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  6. Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth

    Science.gov (United States)

    Kim, EuiJoo

    2017-01-01

    Introduction The regulation of reactive oxygen species (ROS) exists as a therapeutic target for cancer treatments. Previous studies have shown that ursodeoxycholic acid (UDCA) suppresses the proliferation of colon cancer cells. The aim of this study was to evaluate the effect of UDCA upon the proliferation of colon cancer cells as a direct result of the regulation of ROS. Method Colon cancer cell lines (HT29 and HCT116) were treated with UDCA. The total number of cells and the number of dead cells were determined using cell counters. A fluorescein isothiocyanate-bromodeoxyuridine flow kit was used to analyze cell cycle variations. Upon exposure to UDCA, the protein levels of p27, p21, CDK2, CDK4 and CDK6 were determined using western blotting, and qRT-PCR was used to determine levels of mRNA. We preformed dichlorofluorescindiacetate (DCF-DA) staining to detect alteration of intracellular ROS using fluorescence activated cell sorting (FACS). Colon cancer stem-like cell lines were generated by tumorsphere culture and treated with UDCA for seven days. The total number of tumorspheres was determined using microscopy. Results We found that UDCA reduced the total number of colon cancer cells, but did not increase the number of dead cells. UDCA inhibited the G1/S and G2/M transition phases in colon cancer cells. UDCA induced expression of cell cycle inhibitors such as p27 and p21. However, it was determined that UDCA suppressed levels of CDK2, CDK4, and CDK6. UDCA regulated intracellular ROS generation in colon cancer cells, and induced activation of Erk1/2. Finally, UDCA inhibited formation of colon cancer stem-like cells. Conclusion Our results indicate that UDCA suppresses proliferation through regulation of oxidative stress in colon cancer cells, as well as colon cancer stem-like cells. PMID:28708871

  7. Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

    Science.gov (United States)

    Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

    2017-01-01

    There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Risks of CIN 2+, CIN 3+, and Cancer by Cytology and Human Papillomavirus Status: The Foundation of Risk-Based Cervical Screening Guidelines.

    Science.gov (United States)

    Demarco, Maria; Lorey, Thomas S; Fetterman, Barbara; Cheung, Li C; Guido, Richard S; Wentzensen, Nicolas; Kinney, Walter K; Poitras, Nancy E; Befano, Brian; Castle, Philip E; Schiffman, Mark

    2017-10-01

    The next round of the American Society for Colposcopy and Cervical Pathology (ASCCP)-sponsored cervical cancer screening and management guidelines will recommend clinical actions based on risk, rather than test-based algorithms. This article gives preliminary risk estimates for the screening setting, showing combinations of the 2 most important predictors, human papillomavirus (HPV) status and cytology result. Among 1,262,713 women aged 25 to 77 years co-tested with HC2 (Qiagen) and cytology at Kaiser Permanente Northern California, we estimated 0-5-year cumulative risk of cervical intraepithelial neoplasia (CIN) 2+, CIN 3+, and cancer for combinations of cytology (negative for intraepithelial lesion or malignancy [NILM], atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL], atypical squamous cells cannot exclude HSIL [ASC-H], high-grade squamous intraepithelial lesion [HSIL], atypical glandular cells [AGC]) and HPV status. Ninety percent of screened women had HPV-negative NILM and an extremely low risk of subsequent cancer. Five-year risks of CIN 3+ were lower after HPV negativity (0.12%) than after NILM (0.25%). Among HPV-negative women, 5-year risks for CIN 3+ were 0.10% for NILM, 0.44% for ASC-US, 1.8% for LSIL, 3.0% for ASC-H, 1.2% for AGC, and 29% for HSIL+ cytology (which was very rare). Among HPV-positive women, 5-year risks were 4.0% for NILM, 6.8% for ASC-US, 6.1% for LSIL, 28% for ASC-H, 30% for AGC, and 50% for HSIL+ cytology. As a foundation for the next guidelines revision, we confirmed with additional precision the risk estimates previously reported for combinations of HPV and cytology. Future analyses will estimate risks for women being followed in colposcopy clinic and posttreatment and will consider the role of risk modifiers such as age, HPV vaccine status, HPV type, and screening and treatment history.

  9. Pre-diagnostic plasma 25-hydroxyvitamin D levels and risk of non-melanoma skin cancer in women.

    Directory of Open Access Journals (Sweden)

    Geyu Liang

    Full Text Available Recent reports have shown that vitamin D status was inversely associated with the risk of various cancers. However, few studies examined the association between vitamin D levels and risk of skin cancer.We prospectively evaluated the association between baseline plasma 25(OHD levels and the risk of incident squamous cell carcinoma (SCC and basal cell carcinoma (BCC among 4,641 women from the Nurses' Health Study (NHS and the NHS II with 510 incident BCC cases and 75 incident SCC cases. We used multivariate logistic regression models to calculate odds ratios (ORs and 95% confidence intervals (CIs.Plasma 25(OHD levels were positively associated with risk of BCC after adjusting for age at blood draw, season of blood draw, lab batch, hair color, burning tendency, the number of sunburns, and ultra-violet B flux of residence at blood collection. Women in the highest quartile of 25(OHD had more than 2-fold increased risk of BCC compared with women in the lowest quartile (OR = 2.07, 95% CI = 1.52-2.80, P for trend <0.0001. We also found a significantly positive association between plasma 25(OHD levels and SCC risk after adjusting for the same covariates (OR, highest vs. lowest quartile = 3.77, 95% CI = 1.70-8.36, P for trend= 0.0002.In this prospective study of women, plasma vitamin D levels were positively associated with non-melanoma skin cancer risk. Considering that most circulating vitamin D is due to sun exposure, the positive association between plasma vitamin D and non-melanoma skin cancer is confounded by sun exposure. Our data suggest that one-time measurement of plasma vitamin D levels may reasonably reflect long-term sun exposure and predict the risk of non-melanoma skin cancer.

  10. Modulating Cancer Risk: The Gut Takes Control | Center for Cancer Research

    Science.gov (United States)

    Cancer risk is influenced by a number of factors, including exposure to chemicals in food and drugs and other molecules in the environment. Some of these chemicals may increase risk of developing cancer, while others, including many chemicals in vegetables, may confer protection.

  11. Obesity and colorectal cancer risk

    International Nuclear Information System (INIS)

    Hano Garcia, Olga Marina; Wood Rodriguez, Lisette; Villa Jimenez, Oscar Manuel

    2011-01-01

    Obesity is a chronic and multifactor disease characterized by presence of excess body fat harmful for health. Several studies have been conducted to assess the possible risk character of different factors for colorectal cancer including the following modifying factors: a diet rich in saturated fats, a diet low in vegetables, physical inactivity, alcohol consumption and obesity. A case-control study was conducted to include 276 adult patients (93 cases and 184 controls) consecutively seen from May, 2008 to May, 2009 in the Institute of Gastroenterology determining a possible association between obesity as risk factor and colorectal cancer. Variables measures included: sex, age, skin color, body mass index, hip-waist circumference and endoscopic location of cancer. We conclude that the colorectal cancer with predominance in female sex and in white people in both groups. Obesity according to a great relation hip-waist had an strong relation with colorectal cancer, which had predominance towards distal colon in both sexes

  12. How the growth rate of host cells affects cancer risk in a deterministic way

    Science.gov (United States)

    Draghi, Clément; Viger, Louise; Denis, Fabrice; Letellier, Christophe

    2017-09-01

    It is well known that cancers are significantly more often encountered in some tissues than in other ones. In this paper, by using a deterministic model describing the interactions between host, effector immune and tumor cells at the tissue level, we show that this can be explained by the dependency of tumor growth on parameter values characterizing the type as well as the state of the tissue considered due to the "way of life" (environmental factors, food consumption, drinking or smoking habits, etc.). Our approach is purely deterministic and, consequently, the strong correlation (r = 0.99) between the number of detectable growing tumors and the growth rate of cells from the nesting tissue can be explained without evoking random mutation arising during DNA replications in nonmalignant cells or "bad luck". Strategies to limit the mortality induced by cancer could therefore be well based on improving the way of life, that is, by better preserving the tissue where mutant cells randomly arise.

  13. Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact

    Directory of Open Access Journals (Sweden)

    Hidehiko Takigawa

    2017-05-01

    Full Text Available We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow–derived mesenchymal stem cells (MSCs migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important. We performed a microarray analysis of gene expression in KM12SM colon cancer cells directly cocultured with MSCs. Expression of epithelial-mesenchymal transition (EMT–related genes such as fibronectin (FN, SPARC, and galectin 1 was increased by direct coculture with MSCs. We also confirmed the upregulation of these genes with real-time polymerase chain reaction. Gene expression was not elevated in cancer cells indirectly cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture with MSCs, we examined the immune localization of FN, a well-known EMT marker. In coculture assay in chamber slides, expression of FN was seen only at the edges of cancer clusters where cancer cells directly contacted MSCs. FN expression in cancer cells increased at the tumor periphery and invasive edge in orthotopic nude mouse tumors and human colon cancer tissues. These results suggest that MSCs induce EMT in colon cancer cells via direct cell-to-cell contact and may play an important role in colon cancer metastasis.

  14. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  15. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  16. Ionizing radiation induces stemness in cancer cells.

    Directory of Open Access Journals (Sweden)

    Laura Ghisolfi

    Full Text Available The cancer stem cell (CSC model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation-induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.

  17. Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

    Directory of Open Access Journals (Sweden)

    Ina Bähr

    2017-01-01

    Full Text Available Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity.

  18. Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

    Science.gov (United States)

    Bista, Rajan K.; Uttam, Shikhar; Hartman, Douglas J.; Qiu, Wei; Yu, Jian; Zhang, Lin; Brand, Randall E.; Liu, Yang

    2012-06-01

    The development of accurate and clinically applicable tools to assess cancer risk is essential to define candidates to undergo screening for early-stage cancers at a curable stage or provide a novel method to monitor chemoprevention treatments. With the use of our recently developed optical technology--spatial-domain low-coherence quantitative phase microscopy (SL-QPM), we have derived a novel optical biomarker characterized by structure-derived optical path length (OPL) properties from the cell nucleus on the standard histology and cytology specimens, which quantifies the nano-structural alterations within the cell nucleus at the nanoscale sensitivity, referred to as nano-morphology marker. The aim of this study is to evaluate the feasibility of the nuclear nano-morphology marker from histologically normal cells, extracted directly from the standard histology specimens, to detect early-stage carcinogenesis, assess cancer risk, and monitor the effect of chemopreventive treatment. We used a well-established mouse model of spontaneous carcinogenesis--ApcMin mice, which develop multiple intestinal adenomas (Min) due to a germline mutation in the adenomatous polyposis coli (Apc) gene. We found that the nuclear nano-morphology marker quantified by OPL detects the development of carcinogenesis from histologically normal intestinal epithelial cells, even at an early pre-adenomatous stage (six weeks). It also exhibits a good temporal correlation with the small intestine that parallels the development of carcinogenesis and cancer risk. To further assess its ability to monitor the efficacy of chemopreventive agents, we used an established chemopreventive agent, sulindac. The nuclear nano-morphology marker is reversed toward normal after a prolonged treatment. Therefore, our proof-of-concept study establishes the feasibility of the SL-QPM derived nuclear nano-morphology marker OPL as a promising, simple and clinically applicable biomarker for cancer risk assessment and

  19. Improvement of the projection models for radiogenic cancer risk

    International Nuclear Information System (INIS)

    Tong Jian

    2005-01-01

    Calculations of radiogenic cancer risk are based on the risk projection models for specific cancer sites. Improvement has been made for the parameters used in the previous models including introductions of mortality and morbidity risk coefficients, and age-/ gender-specific risk coefficients. These coefficients have been applied to calculate the radiogenic cancer risks for specific organs and radionuclides under different exposure scenarios. (authors)

  20. Epigenetic Biomarkers of Breast Cancer Risk: Across the Breast Cancer Prevention Continuum.

    Science.gov (United States)

    Terry, Mary Beth; McDonald, Jasmine A; Wu, Hui Chen; Eng, Sybil; Santella, Regina M

    2016-01-01

    Epigenetic biomarkers, such as DNA methylation, can increase cancer risk through altering gene expression. The Cancer Genome Atlas (TCGA) Network has demonstrated breast cancer-specific DNA methylation signatures. DNA methylation signatures measured at the time of diagnosis may prove important for treatment options and in predicting disease-free and overall survival (tertiary prevention). DNA methylation measurement in cell free DNA may also be useful in improving early detection by measuring tumor DNA released into the blood (secondary prevention). Most evidence evaluating the use of DNA methylation markers in tertiary and secondary prevention efforts for breast cancer comes from studies that are cross-sectional or retrospective with limited corresponding epidemiologic data, raising concerns about temporality. Few prospective studies exist that are large enough to address whether DNA methylation markers add to the prediction of tertiary and secondary outcomes over and beyond standard clinical measures. Determining the role of epigenetic biomarkers in primary prevention can help in identifying modifiable pathways for targeting interventions and reducing disease incidence. The potential is great for DNA methylation markers to improve cancer outcomes across the prevention continuum. Large, prospective epidemiological studies will provide essential evidence of the overall utility of adding these markers to primary prevention efforts, screening, and clinical care.

  1. Cancer risks and prevention

    International Nuclear Information System (INIS)

    Vessey, M.P.; Gray, M.

    1985-01-01

    A series of essays in honour of Sir Richard Doll is presented. Chapters cover the preventability of cancer, geography, smoking, diet, occupation, radiation, infections and immune impairment, exogenous and endogenous hormones, other drugs, prevention through legislation and by education and cancer risks and prevention in the Third World. The chapter on radiation has been indexed separately. (UK)

  2. Annexins are instrumental for efficient plasma membrane repair in cancer cells.

    Science.gov (United States)

    Lauritzen, Stine Prehn; Boye, Theresa Louise; Nylandsted, Jesper

    2015-09-01

    Plasma membrane stress can cause damage to the plasma membrane, both when imposed by the extracellular environment and by enhanced oxidative stress. Cells cope with these injuries by rapidly activating their plasma membrane repair system, which is triggered by Ca(2+) influx at the wound site. The repair system is highly dynamic, depends on both lipid and protein components, and include cytoskeletal reorganization, membrane replacements, and membrane fusion events. Cancer cells experience enhanced membrane stress when navigating through dense extracellular matrix, which increases the frequency of membrane injuries. In addition, increased motility and oxidative stress further increase the risk of plasma membrane lesions. Cancer cells compensate by overexpressing Annexin proteins including Annexin A2 (ANXA2). Annexin family members can facilitate membrane fusion events and wound healing by binding to negatively charged phospholipids in the plasma membrane. Plasma membrane repair in cancer cells depends on ANXA2 protein, which is recruited to the wound site and forms a complex with the Ca(2+)-binding EF-hand protein S100A11. Here they regulate actin accumulation around the wound perimeter, which is required for wound closure. In this review, we will discuss the requirement for Annexins, S100 proteins and actin cytoskeleton in the plasma membrane repair response of cancer cells, which reveals a novel avenue for targeting metastatic cancers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Radiation dose and second cancer risk in patients treated for cancer of the cervix

    International Nuclear Information System (INIS)

    Boice, J.D. Jr.; Engholm, G.; Kleinerman, R.A.

    1988-01-01

    The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors

  4. Human papilloma virus: a new risk factor in a subset of head and neck cancers.

    Science.gov (United States)

    Bisht, Manisha; Bist, Sampan Singh

    2011-01-01

    Head and neck cancer is the sixth most common malignancy worldwide. Tobacco smoking and alcohol consumption are two well known behavioral risk factors associated with head and neck cancer. Recently, evidence is mounting that infection with human papilloma virus, most commonly human papilloma virus-16 is responsible for a subset of head and neck squamous cell carcinoma especially tumors of tonsillar origin. The molecular pathway used by human papilloma virus to trigger malignant transformation of tissue is different from that of other well known risk factors, i.e. smoking and alcohol, associated with squamous cell carcinoma. Apparently, these subsets of patients with human papilloma virus positive tumor are more likely to have a better prognosis than human papilloma virus negative tumor. Considering this fact, the human papilloma virus infection should be determined in all oropharyngeal cancers since it can have a major impact on the decision making process of the treatment.

  5. Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Blanca L Valle

    Full Text Available Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.

  6. T-cell activation promotes tumorigenesis in inflammation-associated cancer

    Directory of Open Access Journals (Sweden)

    Lairmore Michael

    2009-12-01

    Full Text Available Abstract Chronic inflammation has long been associated with a wide range of malignancies, is now widely accepted as a risk factor for development of cancer, and has been implicated as a promoter of a variety of cancers including hematopoietic malignancies. We have described a mouse model uniquely suited to examine the link between inflammation and lymphoma in which the Tax oncogene, expressed in activated T and NK cells, perpetuates chronic inflammation that begins as microscopic intraepithelial lesions and develops into inflammatory nodules, subcutaneous tumors, and large granular lymphocytic leukemia. The use of bioluminescent imaging in these mice has expanded our ability to interrogate aspects of inflammation and tumorigenesis non-invasively. Here we demonstrate that bioluminescence induction in these mice correlated with inflammation resulting from wounding, T cell activation, and exposure to chemical agents. In experiments in which long-term effects of inflammation on disease outcome were monitored, the development of lymphoma was promoted by an inflammatory stimulus. Finally we demonstrated that activation of T-cells in T-cell receptor (TCR transgenic TAX-LUC animals dramatically exacerbated the development of subcutaneous TCR- CD16+ LGL tumors. The role of activated T-cells and acquired immunity in inflammation-associated cancers is broadly applicable to hematopoietic malignancies, and we propose these mice will be of use in dissecting mechanisms by which activated T-cells promote lymphomagenesis in vivo.

  7. Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

    Energy Technology Data Exchange (ETDEWEB)

    Boukheris, Houda [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Stovall, Marilyn [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gilbert, Ethel S. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Stratton, Kayla L. [Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Smith, Susan A.; Weathers, Rita [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hammond, Sue [Department of Pathology, Ohio State University School of Medicine, Columbus, Ohio (United States); Mertens, Ann C. [Department of Pediatrics, Emory University, Atlanta, Georgia (United States); Donaldson, Sarah S. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Armstrong, Gregory T.; Robison, Leslie L. [Department of Epidemiology and Cancer Control, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Neglia, Joseph P. [Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Inskip, Peter D., E-mail: inskippe@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-03-01

    Purpose: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Methods and Materials: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. Results: During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Conclusion: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.

  8. Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

    International Nuclear Information System (INIS)

    Boukheris, Houda; Stovall, Marilyn; Gilbert, Ethel S.; Stratton, Kayla L.; Smith, Susan A.; Weathers, Rita; Hammond, Sue; Mertens, Ann C.; Donaldson, Sarah S.; Armstrong, Gregory T.; Robison, Leslie L.; Neglia, Joseph P.; Inskip, Peter D.

    2013-01-01

    Purpose: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Methods and Materials: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. Results: During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Conclusion: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies

  9. Extinction models for cancer stem cell therapy

    Science.gov (United States)

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

    2012-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives

  10. Obesity-associated Breast Cancer: Analysis of risk factors.

    Science.gov (United States)

    Engin, Atilla

    2017-01-01

    Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Furthermore, obese women are at higher risk of all-cause and breast cancer specific mortality when compared to non-obese women with breast cancer. In this context, increased levels of estrogens due to excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, hyperactivation of insulin-like growth factors (IGFs) pathways, adipocyte-derived adipokines, hypercholesterolemia and excessive oxidative stress contribute to the development of breast cancer in obese women. While higher breast cancer risk with hormone replacement therapy is particularly evident among lean women, in postmenopausal women who are not taking exogenous hormones, general obesity is a significant predictor for breast cancer. Moreover, increased plasma cholesterol leads to accelerated tumor formation and exacerbates their aggressiveness. In contrast to postmenopausal women, premenopausal women with high BMI are inversely associated with breast cancer risk. Nevertheless, life-style of women for breast cancer risk is regulated by avoiding the overweight and a high-fat diet. Estrogen-plus-progestin hormone therapy users for more than 5 years have elevated risks of both invasive ductal and lobular breast cancer. Additionally, these cases are more commonly node-positive and have a higher cancer-related mortality. Collectively, in this chapter, the impacts of obesity-related estrogen, cholesterol, saturated fatty acid, leptin and adiponectin concentrations, aromatase activity, leptin and insulin resistance on breast cancer patients are evaluated. Obesity-related prognostic factors of breast cancer also are discussed at molecular basis.

  11. Cancer risk awareness and screening uptake in individuals at higher risk for colon cancer: a cross-sectional study.

    Science.gov (United States)

    Salimzadeh, Hamideh; Bishehsari, Faraz; Delavari, Alireza; Barzin, Gilda; Amani, Mohammad; Majidi, Azam; Sadjadi, Alireza; Malekzadeh, Reza

    2016-12-20

    We aimed to measure cancer knowledge and feasibility of a screening colonoscopy among a cohort of individuals at higher risk of colon cancer. This study was conducted as part of an ongoing screening cohort, in which first degree relatives (FDRs) of patients with colon cancer are invited to participate in a free of charge screening colonoscopy. We enrolled 1017 FDRs in the study between 2013 and 2014 measuring their data on demographics, cancer knowledge and colonoscopy uptake. A p value of aware of their increased risk for cancer, near 35.0% had ever heard about colonoscopy with 22% aware of the correct age to start screening. Comparing cancer knowledge of FDRs at high risk versus those at moderate risk, we recorded non-significant differences (p>0.05). Almost two-thirds of FDRs expressed willingness to undergo a colonoscopy and 49.2% completed the procedure, of which 12.8% had advanced neoplasm. Our data indicated that remarkable numbers of FDRs were not still informed of their cancer risk or never received a physician recommendation for screening. The desirable uptake at first invitation, which would be higher over successive invitations, supports the feasibility of a family-based recruitment approach for early screening. This has promising implications to introduce targeted screening colonoscopy into the healthcare system in Iran and other developing nations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Ji, S.Q.; Cao, J.; Zhang, Q.Y.; Li, Y.Y.; Yan, Y.Q.; Yu, F.X.

    2013-01-01

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis

  13. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

    2013-09-27

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

  14. Geographical variance in the risk of gastric stump cancer: no increased risk in Japan?

    NARCIS (Netherlands)

    Tersmette, A. C.; Giardiello, F. M.; Offerhaus, G. J.; Tersmette, K. W.; Ohara, K.; Vandenbroucke, J. P.; Tytgat, G. N.

    1991-01-01

    Geographical differences may exist in the risk of gastric stump cancer. Therefore, we performed meta-analysis of literature reports in Japan (n = 3), the USA (n = 4), and Europe (n = 20) on the risk of postgastrectomy cancer. The weighted mean relative risk of stump cancer in Japan was 0.28, 95%

  15. Graphs to estimate an individualized risk of breast cancer.

    Science.gov (United States)

    Benichou, J; Gail, M H; Mulvihill, J J

    1996-01-01

    Clinicians who counsel women about their risk for developing breast cancer need a rapid method to estimate individualized risk (absolute risk), as well as the confidence limits around that point. The Breast Cancer Detection Demonstration Project (BCDDP) model (sometimes called the Gail model) assumes no genetic model and simultaneously incorporates five risk factors, but involves cumbersome calculations and interpolations. This report provides graphs to estimate the absolute risk of breast cancer from the BCDDP model. The BCDDP recruited 280,000 women from 1973 to 1980 who were monitored for 5 years. From this cohort, 2,852 white women developed breast cancer and 3,146 controls were selected, all with complete risk-factor information. The BCDDP model, previously developed from these data, was used to prepare graphs that relate a specific summary relative-risk estimate to the absolute risk of developing breast cancer over intervals of 10, 20, and 30 years. Once a summary relative risk is calculated, the appropriate graph is chosen that shows the 10-, 20-, or 30-year absolute risk of developing breast cancer. A separate graph gives the 95% confidence limits around the point estimate of absolute risk. Once a clinician rules out a single gene trait that predisposes to breast cancer and elicits information on age and four risk factors, the tables and figures permit an estimation of a women's absolute risk of developing breast cancer in the next three decades. These results are intended to be applied to women who undergo regular screening. They should be used only in a formal counseling program to maximize a woman's understanding of the estimates and the proper use of them.

  16. Periodontal disease with treatment reduces subsequent cancer risks.

    Science.gov (United States)

    Hwang, Ing-Ming; Sun, Li-Min; Lin, Cheng-Li; Lee, Chun-Feng; Kao, Chia-Hung

    2014-10-01

    The aim of our study was to evaluate the relationship between routine treatment of periodontal disease (PD) and the subsequent risks for cancers in Taiwan. Study participants were selected from the Taiwan National Health Insurance (NHI) system database. The PD with a routine treatment cohort contained 38 902 patients. For each treatment cohort participant, two age- and sex-matched comparison (control) cohort participants were randomly selected. Cox's proportional hazards regression analysis was used to estimate the effects of PD with treatment on the subsequent risk of cancer. The overall risk of developing cancer was significantly lower in the treatment cohort than in the patients without treatment (adjusted Hazard ratio = 0.72, 95% confidence interval = 0.68-0.76). The risks of developing most gastrointestinal tract, lung, gynecological and brain malignancies were significantly lower in the treatment cohort than in the comparison cohort. In contrast, the risks of prostate and thyroid cancers were significantly higher in the treatment cohort than in the comparison cohort. Our findings suggest that PD with treatment is associated with a significantly reduced overall risk of cancer and reduced risks of certain types of cancers. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Sun protection for preventing basal cell and squamous cell skin cancers.

    Science.gov (United States)

    Sánchez, Guillermo; Nova, John; Rodriguez-Hernandez, Andrea Esperanza; Medina, Roger David; Solorzano-Restrepo, Carolina; Gonzalez, Jenny; Olmos, Miguel; Godfrey, Kathie; Arevalo-Rodriguez, Ingrid

    2016-07-25

    'Keratinocyte cancer' is now the preferred term for the most commonly identified skin cancers basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), which were previously commonly categorised as non-melanoma skin cancers (NMSC). Keratinocyte cancer (KC) represents about 95% of malignant skin tumours. Lifestyle changes have led to increased exposure to the sun, which has, in turn, led to a significant increase of new cases of KC, with a worldwide annual incidence of between 3% and 8%. The successful use of preventive measures could mean a significant reduction in the resources used by health systems, compared with the high cost of the treatment of these conditions. At present, there is no information about the quality of the evidence for the use of these sun protection strategies with an assessment of their benefits and risks. To assess the effects of sun protection strategies (i.e. sunscreen and barrier methods) for preventing keratinocyte cancer (that is, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) of the skin) in the general population. We searched the following databases up to May 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registries and the bibliographies of included studies for further references to relevant trials. We included randomised controlled clinical trials (RCTs) of preventive strategies for keratinocyte cancer, such as physical barriers and sunscreens, in the general population (children and adults), which may provide information about benefits and adverse events related to the use of solar protection measures. We did not include trials focused on educational strategies to prevent KC or preventive strategies in high-risk groups. Our prespecified primary outcomes were BCC or cSCC confirmed clinically or by histopathology at any follow-up and adverse events. Two review authors independently selected studies for eligibility using

  18. Update on breast cancer risk prediction and prevention.

    Science.gov (United States)

    Sestak, Ivana; Cuzick, Jack

    2015-02-01

    Breast cancer is the most common cancer in women worldwide. This review will focus on current prevention strategies for women at high risk. The identification of women who are at high risk of developing breast cancer is key to breast cancer prevention. Recent findings have shown that the inclusion of breast density and a panel of low-penetrance genetic polymorphisms can improve risk estimation compared with previous models. Preventive therapy with aromatase inhibitors has produced large reductions in breast cancer incidence in postmenopausal women. Tamoxifen confers long-term protection and is the only proven preventive treatment for premenopausal women. Several other agents, including metformin, bisphosphonates, aspirin and statins, have been found to be effective in nonrandomized settings. There are many options for the prevention of oestrogen-positive breast cancer, in postmenopausal women who can be given a selective oestrogen receptor modulator or an aromatase inhibitor. It still remains unclear how to prevent oestrogen-negative breast cancer, which occurs more often in premenopausal women. Identification of women at high risk of the disease is crucial, and the inclusion of breast density and a panel of genetic polymorphisms, which individually have low penetrance, can improve risk assessment.

  19. Exploring the uncertainties in cancer risk assessment using the integrated probabilistic risk assessment (IPRA) approach.

    Science.gov (United States)

    Slob, Wout; Bakker, Martine I; Biesebeek, Jan Dirk Te; Bokkers, Bas G H

    2014-08-01

    Current methods for cancer risk assessment result in single values, without any quantitative information on the uncertainties in these values. Therefore, single risk values could easily be overinterpreted. In this study, we discuss a full probabilistic cancer risk assessment approach in which all the generally recognized uncertainties in both exposure and hazard assessment are quantitatively characterized and probabilistically evaluated, resulting in a confidence interval for the final risk estimate. The methodology is applied to three example chemicals (aflatoxin, N-nitrosodimethylamine, and methyleugenol). These examples illustrate that the uncertainty in a cancer risk estimate may be huge, making single value estimates of cancer risk meaningless. Further, a risk based on linear extrapolation tends to be lower than the upper 95% confidence limit of a probabilistic risk estimate, and in that sense it is not conservative. Our conceptual analysis showed that there are two possible basic approaches for cancer risk assessment, depending on the interpretation of the dose-incidence data measured in animals. However, it remains unclear which of the two interpretations is the more adequate one, adding an additional uncertainty to the already huge confidence intervals for cancer risk estimates. © 2014 Society for Risk Analysis.

  20. The Cell-CT 3D Cell Imaging Technology Platform Enables the Detection of Lung Cancer Using the Non-Invasive LuCED Sputum Test

    Science.gov (United States)

    Meyer, Michael G.; Hayenga, Jon; Neumann, Thomas; Katdare, Rahul; Presley, Chris; Steinhauer, David; Bell, Timothy; Lancaster, Christy; Nelson, Alan C.

    2015-01-01

    The war against cancer has yielded important advances in the early diagnosis and treatment of certain cancer types, but the poor detection rate and 5-year survival rate for lung cancer remains little changed over the past 40 years. Early detection through emerging lung cancer screening programs promises the most reliable means of improving mortality. Sputum cytology has been tried without success because sputum contains few malignant cells that are difficult for cytologists to detect. However, research has shown that sputum contains diagnostic malignant cells and could serve as a means of lung cancer detection if those cells could be detected and correctly characterized. Recently, the National Lung Cancer Screening Trial reported that screening by three consecutive low-dose X-ray CT scans provides a 20% reduction in lung cancer mortality compared to chest X-ray. This reduction in mortality, however, comes with an unacceptable false positive rate that increases patient risks and the overall cost of lung cancer screening. This article reviews the LuCED® test for detecting early lung cancer. LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell-CT®, which images cells in three dimensions with sub-micron resolution. Algorithms are applied to the 3D cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist's manual review. LuCED promotes accurate cell classification which could enable cost effective detection of lung cancer. PMID:26148817

  1. Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells

    International Nuclear Information System (INIS)

    Teng, Ying; Wang, Xiuwen; Wang, Yawei; Ma, Daoxin

    2010-01-01

    Wnt/β-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that β-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of β-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of β-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/β-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.

  2. Targeting Stromal-Cancer Cell Crosstalk Networks in Ovarian Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tsz-Lun Yeung

    2016-01-01

    Full Text Available Ovarian cancer is a histologically, clinically, and molecularly diverse disease with a five-year survival rate of less than 30%. It has been estimated that approximately 21,980 new cases of epithelial ovarian cancer will be diagnosed and 14,270 deaths will occur in the United States in 2015, making it the most lethal gynecologic malignancy. Ovarian tumor tissue is composed of cancer cells and a collection of different stromal cells. There is increasing evidence that demonstrates that stromal involvement is important in ovarian cancer pathogenesis. Therefore, stroma-specific signaling pathways, stroma-derived factors, and genetic changes in the tumor stroma present unique opportunities for improving the diagnosis and treatment of ovarian cancer. Cancer-associated fibroblasts (CAFs are one of the major components of the tumor stroma that have demonstrated supportive roles in tumor progression. In this review, we highlight various types of signaling crosstalk between ovarian cancer cells and stromal cells, particularly with CAFs. In addition to evaluating the importance of signaling crosstalk in ovarian cancer progression, we discuss approaches that can be used to target tumor-promoting signaling crosstalk and how these approaches can be translated into potential ovarian cancer treatment.

  3. Higher Heart Failure Risk Seen in Some Cancers

    Science.gov (United States)

    Some people treated for breast cancer or lymphoma have a higher risk of developing congestive heart failure than people who haven’t had cancer, a new study shows. As this Cancer Currents blog post reports, the risk persisted for at least 20 years.

  4. Pregnancy-related venous thromboembolism and risk of occult cancer

    DEFF Research Database (Denmark)

    Tarp Hansen, Anette; Veres, Katalin; Horváth-Puhó, Erzsébet

    2017-01-01

    The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected.An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.......The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected.An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk....

  5. Pregnancy-related venous thromboembolism and risk of occult cancer

    DEFF Research Database (Denmark)

    Hansen, Anette Tarp; Veres, Katalin; Horváth-Puhó, Erzsébet

    2017-01-01

    The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected. An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.......The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected. An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk....

  6. COPD and squamous cell lung cancer: aberrant inflammation and immunity is the common link.

    Science.gov (United States)

    Bozinovski, Steven; Vlahos, Ross; Anthony, Desiree; McQualter, Jonathan; Anderson, Gary; Irving, Louis; Steinfort, Daniel

    2016-02-01

    Cigarette smoking has reached epidemic proportions within many regions of the world and remains the highest risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Squamous cell lung cancer is commonly detected in heavy smokers, where the risk of developing lung cancer is not solely defined by tobacco consumption. Although therapies that target common driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related squamous cell lung cancer. Since COPD is characterized by an excessive inflammatory and oxidative stress response, this review details how aberrant innate, adaptive and systemic inflammatory processes can contribute to lung cancer susceptibility in COPD. Activated leukocytes release increasing levels of proteases and free radicals as COPD progresses and tertiary lymphoid aggregates accumulate with increasing severity. Reactive oxygen species promote formation of reactive carbonyls that are not only tumourigenic through initiating DNA damage, but can directly alter the function of regulatory proteins involved in host immunity and tumour suppressor functions. Systemic inflammation is also markedly increased during infective exacerbations in COPD and the interplay between tumour-promoting serum amyloid A (SAA) and IL-17A is discussed. SAA is also an endogenous allosteric modifier of FPR2 expressed on immune and epithelial cells, and the therapeutic potential of targeting this receptor is proposed as a novel strategy for COPD-lung cancer overlap. © 2015 The British Pharmacological Society.

  7. Prospective study of blood metabolites associated with colorectal cancer risk.

    Science.gov (United States)

    Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

    2018-02-26

    Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

  8. Anatomic Subsite of Primary Colorectal Cancer and Subsequent Risk and Distribution of Second Cancers

    Science.gov (United States)

    Phipps, Amanda I.; Chan, Andrew T.; Shuji Ogino, MD

    2013-01-01

    Background Individuals with a history of colorectal cancer (CRC) have an increased risk of subsequent cancer. We used cancer registry data to evaluate whether this increased risk of cancer after CRC differed by anatomic subsite of a first CRC. Methods Individuals diagnosed with first primary CRC between 1992–2009 were identified from 12 Surveillance Epidemiology and End Results (SEER) cancer registries. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) comparing the incidence of subsequent cancers in these index CRC cases to cancer incidence rates in the general population. SIRs were calculated for cancers at anatomic sites within and outside the colorectum in analyses stratified by subsite of the index CRC. Results Cancer incidence rates were significantly higher in those with prior CRC than in the general population (SIR=1.15, 95% CI: 1.13–1.16). Individuals with an index CRC located between the transverse and descending colon experienced the greatest increased risk both overall (SIR=1.29 to 1.33), and with respect to risk of second CRC in particular (SIR=2.53 to 3.35). Incidence of small intestinal cancer was significantly elevated regardless of index CRC subsite (SIR=4.31, 95% CI: 3.70–4.77); incidence of endometrial cancer was elevated in those with index CRC in the proximal colon (SIR=1.37 to 1.79). Conclusions Risk of second cancer after CRC differs by anatomic site of the first tumor, and is particularly pronounced for those with prior CRC located in the transverse to descending colon. The mechanisms underlying this pattern of second cancer risk remain unknown. PMID:23856984

  9. Cancer risk factors in Korean news media: a content analysis.

    Science.gov (United States)

    Kye, Su Yeon; Kwon, Jeong Hyun; Kim, Yong-Chan; Shim, Minsun; Kim, Jee Hyun; Cho, Hyunsoon; Jung, Kyu Won; Park, Keeho

    2015-01-01

    Little is known about the news coverage of cancer risk factors in Korea. This study aimed to examine how the news media encompasses a wide array of content regarding cancer risk factors and related cancer sites, and investigate whether news coverage of cancer risk factors is congruent with the actual prevalence of the disease. A content analysis was conducted on 1,138 news stories covered during a 5-year period between 2008 and 2012. The news stories were selected from nationally representative media in Korea. Information was collected about cancer risk factors and cancer sites. Of various cancer risk factors, occupational and environmental exposures appeared most frequently in the news. Breast cancer was mentioned the most in relation to cancer sites. Breast, cervical, prostate, and skin cancer were overrepresented in the media in comparison to incidence and mortality cases, whereas lung, thyroid, liver, and stomach cancer were underrepresented. To our knowledge, this research is the first investigation dealing with news coverage about cancer risk factors in Korea. The study findings show occupational and environmental exposures are emphasized more than personal lifestyle factors; further, more prevalent cancers in developed countries have greater media coverage, not reflecting the realities of the disease. The findings may help health journalists and other health storytellers to develop effective ways to communicate cancer risk factors.

  10. Genetic variability of the mTOR pathway and prostate cancer risk in the European Prospective Investigation on Cancer (EPIC.

    Directory of Open Access Journals (Sweden)

    Daniele Campa

    2011-02-01

    Full Text Available The mTOR (mammalian target of rapamycin signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC. We chose the SNPs (n = 11 with the strongest association with risk (p<0.01 and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (OR(allele = 0.85, 95% CI 0.78-0.94, p = 1.3 x 10⁻³ for rs546950 and OR(allele = 0.84, 95% CI 0.76-0.93, p = 5.6 x 10⁻⁴ for rs4955720. We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.

  11. Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness

    International Nuclear Information System (INIS)

    Xue, Jianguo; Zhu, Yuan; Sun, Zixuan; Ji, Runbi; Zhang, Xu; Xu, Wenrong; Yuan, Xiao; Zhang, Bin; Yan, Yongmin; Yin, Lei; Xu, Huijuan; Zhang, Leilei; Zhu, Wei; Qian, Hui

    2015-01-01

    Emerging evidence indicates that inappropriate cell-cell fusion might contribute to cancer progression. Similarly, mesenchymal stem cells (MSCs) can also fuse with other cells spontaneously and capable of adopting the phenotype of other cells. The aim of our study was to investigate the role of MSCs participated cell fusion in the tumorigenesis of gastric cancer. We fused human umbilical cord mesenchymal stem cells (hucMSCs) with gastric cancer cells in vitro by polyethylene glycol (PEG), the hybrid cells were sorted by flow cytometer. The growth and migration of hybrids were assessed by cell counting, cell colony formation and transwell assays. The proteins and genes related to epithelial-mesenchymal transition and stemness were tested by western blot, immunocytochemistry and real-time RT-PCR. The expression of CD44 and CD133 was examined by immunocytochemistry and flow cytometry. The xenograft assay was used to evaluation the tumorigenesis of the hybrids. The obtained hybrids exhibited epithelial- mesenchymal transition (EMT) change with down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, α-smooth muscle actin (α-SMA), and fibroblast activation protein (FAP). The hybrids also increased expression of stemness factors Oct4, Nanog, Sox2 and Lin28. The expression of CD44 and CD133 on hybrid cells was stronger than parental gastric cancer cells. Moreover, the migration and proliferation of heterotypic hybrids were enhanced. In addition, the heterotypic hybrids promoted the growth abilities of gastric xenograft tumor in vivo. Taken together, our results suggest that cell fusion between hucMSCs and gastric cancer cells could contribute to tumorigenic hybrids with EMT and stem cell-like properties, which may provide a flexible tool for investigating the roles of MSCs in gastric cancer. The online version of this article (doi:10.1186/s12885-015-1780-1) contains supplementary material, which is available to authorized users

  12. Nature, Nurture, and Cancer Risks: Genetic and Nutritional Contributions to Cancer.

    Science.gov (United States)

    Theodoratou, Evropi; Timofeeva, Maria; Li, Xue; Meng, Xiangrui; Ioannidis, John P A

    2017-08-21

    It is speculated that genetic variants are associated with differential responses to nutrients (known as gene-diet interactions) and that these variations may be linked to different cancer risks. In this review, we critically evaluate the evidence across 314 meta-analyses of observational studies and randomized controlled trials of dietary risk factors and the five most common cancers (breast, lung, prostate, colorectal, and stomach). We also critically evaluate the evidence across 13 meta-analyses of observational studies of gene-diet interactions for the same cancers. Convincing evidence for association was found only for the intake of alcohol and whole grains in relation to colorectal cancer risk. Three nutrient associations had highly suggestive evidence and another 15 associations had suggestive evidence. Among the examined gene-diet interactions, only one had moderately strong evidence.

  13. Indoor Tanning and the MC1R Genotype: Risk Prediction for Basal Cell Carcinoma Risk in Young People

    OpenAIRE

    Molinaro, Annette M.; Ferrucci, Leah M.; Cartmel, Brenda; Loftfield, Erikka; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

    2015-01-01

    Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients...

  14. Immuno-related polymorphisms and cervical cancer risk: The IARC multicentric case-control study.

    Directory of Open Access Journals (Sweden)

    James McKay

    Full Text Available A small proportion of women who are exposed to infection with human-papillomavirus (HPV develop cervical cancer (CC. Genetic factors may affect the risk of progression from HPV infection to cervical precancer and cancer. We used samples from the International Agency for Research on Cancer (IARC multicentric case-control study to evaluate the association of selected genetic variants with CC. Overall, 790 CC cases and 717 controls from Algeria, Morocco, India and Thailand were included. Cervical exfoliated cells were obtained from control women and cervical exfoliated cells or biopsy specimens from cases. HPV-positivity was determined using a general primer GP5+/6+ mediated PCR. Unconditional logistic regression was used to estimate odds ratios (OR and corresponding 95% confidence intervals (CI of host genotypes with CC risk, using the homozygous wild type genotype as the referent category and adjusting by age and study centre. The association of polymorphisms with the risk of high-risk HPV-positivity among controls was also evaluated. A statistically significant association was observed between single nucleotide polymorphism (SNP CHR6 rs2844511 and CC risk: the OR for carriers of the GA or GG genotypes was 0.70 (95% CI: 0.43-1.14 and 0.61 (95% CI: 0.38-0.98, respectively, relative to carriers of AA genotype (p-value for trend 0.03. We also observed associations of borderline significance with the TIPARP rs2665390 polymorphism, which was previously found to be associated with ovarian and breast cancer, and with the EXOC1 rs13117307 polymorphism, which has been linked to cervical cancer in a large study in a Chinese population. We confirmed the association between CC and the rs2844511 polymorphism previously identified in a GWAS study in a Swedish population. The major histocompatibility region of chromosome 6, or perhaps other SNPs in linkage disequilibrium, may be involved in CC onset.

  15. Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer.

    Science.gov (United States)

    Hadaschik, Boris; Su, Yun; Huter, Eva; Ge, Yingzi; Hohenfellner, Markus; Beckhove, Philipp

    2012-04-01

    Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-γ secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  16. Gene polymorphisms and oral cancer risk in tobacco habitués.

    Science.gov (United States)

    Multani, Shaleen; Pradhan, Sultan; Saranath, Dhananjaya

    2016-05-01

    Oral cancer incidence of 77,003 poses a major health concern in India, with 5-10 % tobacco habitués developing oral cancer. The current study examined the role of specific genomic variants in oral cancer. We examined five genomic variants represented as single nucleotide polymorphisms (SNPs) in genes associated with cell proliferation and cellular invasion. The SNPs rs2124437 (RASGRP3), rs1335022 (GRIK2), rs4512367 (PREX2), rs4748011 (CCDC3), and rs1435218 (LNX1) were analyzed in 500 histopathologically confirmed oral cancers and 500 healthy controls with a minimum of 10 years of tobacco usage. Allelic discrimination real-time PCR SYBR Green assay was used. The genotypic and allelic frequencies between cases and controls were analyzed using SPSS software (version 19) and odds ratio (OR) using Hutchon.net, indicating increased risk to oral cancers. A significant association of the SNPs in oral cancer was observed in RASGRP3 AA (rs2124437) (p oral cancer in tobacco habitués.

  17. Indoor tanning in businesses and homes and risk of melanoma and nonmelanoma skin cancer in 2 US case-control studies.

    Science.gov (United States)

    Ferrucci, Leah M; Vogel, Rachel Isaksson; Cartmel, Brenda; Lazovich, DeAnn; Mayne, Susan T

    2014-11-01

    Indoor tanning increases skin cancer risk. Beyond early research describing melanoma and sun lamps, few recent reports describe where individuals indoor tan and whether skin cancer risk varies by location (business, home-based). We sought to assess where individuals tanned indoors and skin cancer risk by tanning device location. Multivariate logistic regression was conducted in 2 US case-control studies of melanoma (1161 cases, 1083 controls, ages 25-59 years) and early-onset basal cell carcinoma (375 cases, 382 controls, agetanned exclusively in businesses. Persons who used indoor tanning exclusively in businesses were at increased risk of melanoma (odds ratio 1.82, 95% confidence interval 1.47-2.26) and basal cell carcinoma (odds ratio 1.69, 95% confidence interval 1.15-2.48) compared with non-users. Melanoma risk was also increased in the small number who reported tanning indoors only at home relative to non-users (odds ratio 4.14, 95% confidence interval 1.75-9.78); 67.6% used sun lamps. Self-reported tanning and potential recall bias are limitations. Business-only tanning, despite claims of "safe" tanning, was positively associated with a significant risk of melanoma and basal cell carcinoma. Home tanning was uncommon and mostly from sun lamps, which were rarely used by younger participants. Regardless of location, indoor tanning was associated with increased risk of skin cancer. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  18. Occupational exposure to diesel engine emissions and risk of lung cancer: evidence from two case-control studies in Montreal, Canada.

    Science.gov (United States)

    Pintos, Javier; Parent, Marie-Elise; Richardson, Lesley; Siemiatycki, Jack

    2012-11-01

    To examine the risk of lung cancer among men associated with exposure to diesel engine emissions incurred in a wide range of occupations and industries. 2 population-based lung cancer case-control studies were conducted in Montreal. Study I (1979-1986) comprised 857 cases and 533 population controls; study II (1996-2001) comprised 736 cases and 894 population controls. A detailed job history was obtained, from which we inferred lifetime occupational exposure to 294 agents, including diesel engine emissions. ORs were estimated for each study and in the pooled data set, adjusting for socio-demographic factors, smoking history and selected occupational carcinogens. While it proved impossible to retrospectively estimate absolute exposure concentrations, there were estimates and analyses by relative measures of cumulative exposure. Increased risks of lung cancer were found in both studies. The pooled analysis showed an OR of lung cancer associated with substantial exposure to diesel exhaust of 1.80 (95% CI 1.3 to 2.6). The risk associated with substantial exposure was higher for squamous cell carcinomas (OR 2.09; 95% CI 1.3 to 3.2) than other histological types. Joint effects between diesel exhaust exposure and tobacco smoking are compatible with a multiplicative synergistic effect. Our findings provide further evidence supporting a causal link between diesel engine emissions and risk of lung cancer. The risk is stronger for the development of squamous cell carcinomas than for small cell tumours or adenocarcinomas.

  19. Genetic variants of JNK and p38α pathways and risk of non-small cell lung cancer in an Eastern Chinese population.

    Science.gov (United States)

    Jia, Ming; Zhu, Meiling; Zhou, Fei; Wang, Mengyun; Sun, Menghong; Yang, Yajun; Wang, Xiaofeng; Wang, Jiucun; Jin, Li; Xiang, Jiaqing; Zhang, Yawei; Chang, Jianhua; Wei, Qingyi

    2017-02-15

    The JNK and p38α pathways play an important role in carcinogenesis. Therefore, we hypothesize that single nucleotide polymorphisms (SNPs) of genes involved in these pathways are associated with risk of lung cancer. We first selected and genotyped 11 independent SNPs of the JNK and p38α pathway-related genes in a discovery set of 1,002 non-small cell lung cancer (NSCLC) cases and 1,025 cancer-free controls of Eastern Chinese. Then, we validated those significant SNPs in a replication set of 1,333 NSCLC cases and 1,339 cancer-free controls of Eastern Chinese. Multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses were used to identify interactions between significant SNPs and other covariates. In both discovery and replication as well as their pooled analysis, carriers of GADD45G rs8252T variant genotypes had a significantly lower risk of NSCLC (adjusted OR = 0.81 and 0.79, 95% CI = 0.72-0.92 and 0.64-0.99 and p = 0.001 and 0.040 for dominant and recessive genetic models, respectively) and carriers of MAP2K7 rs3679T variant genotypes had an increased risk of NSCLC (adjusted OR = 1.19 and 1.29, 95% CI = 1.05-1.34 and 1.09-1.54 and p = 0.005 and 0.004 for dominant and recessive genetic models, respectively). Furthermore, rs8252 variant CT/TT carriers showed significantly higher levels of GADD45G mRNA expression than CC carriers in the target tissues. We observed some evidence of interactions between rs8252 genotypes and sex in NSCLC risk. These results indicate that GADD45G rs8252 and MAP2K7 rs3679 SNPs may be susceptibility biomarkers for NSCLC in Eastern Chinese populations. © 2016 UICC.

  20. Comparative polymorphism of BAT-26 between healthy individuals and cancer patients and its cancer risk implication for local Chinese.

    Science.gov (United States)

    Zheng, Yanying; Liu, Li; Sun, Yi; Chen, Jie; Wang, Jianrong; Zhu, Changle; Lai, Rensheng; Xie, Ling

    2016-07-30

    BAT-26 is one of the representative markers for microsatellite instability evaluation and presents different polymorphisms in different ethnic populations. The current knowledge of its comparative polymorphism between healthy individuals and cancer patients in the Chinese population is insufficient. This study aims to analyze germline polymorphic variations of BAT-26 between healthy individuals and cancer patients in Chinese from Jiangsu province and the associated cancer risk implications. The various BAT-26 alleles and their percentages in cervical cells from 500 healthy women were assessed by direct sequencing. Twenty of these samples were also analyzed by fragment analysis. BAT-26 of blood DNA from 24 healthy individuals and 247 cancer patients was analyzed by fragment analysis. Compared with the sequencing results, 122.6-122.9 bp, 123.4-123.8 bp and 124.1-124.8 bp corresponded to the A25, A26 and A27 alleles, respectively. The 524 healthy individuals showed 4.58%, 92.18% and 3.24% of A25, A26 and A27, respectively. The variant alleles A18, A24, A28, A29 and A32 were only found in cancer patients, accounting for 0.81%, 0.40%, 0.40%, 0.40% and 0.40%, respectively; the A25, A26 and A27 alleles in cancer patients accounted for 6.48%, 77.33% and 13.77%. Healthy individuals had a stable BAT-26 profile within the quasimonomorphic variation range (QMVR), but cancer patients harbored variant alleles outside QMVR and showed a trend from quasimonomorph to polymonomorph, suggesting that variant alleles of BAT-26 in germline cells may be regarded as a potential marker of higher cancer risk in the Chinese population from Jiangsu province.

  1. Cancer in first-degree relatives and risk of testicular cancer in Denmark

    Science.gov (United States)

    Nordsborg, Rikke Baastrup; Meliker, Jaymie R.; Wohlfahrt, Jan; Melbye, Mads; Raaschou-Nielsen, Ole

    2011-01-01

    Familial aggregation of testicular cancer has been reported consistently, but it is less clear if there is any association between risk of testicular cancer and other cancers in the family. We conducted a population based case-control study to examine the relationship between risk of testicular cancer and 22 different cancers in first-degree relatives. We included 3297 cases of testicular cancer notified to the Danish Cancer Registry between 1991 and 2003. 6594 matched controls were selected from the Danish Civil Registration System, which also provided the identity of 40,104 first-degree relatives of case and controls. Familial cancer was identified by linkage to the Danish Cancer Registry, and we used conditional logistic regression to analyse whether cancer among first-degree relatives was associated with higher risk of testicular cancer. Rate ratio (RR) for testicular cancer was 4.63 (95% CI: 2.41–8.87) when a father, 8.30(95% CI: 3.81–18.10) when a brother and 5.23 (95% CI: 1.35–20.26) when a son had testicular cancer compared with no familial testicular cancer. Results were similar when analyses were stratified by histologic subtypes of testicular cancer. Familial Non-Hodgkin lymphoma and oesophageal cancer were associated with testicular cancer; however these may be chance findings. The familial aggregation of testicular and possibly other cancers may be explained by shared genes and/or shared environmental factors, but the mutual importance of each of these is difficult to determine. PMID:21207375

  2. The Implications of Cancer Stem Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wenjing Jiang

    2012-12-01

    Full Text Available Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Recent studies have showed that cancer stem cells (CSCs, a small subpopulation of tumor cells, can generate bulk populations of nontumorigenic cancer cell progeny through the self-renewal and differentiation processes. As CSCs are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors, development of CSC-targeted therapeutic strategies holds new hope for improving survival and quality of life in patients with cancer. Therapeutic innovations will emerge from a better understanding of the biology and environment of CSCs, which, however, are largely unexplored. This review summarizes the characteristics, evidences and development of CSCs, as well as implications and challenges for cancer treatment.

  3. Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention.

    Directory of Open Access Journals (Sweden)

    Yongping Bao

    Full Text Available The isothiocyanate (ITC sulforaphane (SFN was shown at low levels (1-5 µM to promote cell proliferation to 120-143% of the controls in a number of human cell lines, whilst at high levels (10-40 µM it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control, whereas at 10-20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint.

  4. Early life risk factors for testicular cancer

    DEFF Research Database (Denmark)

    Piltoft, Johanne Spanggaard; Larsen, Signe Benzon; Dalton, Susanne Oksbjerg

    2017-01-01

    of this study is to utilize data from the Copenhagen School Health Records Register (CSHRR) to evaluate cryptorchidism, birth weight and birth order as risk factors for testicular cancer. METHODS: The study population consisted of 408 cases of testicular cancer identified by a government issued identification...... in crude analyses [hazard ratio (HR) = 3.60, 95% CI 2.79-4.65]. Birth weight was inversely associated with testicular cancer and no clear association with birth order was observed. The positive association between cryptorchidism and testicular cancer was only slightly attenuated controlling for birth......PURPOSE: One established risk factors for testicular cancer is cryptorchidism. However, it remains unclear whether cryptorchidism is a risk factor in itself or whether the two conditions share common causes in early life (estrogen hypothesis), such as birth weight and birth order. The objective...

  5. A POX on Renal Cancer Cells | Center for Cancer Research

    Science.gov (United States)

    Proline oxidase, or POX, is an enzyme responsible for metabolizing the amino acid proline. POX contributes to the regulation of cell death that occurs when cellular systems malfunction, a process called apoptosis. Previous studies have determined that levels of POX are reduced in several types of human cancer. Likewise, many cancer cells become resistant to apoptosis, suggesting a link between POX and cancer cell survival.

  6. Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT polymorphism in a prospective cohort study among women in China.

    Directory of Open Access Journals (Sweden)

    Qing Lan

    Full Text Available A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR, 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003. Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030. Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations.

  7. The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Cristiano Capurso

    2017-08-01

    Full Text Available Prostate cancer is the second most common cancer in the world among men, and is the fifth most common cause of cancer death among men. The aim of our review was to analyze observational and case–control studies to point out the effects of overweight and diets components on the cancer risk, particularly on risk of prostate cancer, and the effect of the Mediterranean diet (MD on the reduction of risk and mortality of prostate cancer. It is known that incidence and progression of cancer is multifactorial. Cancer of the large bowel, breast, endometrium, and prostate are due also to a high body mass index and to high consumption of high carcinogenic dietary factors, as red and processed meat or saturated fats rich foods, and to a low consumption of vegetables and fruits. Previous meta-analysis suggested that high adherence to diet model based on the traditional MD pattern gives a significant protection from incidence and mortality of cancer of all types. The main component of the MD is olive oil, consumed in high amount by Mediterranean basin populations. In addition, phenolic compounds exert some strong chemo-preventive effects, which are due to several mechanisms, including both antioxidant effects and actions on cancer cell signaling and cell cycle progression and proliferation. The protective effect of the MD against the prostate cancer is also due to the high consumption of tomato sauce. Lycopene is the most relevant functional component in tomatoes; after activating by the cooking of tomato sauce, it exerts antioxidant properties by acting in the modulation of downregulation mechanisms of the inflammatory response. MD, therefore, represents a healthy dietary pattern in the context of a healthy lifestyle habits. In conclusion, our narrative review allows us to reaffirm how nutritional factors play an important role in cancer initiation and development, and how a healthy dietary pattern represented by MD and its components, especially olive oil

  8. Triiodothyronine regulates cell growth and survival in renal cell cancer.

    Science.gov (United States)

    Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

    2016-10-01

    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

  9. Model Checking of a Diabetes-Cancer Model

    Science.gov (United States)

    Gong, Haijun; Zuliani, Paolo; Clarke, Edmund M.

    2011-06-01

    Accumulating evidence suggests that cancer incidence might be associated with diabetes mellitus, especially Type II diabetes which is characterized by hyperinsulinaemia, hyperglycaemia, obesity, and overexpression of multiple WNT pathway components. These diabetes risk factors can activate a number of signaling pathways that are important in the development of different cancers. To systematically understand the signaling components that link diabetes and cancer risk, we have constructed a single-cell, Boolean network model by integrating the signaling pathways that are influenced by these risk factors to study insulin resistance, cancer cell proliferation and apoptosis. Then, we introduce and apply the Symbolic Model Verifier (SMV), a formal verification tool, to qualitatively study some temporal logic properties of our diabetes-cancer model. The verification results show that the diabetes risk factors might not increase cancer risk in normal cells, but they will promote cell proliferation if the cell is in a precancerous or cancerous stage characterized by losses of the tumor-suppressor proteins ARF and INK4a.

  10. Squamous cell lung cancer in a male with pulmonary tuberculosis.

    Science.gov (United States)

    Skowroński, Marcin; Iwanik, Katarzyna; Halicka, Anna; Barinow-Wojewódzki, Aleksander

    2015-01-01

    Lung cancer and pulmonary tuberculosis (TB) are highly prevalent and representing major public health issues. They share common risk factors and clinical manifestations. It is also suggested that TB predicts raised lung cancer risk likely related to chronic inflammation in the lungs. However, it does not seem to influence the clinical course of lung cancer provided that it is properly treated. We present a case report of a 57-year old male with concurrent TB and lung cancer. He was diagnosed with positive sputum smear for acid fast bacilli (AFB) and subsequent culture of Mycobacterium tuberculosis. Besides, his comorbid conditions were chronic hepatitis C virus (HCV) infection and peripheral artery disease (PAD). Later while on anti-tuberculous treatment (ATT) squamous cell lung cancer (SCC) was confirmed with computed tomography (CT) guided biopsy. Due to poor general condition the patient was not fit for either surgery or radical chemo- and radiotherapy. He was transferred to hospice for palliative therapy. We want to emphasize that both TB and lung cancer should be actively sought for in patients with either disorder. In addition, there is no doubt that these patients with lung cancer and with good response to TB treatment should be promptly considered for appropriate anticancer therapy.

  11. Cancer risk in children born after donor ART.

    Science.gov (United States)

    Williams, C L; Bunch, K J; Murphy, M F G; Stiller, C A; Botting, B J; Wallace, W H; Davies, M C; Sutcliffe, A G

    2018-01-01

    Do children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population? This study showed no overall increased risk of childhood cancer in individuals born after donor ART. Most large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date. This retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992-2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years). Records of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992-2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles. In our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43-1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an

  12. Gastric cancer stem cells: A novel therapeutic target

    Science.gov (United States)

    Singh, Shree Ram

    2013-01-01

    Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

  13. Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study

    International Nuclear Information System (INIS)

    Nan, Hongmei; Qureshi, Abrar A; Hunter, David J; Han, Jiali

    2009-01-01

    The human fibroblast growth factor (FGF) and its receptor (FGFR) play an important role in tumorigenesis. Deregulation of the FGFR2 gene has been identified in a number of cancer sites. Overexpression of the FGFR4 protein has been linked to cutaneous melanoma progression. Previous studies reported associations between genetic variants in the FGFR2 and FGFR4 genes and development of various cancers. We evaluated the associations of four genetic variants in the FGFR2 gene highly related to breast cancer risk and the three common tag-SNPs in the FGFR4 gene with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 controls. We found no evidence for associations between these seven genetic variants and the risks of melanoma and nonmelanocytic skin cancer. Given the power of this study, we did not detect any contribution of genetic variants in the FGFR2 or FGFR4 genes to inherited predisposition to skin cancer among Caucasian women

  14. Estrogen Drives Cellular Transformation and Mutagenesis in Cells Expressing the Breast Cancer-Associated R438W DNA Polymerase Lambda Protein.

    Science.gov (United States)

    Nemec, Antonia A; Bush, Korie B; Towle-Weicksel, Jamie B; Taylor, B Frazier; Schulz, Vincent; Weidhaas, Joanne B; Tuck, David P; Sweasy, Joann B

    2016-11-01

    Repair of DNA damage is critical for maintaining the genomic integrity of cells. DNA polymerase lambda (POLL/Pol λ) is suggested to function in base excision repair (BER) and nonhomologous end-joining (NHEJ), and is likely to play a role in damage tolerance at the replication fork. Here, using next-generation sequencing, it was discovered that the POLL rs3730477 single-nucleotide polymorphism (SNP) encoding R438W Pol λ was significantly enriched in the germlines of breast cancer patients. Expression of R438W Pol λ in human breast epithelial cells induces cellular transformation and chromosomal aberrations. The role of estrogen was assessed as it is commonly used in hormone replacement therapies and is a known breast cancer risk factor. Interestingly, the combination of estrogen treatment and the expression of the R438W Pol λ SNP drastically accelerated the rate of transformation. Estrogen exposure produces 8-oxoguanine lesions that persist in cells expressing R438W Pol λ compared with wild-type (WT) Pol λ-expressing cells. Unlike WT Pol λ, which performs error-free bypass of 8-oxoguanine lesions, expression of R438W Pol λ leads to an increase in mutagenesis and replicative stress in cells treated with estrogen. Together, these data suggest that individuals who carry the rs3730477 POLL germline variant have an increased risk of estrogen-associated breast cancer. The Pol λ R438W mutation can serve as a biomarker to predict cancer risk and implicates that treatment with estrogen in individuals with this mutation may further increase their risk of breast cancer. Mol Cancer Res; 14(11); 1068-77. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. Cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells (MSCs).

    Science.gov (United States)

    Bartosh, Thomas J; Ullah, Mujib; Zeitouni, Suzanne; Beaver, Joshua; Prockop, Darwin J

    2016-10-18

    Patients with breast cancer often develop malignant regrowth of residual drug-resistant dormant tumor cells years after primary treatment, a process defined as cancer relapse. Deciphering the causal basis of tumor dormancy therefore has obvious therapeutic significance. Because cancer cell behavior is strongly influenced by stromal cells, particularly the mesenchymal stem/stromal cells (MSCs) that are actively recruited into tumor-associated stroma, we assessed the impact of MSCs on breast cancer cell (BCC) dormancy. Using 3D cocultures to mimic the cellular interactions of an emerging tumor niche, we observed that MSCs sequentially surrounded the BCCs, promoted formation of cancer spheroids, and then were internalized/degraded through a process resembling the well-documented yet ill-defined clinical phenomenon of cancer cell cannibalism. This suspected feeding behavior was less appreciable in the presence of a rho kinase inhibitor and in 2D monolayer cocultures. Notably, cannibalism of MSCs enhanced survival of BCCs deprived of nutrients but suppressed their tumorigenicity, together suggesting the cancer cells entered dormancy. Transcriptome profiles revealed that the resulting BCCs acquired a unique molecular signature enriched in prosurvival factors and tumor suppressors, as well as inflammatory mediators that demarcate the secretome of senescent cells, also referred to as the senescence-associated secretory phenotype. Overall, our results provide intriguing evidence that cancer cells under duress enter dormancy after cannibalizing MSCs. Importantly, our practical 3D coculture model could provide a valuable tool to understand the antitumor activity of MSCs and cell cannibalism further, and therefore open new therapeutic avenues for the prevention of cancer recurrence.

  16. Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study

    Science.gov (United States)

    Moskowitz, Chaya S.; Chou, Joanne F.; Bradbury, Angela R.; Neglia, Joseph Phillip; Dang, Chau T.; Onel, Kenan; Novetsky Friedman, Danielle; Bhatia, Smita; Strong, Louise C.; Stovall, Marilyn; Kenney, Lisa B.; Barnea, Dana; Lorenzi, Elena; Hammond, Sue; Leisenring, Wendy M.; Robison, Leslie L.; Armstrong, Gregory T.; Diller, Lisa R.; Oeffinger, Kevin C.

    2016-01-01

    Purpose Little is known about the breast cancer risk among childhood cancer survivors who did not receive chest radiotherapy. We sought to determine the magnitude of risk and associated risk factors for breast cancer among these women. Patients and Methods We evaluated cumulative breast cancer risk in 3,768 female childhood cancer survivors without a history of chest radiotherapy who were participants in the Childhood Cancer Survivor Study. Results With median follow up of 25.5 years (range, 8 to 39 years), 47 women developed breast cancer at a median age of 38.0 years (range, 22 to 47 years) and median of 24.0 years (range, 10 to 34 years) from primary cancer to breast cancer. A four-fold increased breast cancer risk (standardized incidence ratio [SIR] = 4.0; 95% CI, 3.0 to 5.3) was observed when compared with the general population. Risk was highest among sarcoma and leukemia survivors (SIR = 5.3; 95% CI, 3.6 to 7.8 and SIR = 4.1; 95% CI, 2.4 to 6.9, respectively). By the age of 45 years, the cumulative incidence of breast cancer in sarcoma and leukemia survivors was 5.8% (95% CI, 3.7 to 8.4) and 6.3% (95% CI, 3.0 to 11.3), respectively. No other primary cancer diagnosis was associated with an elevated risk. Alkylators and anthracyclines were associated with an increased breast cancer risk in a dose-dependent manner (P values from test for trend were both < .01). Conclusions Women not exposed to chest radiotherapy who survive childhood sarcoma or leukemia have an increased risk of breast cancer at a young age. The data suggest high-dose alkylator and anthracycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study. PMID:26700127

  17. Risk perception among Brazilian individuals with high risk for colorectal cancer and colonoscopy

    Directory of Open Access Journals (Sweden)

    Santos Erika M

    2011-07-01

    Full Text Available Abstract Background Risk perception is considered a motivating factor for adopting preventive behaviors. This study aimed to verify the demographic characteristics and cancer family history that are predictors of risk perception and to verify if risk perception is a predictor of colonoscopy adherence. Methods Individuals with a family colorectal cancer history as indicated by a proband with cancer were interviewed by telephone. They responded to a questionnaire covering demographic characteristics, colonoscopy history and four questions on risk perception. Tests of multiple linear regression and logistic regression were used to identify associations between dependent and independent variables. Results The 117 participants belonged to 62 families and had a mean age of 45.2 years. The majority of these individuals were female (74.4% and from families who met the Amsterdam Criteria (54.7%. The average risk perception was 47.6%, with a median of 50%. The average population perception of individual risk was 55.4%, with a median of 50%. Variables associated with a higher risk perception were age, gender, religion, school level, income, and death of a family member. The variable predicting colonoscopy was receiving medical information regarding risk (odds ratio OR 8.40. Conclusions We found that family cancer history characteristics (number of relatives with cancer, risk classification are associated with adequate risk perception. Risk perception does not predict colonoscopy in this sample. The only variable that predicted colonoscopy was receiving medical information recommending screening.

  18. Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

    Science.gov (United States)

    Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

    2017-08-10

    One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Cancer Risk Map for the Surface of Mars

    Science.gov (United States)

    Kim, Myung-Hee Y.; Cucinotta, Francis A.

    2011-01-01

    We discuss calculations of the median and 95th percentile cancer risks on the surface of Mars for different solar conditions. The NASA Space Radiation Cancer Risk 2010 model is used to estimate gender and age specific cancer incidence and mortality risks for astronauts exploring Mars. Organ specific fluence spectra and doses for large solar particle events (SPE) and galactic cosmic rays (GCR) at various levels of solar activity are simulated using the HZETRN/QMSFRG computer code, and the 2010 version of the Badhwar and O Neill GCR model. The NASA JSC propensity model of SPE fluence and occurrence is used to consider upper bounds on SPE fluence for increasing mission lengths. In the transport of particles through the Mars atmosphere, a vertical distribution of Mars atmospheric thickness is calculated from the temperature and pressure data of Mars Global Surveyor, and the directional cosine distribution is implemented to describe the spherically distributed atmospheric distance along the slant path at each elevation on Mars. The resultant directional shielding by Mars atmosphere at each elevation is coupled with vehicle and body shielding for organ dose estimates. Astronaut cancer risks are mapped on the global topography of Mars, which was measured by the Mars Orbiter Laser Altimeter. Variation of cancer risk on the surface of Mars is due to a 16-km elevation range, and the large difference is obtained between the Tharsis Montes (Ascraeus, Pavonis, and Arsia) and the Hellas impact basin. Cancer incidence risks are found to be about 2-fold higher than mortality risks with a disproportionate increase in skin and thyroid cancers for all astronauts and breast cancer risk for female astronauts. The number of safe days on Mars to be below radiation limits at the 95th percent confidence level is reported for several Mission design scenarios.

  20. Prenatal and perinatal risk factors and testicular cancer: a hospital-based case-control study.

    Science.gov (United States)

    Sonke, Gabe S; Chang, Shine; Strom, Sara S; Sweeney, Anne M; Annegers, J Fred; Sigurdson, Alice J

    2007-01-01

    Some evidence exists to support the hypothesis that elevated levels of circulating maternal estrogens during early pregnancy may increase risk of testicular germ cell cancer. However, the results from studies evaluating maternal factors have been mixed. We evaluated maternal factors, particularly those associated with excess estrogen levels, as risk factors for testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center in Houston, Texas of 144 testicular cancer patients diagnosed between 1990 and 1996 and 86 friend controls matched to cases on age, race, and state of residence. Risk factor data about the mother, the son, and the pregnancy were obtained from the mothers by telephone interviews and from the sons by self-administered questionnaires. Extreme nausea during the first trimester of pregnancy was associated with an elevated risk of testicular cancer [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.0-3.9]. Adjustment for potential confounders slightly lowered this risk (OR = 1.8; 95% CI = 0.9-3.8). Risks were modestly increased for other factors that are proxy measures for maternal estrogens, including preterm delivery (OR = 2.2; 95% CI = 0.4-12.9), birth weight 4000 g (OR = 1.7; 95% CI = 0.9-3.2), albeit nonsignificantly so. Our finding that severe nausea was associated with increased testicular cancer risk adds evidence to support the in utero estrogen exposure hypothesis because nausea early in pregnancy is related to rising levels of circulating estrogens. For other factors, which are less direct measures of maternal estrogens, the modest associations found indicate a suggestive pattern in support of the excess estrogen hypothesis.

  1. Osteoblast-Prostate Cancer Cell Interaction in Prostate Cancer Bone Metastases

    National Research Council Canada - National Science Library

    Navone, Nora

    2001-01-01

    .... This suggests that prostate cancer cells interact with cells from the osteoblastic lineage. To understand the molecular bases of prostatic bone metastases, we established two prostate cancer cell lines, MDA PCa 2a and MDA PCa 2b (1...

  2. High-dimensional single-cell cancer biology.

    Science.gov (United States)

    Irish, Jonathan M; Doxie, Deon B

    2014-01-01

    Cancer cells are distinguished from each other and from healthy cells by features that drive clonal evolution and therapy resistance. New advances in high-dimensional flow cytometry make it possible to systematically measure mechanisms of tumor initiation, progression, and therapy resistance on millions of cells from human tumors. Here we describe flow cytometry techniques that enable a "single-cell " view of cancer. High-dimensional techniques like mass cytometry enable multiplexed single-cell analysis of cell identity, clinical biomarkers, signaling network phospho-proteins, transcription factors, and functional readouts of proliferation, cell cycle status, and apoptosis. This capability pairs well with a signaling profiles approach that dissects mechanism by systematically perturbing and measuring many nodes in a signaling network. Single-cell approaches enable study of cellular heterogeneity of primary tissues and turn cell subsets into experimental controls or opportunities for new discovery. Rare populations of stem cells or therapy-resistant cancer cells can be identified and compared to other types of cells within the same sample. In the long term, these techniques will enable tracking of minimal residual disease (MRD) and disease progression. By better understanding biological systems that control development and cell-cell interactions in healthy and diseased contexts, we can learn to program cells to become therapeutic agents or target malignant signaling events to specifically kill cancer cells. Single-cell approaches that provide deep insight into cell signaling and fate decisions will be critical to optimizing the next generation of cancer treatments combining targeted approaches and immunotherapy.

  3. Colorectal cancer cells suppress CD4+ T cells immunity through canonical Wnt signaling.

    Science.gov (United States)

    Sun, Xuan; Liu, Suoning; Wang, Daguang; Zhang, Yang; Li, Wei; Guo, Yuchen; Zhang, Hua; Suo, Jian

    2017-02-28

    Understanding how colorectal cancer escapes from immunosurveillance and immune attack is important for developing novel immunotherapies for colorectal cancer. In this study we evaluated the role of canonical Wnt signaling in the regulation of T cell function in a mouse colorectal cancer model. We found that colorectal cancer cells expressed abundant Wnt ligands, and intratumoral T cells expressed various Frizzled proteins. Meanwhile, both active β-catenin and total β-catenin were elevated in intratumoral T cells. In vitro study indicated that colorectal cancer cells suppressed IFN-γ expression and increased IL-17a expression in activated CD4+ T cells. However, the cytotoxic activity of CD8+ T cells was not altered by colorectal cancer cells. To further evaluate the importance of Wnt signaling for CD4+ T cell-mediated cancer immunity, β-catenin expression was enforced in CD4+ T cells using lentiviral transduction. In an adoptive transfer model, enforced expression of β-catenin in intratumoral CD4+ T cells increased IL-17a expression, enhanced proliferation and inhibited apoptosis of colorectal cancer cells. Taken together, our study disclosed a new mechanism by which colorectal cancer impairs T cell immunity.

  4. Influence of family size and birth order on risk of cancer: a population-based study.

    Science.gov (United States)

    Bevier, Melanie; Weires, Marianne; Thomsen, Hauke; Sundquist, Jan; Hemminki, Kari

    2011-05-09

    Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family-Cancer Database to further analyze these effects. We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeconomic status. We divided the age at diagnosis in two groups, below and over 50 years, to identify the effect of family size and birth order for different age periods. Negative associations for increasing birth order were found for endometrial, testicular, skin, thyroid and connective tissue cancers and melanoma. In contrast, we observed positive association between birth order and lung, male and female genital cancers. Family size was associated with decreasing risk for endometrial and testicular cancers, melanoma and squamous cell carcinoma; risk was increased for leukemia and nervous system cancer. The effect of birth order decreased for lung and endometrial cancer from age at diagnosis below to over 50 years. Combined effects for birth order and family size were marginally significant for thyroid gland tumors. Especially, the relative risk for follicular thyroid gland tumors was significantly decreased for increasing birth order. Our findings suggest that the effect of birth order decreases from early to late adulthood for lung and endometrial cancer.

  5. Influence of family size and birth order on risk of cancer: a population-based study

    International Nuclear Information System (INIS)

    Bevier, Melanie; Weires, Marianne; Thomsen, Hauke; Sundquist, Jan; Hemminki, Kari

    2011-01-01

    Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family-Cancer Database to further analyze these effects. We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeconomic status. We divided the age at diagnosis in two groups, below and over 50 years, to identify the effect of family size and birth order for different age periods. Negative associations for increasing birth order were found for endometrial, testicular, skin, thyroid and connective tissue cancers and melanoma. In contrast, we observed positive association between birth order and lung, male and female genital cancers. Family size was associated with decreasing risk for endometrial and testicular cancers, melanoma and squamous cell carcinoma; risk was increased for leukemia and nervous system cancer. The effect of birth order decreased for lung and endometrial cancer from age at diagnosis below to over 50 years. Combined effects for birth order and family size were marginally significant for thyroid gland tumors. Especially, the relative risk for follicular thyroid gland tumors was significantly decreased for increasing birth order. Our findings suggest that the effect of birth order decreases from early to late adulthood for lung and endometrial cancer

  6. Influence of family size and birth order on risk of cancer: a population-based study

    Directory of Open Access Journals (Sweden)

    Sundquist Jan

    2011-05-01

    Full Text Available Abstract Background Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family-Cancer Database to further analyze these effects. Methods We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeconomic status. We divided the age at diagnosis in two groups, below and over 50 years, to identify the effect of family size and birth order for different age periods. Results Negative associations for increasing birth order were found for endometrial, testicular, skin, thyroid and connective tissue cancers and melanoma. In contrast, we observed positive association between birth order and lung, male and female genital cancers. Family size was associated with decreasing risk for endometrial and testicular cancers, melanoma and squamous cell carcinoma; risk was increased for leukemia and nervous system cancer. The effect of birth order decreased for lung and endometrial cancer from age at diagnosis below to over 50 years. Combined effects for birth order and family size were marginally significant for thyroid gland tumors. Especially, the relative risk for follicular thyroid gland tumors was significantly decreased for increasing birth order. Conclusion Our findings suggest that the effect of birth order decreases from early to late adulthood for lung and endometrial cancer.

  7. Genetic variant of miR-4293 rs12220909 is associated with susceptibility to non-small cell lung cancer in a Chinese Han population.

    Directory of Open Access Journals (Sweden)

    Lixia Fan

    Full Text Available Non-small cell lung cancer is one of the most common cancers and the leading cause of cancer death worldwide. Genetic variants in regulatory regions of some miRNAs might be involved in non-small cell lung cancer susceptibility and survival. rs12220909 (G/C genetic polymorphism in miR-4293 has been shown to be associated with decreased risk of esophageal squamous cell carcinoma. However, the influence of rs12220909 genetic variation on non-small cell lung cancer susceptibility has not been reported. In order to evaluate the potential association between miR-4293 rs12220909 and non-small cell lung cancer risk in a Chinese population, we performed a case-control study among 998 non-small cell lung cancer cases and 1471 controls. The data shows that miR-4293 rs12220909 was significantly associated with decreased susceptibility to non-small cell lung cancer (GC vs.GG: OR = 0.681, 95%CI = 0.555-0.835, P = 2.19E-4; GG vs. GC+CC: OR = 0.687, 95%CI = 0.564-0.837, P = 1.95E-4, which indicates that rs12220909 in miR-4293 may play a significant role in the development of non-small cell lung cancer.

  8. Association between dietary nitrate and nitrite intake and sitespecific cancer risk: evidence from observational studies.

    Science.gov (United States)

    Xie, Li; Mo, Miao; Jia, Hui-Xun; Liang, Fei; Yuan, Jing; Zhu, Ji

    2016-08-30

    Epidemiological studies have reported inconsistent findings on the association between dietary nitrate and nitrite intake and cancer risk. We performed a meta-analysis of epidemiological studies to summarize available evidence on the association between dietary nitrate and nitrite intake and cancer risk from published prospective and case-control studies. PubMed database was searched to identify eligible publications through April 30th, 2016. Study-specific relative risks (RRs) with corresponding 95% confidence interval (CI) from individual studies were pooled by using random- or fixed- model, and heterogeneity and publication bias analyses were conducted. Data from 62 observational studies, 49 studies for nitrates and 51 studies for nitrites, including a total of 60,627 cancer cases were analyzed. Comparing the highest vs. lowest levels, dietary nitrate intake was inversely associated with gastric cancer risk (RR = 0.78; 95%CI = 0.67-0.91) with moderate heterogeneity (I2 = 42.3%). In contrast, dietary nitrite intake was positively associated with adult glioma and thyroid cancer risk with pooled RR of 1.21 (95%CI = 1.03-1.42) and 1.52 (95%CI = 1.12-2.05), respectively. No significant associations were found between dietary nitrate/nitrite and cancers of the breast, bladder, colorectal, esophagus, renal cell, non-Hodgkin lymphoma, ovarian, and pancreas. The present meta-analysis provided modest evidence that positive associations of dietary nitrate and negative associations of dietary nitrite with certain cancers.

  9. Cancer risk in fathers and brothers of testicular cancer patients in Denmark. A population-based study.

    Science.gov (United States)

    Westergaard, T; Olsen, J H; Frisch, M; Kroman, N; Nielsen, J W; Melbye, M

    1996-05-29

    There are several reports of familial testicular cancer in the literature but few systematic attempts have been made to estimate the risk of testicular cancer in first-degree relatives of patients with this neoplasm, and the risk remains to be fully assessed in population-based studies. By means of data from the Danish Cancer Registry, we identified all testicular cancer patients (index cases) born and diagnosed during 1950-1993 in Denmark. Their fathers were identified from national registries, as were the brothers of a subcohort of these patients. Familial cancer occurrence was determined through linkage with the cancer registry and compared with the cancer incidence in the general male population in Denmark. The ratio of observed to expected cancers generated the measure used for the relative risk. Fathers of 2,113 index cases with testicular cancer experienced an almost 2-fold risk of developing testicular cancer themselves (RR = 1.96; 95% CI: 1.01-3.43). Overall, the fathers had a decreased relative cancer risk (RR = 0.84; 95% CI: 0.74-0.95) with a significantly decreased risk of cancers of the lung and digestive organs. Brothers of a subcohort of 702 index cases showed a markedly increased risk of testicular cancer (RR = 12.3; 95% CI: 3.3-3 1.5). In conclusion, we documented a significantly increased familial risk of testicular cancer which was relatively more pronounced between brothers than between fathers and sons. These findings support the possible involvement of a genetic component in the aetiology of testicular cancer, but also leave room for a hypothesized influence of in-utero exposures, such as specific maternal hormone levels, that might be shared by brothers.

  10. ADAMTS14 Gene Polymorphism and Environmental Risk in the Development of Oral Cancer.

    Directory of Open Access Journals (Sweden)

    Shih-Chi Su

    Full Text Available Oral cancer is a common malignancy that is shown to be causally associated with hereditary and acquired factors. ADAMTS14 is a member of the ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin motifs metalloproteinase family that plays an important role in extracellular matrix (ECM assembly and degradation. Elevation or deficiency of certain ADAMTS proteinases has been known to be implicated in a wide range of pathological processes including atherosclerosis, arthritis, and cancer. The present study aimed to explore the impact of ADAMTS14 gene polymorphisms, combined with environmental risks on the susceptibility to oral tumorigenesis.Four single-nucleotide polymorphisms (SNPs of the ADAMTS14 gene, including rs10823607, rs12774070, rs4747096, and rs61573157 were evaluated from 1200 normal controls and 850 patients with oral cancer. We failed to detect a significant association of four individual SNPs with oral cancer between case and control group. However, while considering behavioral exposure of environmental carcinogens, the presence of four ADAMTS14 SNPs, combined with betel nut chewing and/or smoking, profoundly leveraged the risk of oral cancer. Moreover, we observed a significant association of rs12774070, which is predicted to alter the expression and function of ADAMTS14 by in silico and bioinformatics analyses, with poor tumor cell differentiation (AOR: 0.59; 95% CI: 0.38-0.92; p = 0.02 in patients who chewed betel nuts.These results implicate the interaction between ADAMTS14 gene polymorphisms and environmental mutagens as a risk factor of oral tumorigenesis and suggest a correlation of rs12774070 with the degree of oral tumor cell differentiation.

  11. Reducing cancer risk in rural communities through supermarket interventions.

    Science.gov (United States)

    McCool, Barent N; Lyford, Conrad P; Hensarling, Natalie; Pence, Barbara; McCool, Audrey C; Thapa, Janani; Belasco, Eric; Carter, Tyra M

    2013-09-01

    Cancer risk is high, and prevention efforts are often minimal in rural communities. Feasible means of encouraging lifestyles that will reduce cancer risk for residents of rural communities are needed. This project developed and tested a model that could be feasibly adopted by rural communities to reduce cancer risk. This model focuses on incorporating multi-faceted cancer risk education in the local supermarket. As the supermarket functions both as the primary food source and an information source in small rural communities, the supermarket focus encourages the development of a community environment supportive of lifestyles that should reduce residents' risk for cancer. The actions taken to implement the model and the challenges that communities would have in implementing the model are identified.

  12. Cancer risk in systemic lupus

    DEFF Research Database (Denmark)

    Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Labrecque, Jeremy

    2013-01-01

    OBJECTIVE: To update estimates of cancer risk in SLE relative to the general population. METHODS: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. RESULTS: Across 30 c...

  13. Cancer risks after radiation exposures

    International Nuclear Information System (INIS)

    Voelz, G.L.

    1980-01-01

    A general overview of the effects of ionizing radiation on cancer induction is presented. The relationship between the degree of risk and absorbed dose is examined. Mortality from radiation-induced cancer in the US is estimated and percentages attributable to various sources are given

  14. High-risk populations identified in Childhood Cancer Survivor Study investigations: implications for risk-based surveillance.

    Science.gov (United States)

    Hudson, Melissa M; Mulrooney, Daniel A; Bowers, Daniel C; Sklar, Charles A; Green, Daniel M; Donaldson, Sarah S; Oeffinger, Kevin C; Neglia, Joseph P; Meadows, Anna T; Robison, Leslie L

    2009-05-10

    Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer.

  15. General Information about Small Cell Lung Cancer

    Science.gov (United States)

    ... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  16. Perceived cancer risk: why is it lower among nonwhites than whites?

    Science.gov (United States)

    Orom, Heather; Kiviniemi, Marc T; Underwood, Willie; Ross, Levi; Shavers, Vickie L

    2010-03-01

    We explored racial/ethnic differences in perceived cancer risk and determinants of these differences in a nationally representative sample of whites, blacks, Hispanics, and Asians. Multiple regression techniques, including mediational analyses, were used to identify determinants and quantify racial/ethnic differences in the perception of the risk of developing cancer among 5,581 adult respondents to the 2007 Health Information Trends Survey (HINTS). Blacks, Hispanics, and Asians reported lower perceived cancer risk than whites [Bs = -0.40, -0.34, and -0.69, respectively; (Ps risk were attenuated in older respondents because perceived cancer risk was negatively associated with age for whites but not for nonwhites. Nonwhites had lower perceptions of cancer risk than whites. Some of the racial/ethnic variability in perceived risk may be due to racial and ethnic differences in awareness of one's family history of cancer and its relevance for cancer risk, experiences with behavioral risk factors, and salience of cancer risk information.

  17. A comparative review of radiation-induced cancer risk models

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Hee; Kim, Ju Youl [FNC Technology Co., Ltd., Yongin (Korea, Republic of); Han, Seok Jung [Risk and Environmental Safety Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2017-06-15

    With the need for a domestic level 3 probabilistic safety assessment (PSA), it is essential to develop a Korea-specific code. Health effect assessments study radiation-induced impacts; in particular, long-term health effects are evaluated in terms of cancer risk. The objective of this study was to analyze the latest cancer risk models developed by foreign organizations and to compare the methodology of how they were developed. This paper also provides suggestions regarding the development of Korean cancer risk models. A review of cancer risk models was carried out targeting the latest models: the NUREG model (1993), the BEIR VII model (2006), the UNSCEAR model (2006), the ICRP 103 model (2007), and the U.S. EPA model (2011). The methodology of how each model was developed is explained, and the cancer sites, dose and dose rate effectiveness factor (DDREF) and mathematical models are also described in the sections presenting differences among the models. The NUREG model was developed by assuming that the risk was proportional to the risk coefficient and dose, while the BEIR VII, UNSCEAR, ICRP, and U.S. EPA models were derived from epidemiological data, principally from Japanese atomic bomb survivors. The risk coefficient does not consider individual characteristics, as the values were calculated in terms of population-averaged cancer risk per unit dose. However, the models derived by epidemiological data are a function of sex, exposure age, and attained age of the exposed individual. Moreover, the methodologies can be used to apply the latest epidemiological data. Therefore, methodologies using epidemiological data should be considered first for developing a Korean cancer risk model, and the cancer sites and DDREF should also be determined based on Korea-specific studies. This review can be used as a basis for developing a Korean cancer risk model in the future.

  18. Tumor mutational load and immune parameters across metastatic Renal Cell Carcinoma (mRCC) risk groups

    Science.gov (United States)

    de Velasco, Guillermo; Miao, Diana; Voss, Martin H.; Hakimi, A. Ari; Hsieh, James J.; Tannir, Nizar M.; Tamboli, Pheroze; Appleman, Leonard J.; Rathmell, W. Kimryn; Van Allen, Eliezer M.; Choueiri, Toni K.

    2016-01-01

    Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared to patients with favorable or intermediate-risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole exome transcriptome data in RCC patients (n = 54) included in The Cancer Genome Atlas that ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by MSKCC risk group, nor was the expression of cytolytic genes –granzyme A and perforin – or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis found that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. PMID:27538576

  19. High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

    2014-01-01

    OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid......-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up...... cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types. LEVEL OF EVIDENCE: II....

  20. Polymorphisms in RAI and in genes of nucleotide and base excision repair are not associated with risk of testicular cancer.

    Science.gov (United States)

    Laska, Magdalena J; Nexø, Bjørn A; Vistisen, Kirsten; Poulsen, Henrik Enghusen; Loft, Steffen; Vogel, Ulla

    2005-07-28

    Testicular cancer has been suggested to be primed in utero and there is familiar occurrence, particularly brothers and sons of men with testicular cancer have increased risk. Although no specific causative genotoxic agents have been identified, variations in DNA repair capacity could be associated with the risk of testicular cancer. A case-control study of 184 testicular cancer cases and 194 population-based controls living in the Copenhagen Greater Area in Denmark was performed. We found that neither polymorphisms in several DNA repair genes nor alleles of several polymorphisms in the chromosomal of region 19q13.2-3, encompassing the genes ASE, ERCC1, RAI and XPD, were associated with risk of testicular cancer in Danish patients. This is in contrast to other cancers, where we reported strong associations between polymorphisms in ERCC1, ASE and RAI and occurrence of basal cell carcinoma, breast cancer and lung. To our knowledge this is the first study of DNA repair gene polymorphisms and risk of testicular cancer.

  1. Mechanisms of Cancer Cell Dormancy--Another Hallmark of Cancer?

    Science.gov (United States)

    Yeh, Albert C; Ramaswamy, Sridhar

    2015-12-01

    Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. ©2015 American Association for Cancer Research.

  2. Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Steevens, J.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2011-01-01

    Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric

  3. Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis.

    Science.gov (United States)

    Benna, Clara; Helfrich-Förster, Charlotte; Rajendran, Senthilkumar; Monticelli, Halenya; Pilati, Pierluigi; Nitti, Donato; Mocellin, Simone

    2017-04-04

    The number of studies on the association between clock genes' polymorphisms and cancer susceptibility has increased over the last years but the results are often conflicting and no comprehensive overview and quantitative summary of the evidence in this field is available. Literature search identified 27 eligible studies comprising 96756 subjects (cases: 38231) and investigating 687 polymorphisms involving 14 clock genes. Overall, 1025 primary and subgroup meta-analyses on 366 gene variants were performed. Study distribution by tumor was as follows: breast cancer (n=15), prostate cancer (n=3), pancreatic cancer (n=2), non-Hodgkin's lymphoma (n=2), glioma (n=1), chronic lymphocytic leukemia (n=1), colorectal cancer (n=1), non-small cell lung cancer (n=1) and ovarian cancer (n=1).We identified 10 single nucleotide polymorphisms (SNPs) significantly associated with cancer risk: NPAS2 rs10165970 (mixed and breast cancer shiftworkers), rs895520 (mixed), rs17024869 (breast) and rs7581886 (breast); CLOCK rs3749474 (breast) and rs11943456 (breast); RORA rs7164773 (breast and breast cancer postmenopausal), rs10519097 (breast); RORB rs7867494 (breast cancer postmenopausal), PER3 rs1012477 (breast cancer subgroups) and assessed the level of quality evidence to be intermediate. We also identified polymorphisms with lower quality statistically significant associations (n=30). Our work supports the hypothesis that genetic variation of clock genes might affect cancer risk. These findings also highlight the need for more efforts in this research field in order to fully establish the contribution of clock gene variants to the risk of developing cancer. We conducted a systematic review and meta-analysis of the evidence on the association between clock genes' germline variants and the risk of developing cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate

  4. Automatic breast cancer risk assessment from digital mammograms

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Brandt, Sami; Karssemeijer, N

    Purpose: Textural characteristics of the breast tissue structure on mammogram have been shown to improve breast cancer risk assessment in several large studies. Currently, however, the texture is not used to assess risk in standard clinical procedures or involved in general breast cancer risk ass...

  5. Regular use of aspirin and pancreatic cancer risk

    Directory of Open Access Journals (Sweden)

    Mahoney Martin C

    2002-09-01

    Full Text Available Abstract Background Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs has been consistently associated with reduced risk of colorectal cancer and adenoma, and there is some evidence for a protective effect for other types of cancer. As experimental studies reveal a possible role for NSAIDs is reducing the risk of pancreatic cancer, epidemiological studies examining similar associations in human populations become more important. Methods In this hospital-based case-control study, 194 patients with pancreatic cancer were compared to 582 age and sex-matched patients with non-neoplastic conditions to examine the association between aspirin use and risk of pancreatic cancer. All participants received medical services at the Roswell Park Cancer Institute in Buffalo, NY and completed a comprehensive epidemiologic questionnaire that included information on demographics, lifestyle factors and medical history as well as frequency and duration of aspirin use. Patients using at least one tablet per week for at least six months were classified as regular aspirin users. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs with 95% confidence intervals (CIs. Results Pancreatic cancer risk in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95% CI 0.72–1.39. No significant change in risk was found in relation to greater frequency or prolonged duration of use, in the total sample or in either gender. Conclusions These data suggest that regular aspirin use may not be associated with lower risk of pancreatic cancer.

  6. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...... cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1...

  7. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  8. Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts.

    Science.gov (United States)

    Liu, Ying; Geng, Yue-Hang; Yang, Hui; Yang, Han; Zhou, Yan-Ting; Zhang, Hong-Quan; Tian, Xin-Xia; Fang, Wei-Gang

    2018-05-04

    Our previous work has demonstrated that extracellular ATP is an important pro-invasive factor, and in this study, we tapped into a possible mechanism involved. We discovered that ATP could upregulate both the intracellular expression and secretion of S100A4 in breast cancer cells and fibroblasts. Apart from stimulating breast cancer cell motility via intracellular S100A4, ATP enhanced the ability of breast cancer cells to transform fibroblasts into cancer-associated fibroblast (CAF)-like cells, which in turn secreted S100A4 to further promote cancer cell motility. Both apyrase and niclosamide treatments could inhibit metastasis of inoculated tumors to lung, liver and kidney in mice model, and CAFs from these treated tumors exhibited weakened migration-stimulating capacity for breast cancer cells. Collectively, our data indicate that extracellular ATP promotes the interactions between breast cancer cells and fibroblasts, which work collaboratively via production of S100A4 to exacerbate breast cancer metastasis. Copyright © 2018. Published by Elsevier B.V.

  9. Chemopreventive properties of raisins originating from Greece in colon cancer cells.

    Science.gov (United States)

    Kountouri, Aggeliki M; Gioxari, Aristea; Karvela, Evangelia; Kaliora, Andriana C; Karvelas, Michalis; Karathanos, Vaios T

    2013-02-26

    Colorectal cancer is one of the major causes of cancer-related mortality in humans in both developed and developing countries. Dietary patterns influence the risk of colon cancer development, while plant-derived foods have gained great interest, due to the high content of antioxidants. Corinthian raisins (Currants, CR) and Sultanas (S) (Vitis vinifera L., Vitaceae) are dried vine fruits produced in Greece with many culinary uses in both the Mediterranean and the Western nutrition. In the present study, we investigated the effects of CR and S on human colon cancer cells. Methanol extracts of CR and S were used at different concentrations. The total polyphenol content and anti-radical activity were measured by Folin-Ciocalteu and DPPH, respectively. Antioxidant, anti-inflammatory and anti-proliferative effects on HT29 cell culture were evaluated. All extracts exhibited DPPH˙ scavenging activity in a dose-dependent manner. Both products suppressed cell proliferation, while the levels of glutathione and cyclooxygenase 2 were significantly decreased. A significant reduction in IL-8 levels and NF-kappaB p65 activation was also observed. Both antioxidant and anti-inflammatory effects were dependent on the duration of exposure. Results indicate that the methanol extracts of CR and S exhibit anti-radical activity in vitro, as well as cancer preventive efficacy on colon cancer cells, with S having slightly higher activity. The beneficial properties of these unique dried grapes are attributed to their high content of phenolic compounds.

  10. Relationship of Predicted Risk of Developing Invasive Breast Cancer, as Assessed with Three Models, and Breast Cancer Mortality among Breast Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Mark E Sherman

    Full Text Available Breast cancer risk prediction models are used to plan clinical trials and counsel women; however, relationships of predicted risks of breast cancer incidence and prognosis after breast cancer diagnosis are unknown.Using largely pre-diagnostic information from the Breast Cancer Surveillance Consortium (BCSC for 37,939 invasive breast cancers (1996-2007, we estimated 5-year breast cancer risk (<1%; 1-1.66%; ≥1.67% with three models: BCSC 1-year risk model (BCSC-1; adapted to 5-year predictions; Breast Cancer Risk Assessment Tool (BCRAT; and BCSC 5-year risk model (BCSC-5. Breast cancer-specific mortality post-diagnosis (range: 1-13 years; median: 5.4-5.6 years was related to predicted risk of developing breast cancer using unadjusted Cox proportional hazards models, and in age-stratified (35-44; 45-54; 55-69; 70-89 years models adjusted for continuous age, BCSC registry, calendar period, income, mode of presentation, stage and treatment. Mean age at diagnosis was 60 years.Of 6,021 deaths, 2,993 (49.7% were ascribed to breast cancer. In unadjusted case-only analyses, predicted breast cancer risk ≥1.67% versus <1.0% was associated with lower risk of breast cancer death; BCSC-1: hazard ratio (HR = 0.82 (95% CI = 0.75-0.90; BCRAT: HR = 0.72 (95% CI = 0.65-0.81 and BCSC-5: HR = 0.84 (95% CI = 0.75-0.94. Age-stratified, adjusted models showed similar, although mostly non-significant HRs. Among women ages 55-69 years, HRs approximated 1.0. Generally, higher predicted risk was inversely related to percentages of cancers with unfavorable prognostic characteristics, especially among women 35-44 years.Among cases assessed with three models, higher predicted risk of developing breast cancer was not associated with greater risk of breast cancer death; thus, these models would have limited utility in planning studies to evaluate breast cancer mortality reduction strategies. Further, when offering women counseling, it may be useful to note that high

  11. Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells.

    Science.gov (United States)

    Gandhi, Nishant; Wild, Aaron T; Chettiar, Sivarajan T; Aziz, Khaled; Kato, Yoshinori; Gajula, Rajendra P; Williams, Russell D; Cades, Jessica A; Annadanam, Anvesh; Song, Danny; Zhang, Yonggang; Hales, Russell K; Herman, Joseph M; Armour, Elwood; DeWeese, Theodore L; Schaeffer, Edward M; Tran, Phuoc T

    2013-04-01

    Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the "non-oncogene" addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded "client" proteins, that is commonly overexpressed in tumor cells. Hsp90 client proteins include critical components of pathways implicated in prostate cancer cell survival and radioresistance, such as androgen receptor signaling and the PI3K-Akt-mTOR pathway. We examined the effects of a novel non-geldanamycin Hsp90 inhibitor, AUY922, combined with radiation (RT) on two prostate cancer cell lines, Myc-CaP and PC3, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γ-H2AX foci kinetics and client protein expression in pathways important for prostate cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined treatment (RT-AUY922) on the PI3K-Akt-mTOR and AR pathways in a hind-flank tumor graft model. We observed that AUY922 caused supra-additive radiosensitization in both cell lines at low nanomolar doses with enhancement ratios between 1.4-1.7 (p < 0.01). RT-AUY922 increased apoptotic cell death compared with either therapy alone, induced G 2-M arrest and produced marked changes in client protein expression. These results were confirmed in vivo, where RT-AUY922 combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in Myc-CaP and PC3 tumor grafts (both p < 0.0001). Our data suggest that combined RT-AUY922 therapy exhibits promising activity against prostate cancer cells, which should be investigated in clinical studies.

  12. The Prognostic Role of Circulating Tumor Cells (CTC) in High-risk Non-muscle-invasive Bladder Cancer.

    Science.gov (United States)

    Busetto, Gian Maria; Ferro, Matteo; Del Giudice, Francesco; Antonini, Gabriele; Chung, Benjamin I; Sperduti, Isabella; Giannarelli, Diana; Lucarelli, Giuseppe; Borghesi, Marco; Musi, Gennaro; de Cobelli, Ottavio; De Berardinis, Ettore

    2017-08-01

    The purpose of this study was to evaluate the impact of circulating tumor cells (CTCs) as a prognostic marker in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) and assess the efficacy and reliability of 2 different CTC isolation methods. Globally, 155 patients with a pathologically confirmed diagnosis of high-risk NMIBC were included (pT1G3 with or without carcinoma in situ) and underwent transurethral resection of bladder tumor (TURB) after a blood withdrawal for CTC evaluation. A total of 101 patients (Group A) had their samples analyzed with the CellSearch automated system, and 54 (Group B) had their samples analyzed with the CELLection Dynabeads manual system. Patients were followed for 28 months, and during this interval, there were a total of 65 (41.9%) recurrences, 27 (17.4%) disease progressions, and 9 (5.8%) lymph node and/or bone metastasis. In our CTC analysis, there were 20 (19.8%) positive patients in Group A and 24 in Group B (44.4%). In our analysis, we found a strong correlation between CTC presence and time to first recurrence; in Group A, we observed an incidence of recurrence in 75% of CTC-positive patients and in Group B of 83% of CTC-positive patients. The time to progression was also strongly correlated with CTCs: 65% and 29%, respectively, of those patients who progressed in those with CTCs in Group A and B. The study demonstrates the potential role of CTCs as a prognostic marker for risk stratification in patients with NMIBC, to predict both recurrence and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers

    Science.gov (United States)

    Finkelman, Brian S.; Rubinstein, Wendy S.; Friedman, Sue; Friebel, Tara M.; Dubitsky, Shera; Schonberger, Niecee Singer; Shoretz, Rochelle; Singer, Christian F.; Blum, Joanne L.; Tung, Nadine; Olopade, Olufunmilayo I.; Weitzel, Jeffrey N.; Lynch, Henry T.; Snyder, Carrie; Garber, Judy E.; Schildkraut, Joellen; Daly, Mary B.; Isaacs, Claudine; Pichert, Gabrielle; Neuhausen, Susan L.; Couch, Fergus J.; van't Veer, Laura; Eeles, Rosalind; Bancroft, Elizabeth; Evans, D. Gareth; Ganz, Patricia A.; Tomlinson, Gail E.; Narod, Steven A.; Matloff, Ellen; Domchek, Susan; Rebbeck, Timothy R.

    2012-01-01

    Purpose Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. Methods Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. Results Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. Conclusion Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care. PMID:22430266

  14. Marijuana use and increased risk of squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Zhang, Z F; Morgenstern, H; Spitz, M R; Tashkin, D P; Yu, G P; Marshall, J R; Hsu, T C; Schantz, S P

    1999-12-01

    Marijuana is the most commonly used illegal drug in the United States. In some subcultures, it is widely perceived to be harmless. Although the carcinogenic properties of marijuana smoke are similar to those of tobacco, no epidemiological studies of the relationship between marijuana use and head and neck cancer have been published. The relationship between marijuana use and head and neck cancer was investigated by a case-control study of 173 previously untreated cases with pathologically confirmed diagnoses of squamous cell carcinoma of the head and neck and 176 cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and 1994. Epidemiological data were collected by using a structured questionnaire, which included history of tobacco smoking, alcohol use, and marijuana use. The associations between marijuana use and head and neck cancer were analyzed by Mantel-Haenszel methods and logistic regression models. Controlling for age, sex, race, education, alcohol consumption, pack-years of cigarette smoking, and passive smoking, the risk of squamous cell carcinoma of the head and neck was increased with marijuana use [odds ratio (OR) comparing ever with never users, 2.6; 95% confidence interval (CI), 1.1-6.6]. Dose-response relationships were observed for frequency of marijuana use/day (P for trend marijuana use (P for trend marijuana use were observed with cigarette smoking, mutagen sensitivity, and to a lesser extent, alcohol use. Our results suggest that marijuana use may increase the risk of head and neck cancer with a strong dose-response pattern. Our analysis indicated that marijuana use may interact with mutagen sensitivity and other risk factors to increase the risk of head and neck cancer. The results need to be interpreted with some caution in drawing causal inferences because of certain methodological limitations, especially with regard to interactions.

  15. Use of mobile phones and cancer risk.

    Science.gov (United States)

    Ayanda, Olushola S; Baba, Alafara A; Ayanda, Omolola T

    2012-01-01

    Mobile phones work by transmitting and receiving radio frequency microwave radiation. The radio frequency (RF) emitted by mobile phones is stronger than FM radio signal which are known to cause cancer. Though research and evidence available on the risk of cancer by mobile phones does not provide a clear and direct support that mobile phones cause cancers. Evidence does not also support an association between exposure to radio frequency and microwave radiation from mobile phones and direct effects on health. It is however clear that lack of available evidence of cancer as regards the use of mobile phone should not be interpreted as proof of absence of cancer risk, so that excessive use of mobile phones should be taken very seriously and with caution to prevent cancer.

  16. CD44 and SSEA-4 positive cells in an oral cancer cell line HSC-4 possess cancer stem-like cell characteristics.

    Science.gov (United States)

    Noto, Zenko; Yoshida, Toshiko; Okabe, Motonori; Koike, Chika; Fathy, Moustafa; Tsuno, Hiroaki; Tomihara, Kei; Arai, Naoya; Noguchi, Makoto; Nikaido, Toshio

    2013-08-01

    Cancer may be derived from cancer stem-like cells (CSCs), which are tumor-initiating cells that have properties similar to those of stem cells. Identification and isolation of CSCs needs to be improved further. CSCs markers were examined in human oral cancer cell lines by flow cytometry. The stem cell properties of subpopulations expressing different markers were assessed further by in vitro sphere formation assays, expression of stemness genes, drug resistance assays, and the ability to form tumors in nude mice. We demonstrated that CSCs could be isolated by the cell surface markers CD44 and stage-specific embryonic antigen-4 (SSEA-4). CD44+SSEA-4+ cells exhibited cancer stem-like properties, including extensive self-renewal into the bulk of cancer cells. In vivo xenograft experiments indicated that CD44+SSEA-4+ cells exhibit the highest tumorigenic capacity compared with the remaining subpopulations and parental cells. Double-positive cells for CD44 and SSEA-4 exhibited preferential expression of some stemness genes and were more resistant to the anticancer drugs, cisplatin and 5-fluorouracil (5-FU). In addition, cells expressing CD44 and SSEA-4 were detected in all tumor specimens analyzed, while coexpression of CD44 and SSEA-4 was not detectable in normal oral mucosa. Our findings suggest that CD44+SSEA-4+ cells exhibit the characteristics of CSCs in oral squamous cell carcinoma and provide a target for the development of more effective therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Cognitive and affective influences on perceived risk of ovarian cancer.

    Science.gov (United States)

    Peipins, Lucy A; McCarty, Frances; Hawkins, Nikki A; Rodriguez, Juan L; Scholl, Lawrence E; Leadbetter, Steven

    2015-03-01

    Studies suggest that both affective and cognitive processes are involved in the perception of vulnerability to cancer and that affect has an early influence in this assessment of risk. We constructed a path model based on a conceptual framework of heuristic reasoning (affect, resemblance, and availability) coupled with cognitive processes involved in developing personal models of cancer causation. From an eligible cohort of 16 700 women in a managed care organization, we randomly selected 2524 women at high, elevated, and average risk of ovarian cancer and administered a questionnaire to test our model (response rate 76.3%). Path analysis delineated the relationships between personal and cognitive characteristics (number of relatives with cancer, age, ideas about cancer causation, perceived resemblance to an affected friend or relative, and ovarian cancer knowledge) and emotional constructs (closeness to an affected relative or friend, time spent processing the cancer experience, and cancer worry) on perceived risk of ovarian cancer. Our final model fit the data well (root mean square error of approximation (RMSEA) = 0.028, comparative fit index (CFI) = 0.99, normed fit index (NFI) = 0.98). This final model (1) demonstrated the nature and direction of relationships between cognitive characteristics and perceived risk; (2) showed that time spent processing the cancer experience was associated with cancer worry; and (3) showed that cancer worry moderately influenced perceived risk. Our results highlight the important role that family cancer experience has on cancer worry and shows how cancer experience translates into personal risk perceptions. This understanding informs the discordance between medical or objective risk assessment and personal risk assessment. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.

  18. Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Fabien J Cousin

    Full Text Available Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate.A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy.Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.

  19. Awareness of endometrial cancer risk and compliance with screening in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Mosgaard, Berit J; Gerdes, Anne-Marie

    2012-01-01

    Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors...

  20. History of Severe Sunburn and Risk of Skin Cancer Among Women and Men in 2 Prospective Cohort Studies.

    Science.gov (United States)

    Wu, Shaowei; Cho, Eunyoung; Li, Wen-Qing; Weinstock, Martin A; Han, Jiali; Qureshi, Abrar A

    2016-05-01

    Few studies have assessed the relationship between sunburn and risk of different skin cancers (melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC)) in prospective studies simultaneously, and little is known about the association of severe sunburns at different body sites with skin cancer risk. We used data on 87,166 women in the Nurses' Health Study (1982-2010) and 32,959 men in the Health Professionals Follow-up Study (1992-2010) to investigate skin cancer risk associated with history of severe sunburns at different body sites (face/arms, trunk, and lower limbs). After adjustment for other risk factors, overall baseline history of severe sunburn was more apparently associated with risk of melanoma than with risk of SCC and BCC in men (multivariable-adjusted hazard ratios were 2.41 (95% confidence interval (CI): 1.32, 4.41) for melanoma, 1.48 (95% CI: 1.08, 2.03) for SCC, and 1.18 (95% CI: 1.06, 1.32) for BCC) but not in women. Sunburn on the trunk appeared to be more closely associated with melanoma risk, but not risk of SCC and BCC, when compared with sunburns at other body sites (face/arms and lower limbs). These differences were more apparent in men than in women. Pending further investigation, our findings add novel insights to the existing literature on sunburn history and skin cancer risk. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.