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Sample records for breast-ovarian cancer families

  1. Risk perception and cancer worries in families at increased risk of familial breast/ovarian cancer

    OpenAIRE

    Mellon, Suzanne; Gold, Robin; Janisse, James; Cichon, Michelle; Tainsky, Michael A; Simon, Michael S.; Korczak, Jeannette

    2008-01-01

    While families at increased risk for familial breast/ovarian cancer continue to overestimate their cancer risk with increased cancer worries about the future, few studies have examined factors that affect inherited cancer risk perception and cancer worries in both survivors and unaffected female relatives. The purpose of this study was to examine variables that may affect cancer worries and risk perceptions from a family-based perspective in a racially diverse, community-based, random sample ...

  2. BRCA1 and BRCA2 Unclassified Variants and Missense Polymorphisms in Algerian Breast/Ovarian Cancer Families

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    Farid Cherbal

    2012-01-01

    Full Text Available Background: BRCA1 and BRCA2 germline mutations predispose heterozygous carriers to hereditary breast/ovarian cancer. However, unclassified variants (UVs (variants with unknown clinical significance and missense polymorphisms in BRCA1 and BRCA2 genes pose a problem in genetic counseling, as their impact on risk of breast and ovarian cancer is still unclear. The objective of our study was to identify UVs and missense polymorphisms in Algerian breast/ovarian cancer patients and relatives tested previously for BRCA1 and BRCA2 genes germline mutations analysis.

  3. Genetic testing and familial implications in breast-ovarian cancer families

    NARCIS (Netherlands)

    Oosterwijk, Jan C; de Vries, Jakob; Mourits, Marian J; de Bock, Geertruida H

    2014-01-01

    DNA-testing for BRCA1 and BRCA2 has become incorporated in the diagnostic procedure of patients with breast and/or ovarian cancer. Since 1994 an immense amount of information has been gathered on mutation spectra, mutation risk assessment, cancer risks for mutation carriers, factors that modify thes

  4. Towards Evidence-Based Management of Inherited Breast and Breast-Ovarian Cancer

    OpenAIRE

    Møller Pål

    2004-01-01

    Abstract Inherited breast-ovarian cancer was described in 1866. The underlying genetic defects in BRCA1/2 were demonstrated 128 years later. We now have 10 years of experience with genetic testing in BRCA kindreds. The majority of breast cancer kindreds (familial breast cancer) do not demonstrate ovarian cancer and are not associated with BRCA mutations. The effect of early diagnosis and treatment is monitored through international collaborations. BRCA1-associated breast cancer is biologicall...

  5. Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families

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    Pichette Roxane

    2006-09-01

    Full Text Available Abstract Background Ataxia telangiectasia-mutated and Rad3-related (ATR is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. Methods ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD, haplotype analyses, and tagging SNP (tSNP identification. Expression analyses were carried out using real-time PCR. Results The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. Conclusion Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association

  6. Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families

    International Nuclear Information System (INIS)

    Ataxia telangiectasia-mutated and Rad3-related (ATR) is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD), haplotype analyses, and tagging SNP (tSNP) identification. Expression analyses were carried out using real-time PCR. The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association studies. In addition, our study led to the characterization of a

  7. Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population

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    Abdelilah Laraqui, Nancy Uhrhammer, Idriss Lahlou-Amine, Hicham EL Rhaffouli, Jamila El Baghdadi, Mohamed Dehayni, Rahali Driss Moussaoui, Mohamed Ichou, Yassir Sbitti, Abderrahman Al Bouzidi, Said Amzazi, Yves-Jean Bignon

    2013-01-01

    Full Text Available Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for BRCA testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the BRCA1 gene. 31.6 % (6/19 of familial cases and 1 % (1/102 of early-onset sporadic (< 45 years were found to be associated with BRCA1 mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA, one missense mutation (c.5095C>T, and one nonsense mutation (c.4942A>T. The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in BRCA1, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55, but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of BRCA2 in BC is also under study.

  8. Genetic counseling does not fulfill the counselees' need for certainty in hereditary breast/ovarian cancer families : an explorative assessment

    NARCIS (Netherlands)

    Vos, Joel; Menko, Fred H.; Oosterwijk, Jan C.; van Asperen, Christi J.; Stiggelbout, Anne M.; Tibben, Aad

    2013-01-01

    Background Many cancer-patients undergo DNA testing in the BRCA1/2 genes to receive information about the likelihood that cancer is heritable. Previous nonsystematic studies suggested that DNA testing often does not fulfill the counselees' needs for certainty. We explored the balance between the cou

  9. Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

    DEFF Research Database (Denmark)

    Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders;

    2009-01-01

    BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovarian...

  10. Identification of a Danish breast/ovarian cancer family double heterozygote for BRCA1 and BRCA2 mutations

    DEFF Research Database (Denmark)

    Steffensen, Ane Y; Jønson, Lars; Ejlertsen, Bent;

    2010-01-01

    (RT)-PCR analysis revealed that the BRCA2 mutation results in skipping of exon 7, thereby introducing a frameshift and a premature stop codon. We therefore classify the mutation as disease causing. Since the BRCA1 Arg1699Gln mutation is also suggested to be disease-causing, we consider this family...

  11. BRCA1 1675delA and 1135insA Account for One Third of Norwegian Familial Breast-Ovarian Cancer and Are Associated with Later Disease Onset than Less Frequent Mutations

    Directory of Open Access Journals (Sweden)

    Åke Borg

    1999-01-01

    Full Text Available A total of 845 women from breast-ovarian cancer kindreds were enrolled in a clinical follow-up program for early disease diagnosis; 35 women were prospectively identified with cancer. In order to estimate the role of genetic factors for cancer predisposition in this well-defined set of patients, considered as representative for familial breast-ovarian cancer in the Norwegian population, the BRCA1 gene was investigated for germline mutations. The entire coding region of BRCA1 was analysed using a protein truncation test, direct sequencing and a screen for known large genomic deletions and insertions. Twenty one (60% of the 35 patients were identified as carriers of 11 distinct BRCA1 mutations. Two previously described founder mutations, 1675delA and 1135insA, were found to account for more than half (11/21 of all BRCA1 cases and for almost one third (11/35 of all breast and ovarian cancers. Supported by a previous population-based analysis of these founder mutations in ovarian cancer, our findings suggest that a significant proportion of women at risk for developing inherited breast and ovarian cancer can be identified. This is particularly obvious in certain geographic regions where these founder mutations are prevalent. Women carrying the two founder mutations had a significantly older age of disease onset as compared to women with other BRCA1 mutations. This observation indicates that BRCA mutation penetrance estimates from populations with strong founder effects may be biased. One reason why some deleterious mutations are allowed to prevail in a population may be coupled to penetrance and the fact that they seldom induce disease in women in child-bearing ages. Eleven out of 12 (92% breast cancers in BRCA1 mutation carriers were estrogen receptor negative, versus 4 out of 9 (44% in mutation negative patients (p = 0.03. Histopathological characteristics of the prospectively detected cancers indicated an unfavourable prognosis in mutation

  12. Advocate's Viewpoint on Hereditary Breast/Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Kolling-Dandrieu Francisca

    2004-08-01

    Full Text Available Abstract This paper discusses the presentation I held at the symposium on genetics during the 4th European Breast Cancer Conference held in Hamburg in March 2004. Primarily, the goals and working methods of the advocacy group specialised in Hereditary Breast/Ovarian Cancer of the Dutch Breast Cancer Patient Organisation known as BorstkankerVereniging Nederland (BVN are explained. Furthermore, some specific individual problems that mutation carriers might encounter before and after BRCA1/2 susceptibility testing are discussed. These include: dilemmas in choosing preventive interventions, dealing with the psychological impact of knowing you are a mutation carrier, dealing with the social implications of being genetically at risk, an example of insurance discrimination. In addition, some controversial social and ethical issues that are currently under debate are highlighted, such as the issue of the European patenting of the breast cancer susceptibility genes BRCA1 and BRCA2. Since this topic could also become relevant for other gene-related diseases, society as a whole has to consider the ethical and social implications related to the patenting of human genes in general. Another ethical area of debate is the controversial issue of prenatal BRCA testing and the choice of pregnancy termination. Finally, the Working Party pleads for the international co-operation and exchange of data and experience among professionals as well as patients. It appears that professionals in different European countries tend to advise on different risk management strategies and treatments and as such, the Working Party strongly advocates the international standardisation of risk management and treatment of mutation carriers. In this respect, specific attention should be given to a group that has had a non-informative or negative BRCA test result, because this group is still considered to be at high risk to develop the disease.

  13. Hereditary breast/ovarian cancer: clinicopathological characteristics and survival of BRCA2 positive and negative cases.

    Science.gov (United States)

    Syamala, Vani; Syamala, Volga S; Sreeja, Leelakumari; Raveendran, Praveenkumar B; Vijayalekshmi, R V; Sheeja, V R; Santhi, S; Kuttan, Ratheesan; Abraham, Elizabeth K; Ankathil, Ravindran

    2008-01-01

    The clinical and pathological characteristics and prognostic outcome of patients with hereditary breast/ovarian cancer and BRCA2 mutations are poorly known. Hence, the present study aimed to correlate the BRCA2 mutation status with clinical characteristics and overall survival of 102 breast/ovarian cancer patients in Kerala, South India. All the coding regions of BRCA2 genes were PCR amplified and analyzed for mutations employing Conformation Sensitive Gel Electrophoresis and characterized by sequencing. The ORs with 95% Cls was computed to assess the association between BRCA2 gene mutation status and clinicopathologic characteristics of breast cancer patients. Survival curves were generated according to Kaplan-Meier method using Log Rank test and Cox proportional hazards regression method. Out of the 102 breast/ovarian cancer patients with known BRCA2 status, 19 were BRCA2 mutation positive. In survival analysis, BRCA2 gene mutation status (P = 0.02) and clinicopathologic parameters such as tumour size (p = 0.01), metastasis (P = 0.01), disease stage (P = 0.03) and laterality (P = 0.02) were significantly associated with poor prognosis of breast cancer patients. Patients with hereditary breast/ovarian cancer resulting from a BRCA2 mutation have been conclusively shown to have a worse survival prognosis compared to the non mutated group of patients. PMID:19066131

  14. Women’s Satisfaction with Genetic Counseling for Hereditary Breast-Ovarian Cancer: Psychological Aspects

    OpenAIRE

    Tercyak, Kenneth P.; DeMarco, Tiffani A.; Mars, Bryn D.; Peshkin, Beth N.

    2004-01-01

    Women who participate in BRCA1/2 cancer genetic counseling do so for a variety of reasons, including learning quantitative risk information about their chances of developing hereditary breast-ovarian cancer at some point during their lifetimes. For these women, obtaining pre-test and disclosure genetic counseling with a professional affords them numerous potential benefits, including adequate preparation for, and accurate interpretation of, their test results. In consequence, women commonly r...

  15. First application of next-generation sequencing in Moroccan breast/ovarian cancer families and report of a novel frameshift mutation of the BRCA1 gene

    Science.gov (United States)

    Jouali, Farah; Laarabi, Fatima-Zahra; Marchoudi, Nabila; Ratbi, Ilham; Elalaoui, Siham Chafai; Rhaissi, Houria; Fekkak, Jamal; Sefiani, Abdelaziz

    2016-01-01

    At present, breast cancer is the most common type of cancer in females. The majority of cases are sporadic, but 5–10% are due to an inherited predisposition to develop breast and ovarian cancers, which are transmitted as an autosomal dominant form with incomplete penetrance. The beneficial effects of clinical genetic testing, including next generation sequencing (NGS) for BRCA1/2 mutations, is major; in particular, it benefits the care of patients and the counseling of relatives that are at risk of breast cancer, in order to reduce breast cancer mortality. BRCA genetic testing was performed in 15 patients with breast cancer and a family with positivity for the heterozygous c.6428C>A mutation of the BRCA2 gene. Informed consent was obtained from all the subjects. Genomic DNAs were extracted and the NGS for genes was performed using the Ion Torrent Personal Genome Machine (PGM) with a 316 chip. The reads were aligned with the human reference HG19 genome to elucidate variants in the BRCA1 and BRCA2 genes. Mutations detected by the PGM platform were confirmed by target direct Sanger sequencing on a second patient DNA sample. In total, 4 BRCA variants were identified in 6 families by NGS. Of these, 3 mutations had been previously reported: c.2126insA of BRCA1, and c.1310_1313delAAGA and c.7235insG of BRCA2. The fourth variant, c.3453delT in BRCA1, has, to the best of our knowledge, never been previously reported. The present study is the first to apply NGS of the BRCA1 and BRCA2 genes to a Moroccan population, prompting additional investigation into local founder mutations and variant characteristics in the region. The variants with no clear clinical significance may present a diagnostic challenge when performing targeted resequencing. These results confirm that an NGS approach based on Ampliseq libraries and PGM sequencing is a highly efficient, speedy and high-throughput mutation detection method, which may be preferable in lower income countries.

  16. Müllerian intra-abdominal carcinomatosis in hereditary breast ovarian cancer syndrome: implications for risk-reducing surgery.

    Science.gov (United States)

    Casey, Murray Joseph; Colanta, Agnes B

    2016-07-01

    More than 40 years ago Lynch et al. described several multigenerational breast cancer family pedigrees which demonstrated autosomal dominant inheritance of a trait(s) that increased risks for both breast and ovarian cancers. Mutation carriers in at least 90 % of these hereditary breast ovarian cancer (HBOC) syndrome families have been linked to cancer-associated mutations in the genes BRCA1 and BRCA2. This review focuses on the contributions of Lynch, colleagues and collaborators and pertinent literature, toward defining the HBOC syndrome, the cancer risks that the inherited adverse mutations convey, the gynecologic tissues and organs from which the malignancy may arise to disseminate throughout the pelvic and abdominal organs and peritoneum and how this information can be used to reduce the risk and morbidities of intra-abdominal carcinomatosis in effected individuals. PMID:26875157

  17. Linkage analysis of 19 French breast cancer families, with five chromosome 17q markers.

    OpenAIRE

    Mazoyer, S.; Lalle, P.; Narod, S A; Bignon, Y J; Courjal, F.; Jamot, B; Dutrillaux, B; Stoppa-Lyonnett, D; Sobol, H

    1993-01-01

    Nineteen French breast and breast-ovarian cancer families were tested for linkage with five chromosome 17q markers. The five breast-ovarian cancer families as a group give positive evidence for linkage, whereas the 14 breast cancer-only families do not. Heterogeneity of linkage of breast and breast-ovarian cancers is significant in France and supports the existence of more than one susceptibility gene.

  18. Coordinated prophylactic surgical management for women with hereditary breast-ovarian cancer syndrome

    Directory of Open Access Journals (Sweden)

    Bodurka Diane C

    2008-04-01

    Full Text Available Abstract Background Women with BRCA1 or BRCA2 mutations have a substantially increased risk of breast and ovarian cancer compared with the general population. Therefore, prophylactic mastectomy (PM and bilateral salpingo-oophorectomy (BSO have been proposed as risk-reduction strategies for BRCA1/2 mutation carriers. We aimed to assess the feasibility of coordinated PM and BSO in hereditary breast-ovarian cancer syndrome. Methods High risk women for breast and ovarian cancer who underwent coordinated PM and BSO were included in this study. Clinical characteristics and surgical and oncologic outcomes were retrospectively reviewed. Results Twelve patients underwent coordinated PM and BSO. Ten had history of previous breast cancer. Autologous breast reconstruction was performed in ten patients. The mean age at surgery was 43 (range 34–65. Mean operating time was 9.3 hours (range 3–16 with a mean postoperative hospitalization of 5.4 days (range 4–8. Intraoperatively, there were no major surgical complications. Postoperatively, one patient developed an abdominal wound dehiscence, another reoperation for flap congestion; one had umbilical superficial epidermolysis, and one patient developed aspiration pneumonia. At a mean follow-up of 84 months, 10 of patients were cancer-free. Although no patients developed a new primary cancer, two developed a distant recurrence. Conclusion Coordinated PM and BSO is a feasible procedure with acceptable morbidity in selected high-risk patients that desire to undergo surgery at one operative setting.

  19. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

    DEFF Research Database (Denmark)

    Kar, Siddhartha P; Beesley, Jonathan; Amin Al Olama, Ali;

    2016-01-01

    UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349...

  20. Evolution of the colored eco-genetic relationship map (CEGRM) for assessing social functioning in women in hereditary breast-ovarian (HBOC) families.

    Science.gov (United States)

    Peters, June A; Hoskins, Lindsey; Prindiville, Sheila; Kenen, Regina; Greene, Mark H

    2006-12-01

    The CEGRM was initially conceived as a simple, concise, visual representation of the social interaction domains of information, tangible services and emotional exchanges (Kenen, R., & Peters, J. (2001). J Genet Counsel, 10, 289-309). A blend of the genetic pedigree, genogram, and ecomap, the CEGRM was developed to facilitate contemporary genetic counseling goals. An exploratory pilot study of 20 subjects showed that it was feasible, comfortable and efficiently accomplished, and that the process was useful both for assessment and as an intervention with study participants (Peters, J. A., Kenen, R., Giusti, R., Loud, J., Weissman, N., & Greene, M. H. (2004). Am J Med Genet Part A, 130A, 258-264). Subsequently, we have extended the CEGRM to 150 women from hereditary breast/ovarian cancer (HBOC) families; three different investigators have successfully administered this tool. The preliminary findings from the exploratory study were confirmed in the larger sample. Engaging in the interactive, insight-promoting CEGRM process provides a novel tool for assessing the social context of genetic testing, and helping high-risk women better understand and integrate genetic information into their personal and family identities, health beliefs, and decisions. PMID:17111216

  1. Familial pancreatic cancer.

    Science.gov (United States)

    Klein, A P; Hruban, R H; Brune, K A; Petersen, G M; Goggins, M

    2001-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States and will be responsible for an estimated 28,900 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a family history of the disease. A small fraction of this aggregation can be accounted for in inherited cancer syndromes, including familial atypical multiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian cancer, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, pl6 (familial atypical multiple-mole melanoma), mismatch repair (hereditary nonpolyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with apparently sporadic pancreatic cancer. Many patients with pancreatic cancers caused by a germline mutation in a cancer-causing gene do not have a pedigree that is suggestive of a familial cancer syndrome. A recent prospective analysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multiple first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians target screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.

  2. The human insulin-like growth factor-binding protein 4 gene maps to chromosome region 17q12-q21. 1 and is close to the gene for hereditary breast-ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tonin, P.; Vivier, A.; Morgan, K.; Narod, S.; Pollack, M. (McGill Univ., Montreal (Canada)); Ehrenborg, E.; Zazzi, H.; Luthman, H.; Larsson, C. (Karolinska Hospital, Stockholm (Sweden)); Lenoir, G. (International Agency for Research on Cancer, Lyon (France)) (and others)

    1993-11-01

    The gene for insulin-like growth factor-binding protein 4 (IGFBP4) codes for a serum protein that binds to the family of insulin-like growth factors and modulates their activity. It has been mapped by in situ hybridization to chromosome region 17q12-q21.1. The authors have developed a CA-repeat polymorphism from a cosmid clone containing IGFBP4. By linkage analysis, IGFBP4 maps to the chromosome 17q interval THRA1-D17S579. This interval also contains the gene for hereditary breast-ovarian cancer, BRCA1. Genetic recombination between IGFBP4 and BRCA1 places IGFBP4 centromeric to the cancer susceptibility gene and effectively excludes it as a candidate gene for BRCA1. IGFBP4 is, however, one of the closest known centromeric markers for BRCA1; the estimated recombination fraction is 0.015. IGFBP4 and D17S579 together define a 2.8-cM interval that contains BRCA1. 18 refs., 3 figs., 1 tab.

  3. BRCA1 and BRCA2 mutations in Danish families with hereditary breast and/or ovarian cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Hansen, Thomas V O; Borg, Ake;

    2008-01-01

    A national study of BRCA1 and BRCA2 mutations in Danish HBOC (Hereditary Breast Ovarian Cancer) families revealed a total number of 322 mutation positive families, 206 (64%) BRCA1 and 116 (36%) BRCA2 positive families from a population of 5.5 million inhabitants. Seven hundred and twenty six muta...

  4. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen;

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-n...

  5. Understanding emotional responses to breast/ovarian cancer genetic risk assessment: an applied test of a cognitive theory of emotion.

    Science.gov (United States)

    Phelps, Ceri; Bennett, Paul; Brain, Kate

    2008-10-01

    This study explored whether Smith and Lazarus' (1990, 1993) cognitive theory of emotion could predict emotional responses to an emotionally ambiguous real-life situation. Questionnaire data were collected from 145 women upon referral for cancer genetic risk assessment. These indicated a mixed emotional reaction of both positive and negative emotions to the assessment. Hierarchical regression analyses revealed that the hypothesised models explained between 20% and 33% of the variance of anxiety, hope and gratitude scores, but only 10% of the variance for challenge scores. For the previously unmodelled emotion of relief, 31% of the variance was explained by appraisals and core relational themes. The findings help explain why emotional responses to cancer genetic risk assessment vary and suggest that improving the accuracy of individuals' beliefs and expectations about the assessment process may help subsequent adaptation to risk information.

  6. Understanding emotional responses to breast/ovarian cancer genetic risk assessment: an applied test of a cognitive theory of emotion.

    Science.gov (United States)

    Phelps, Ceri; Bennett, Paul; Brain, Kate

    2008-10-01

    This study explored whether Smith and Lazarus' (1990, 1993) cognitive theory of emotion could predict emotional responses to an emotionally ambiguous real-life situation. Questionnaire data were collected from 145 women upon referral for cancer genetic risk assessment. These indicated a mixed emotional reaction of both positive and negative emotions to the assessment. Hierarchical regression analyses revealed that the hypothesised models explained between 20% and 33% of the variance of anxiety, hope and gratitude scores, but only 10% of the variance for challenge scores. For the previously unmodelled emotion of relief, 31% of the variance was explained by appraisals and core relational themes. The findings help explain why emotional responses to cancer genetic risk assessment vary and suggest that improving the accuracy of individuals' beliefs and expectations about the assessment process may help subsequent adaptation to risk information. PMID:18942008

  7. Analysis of Founder Mutations in Rare Tumors Associated With Hereditary Breast/Ovarian Cancer Reveals a Novel Association of BRCA2 Mutations with Ampulla of Vater Carcinomas.

    Science.gov (United States)

    Pinto, Pedro; Peixoto, Ana; Santos, Catarina; Rocha, Patrícia; Pinto, Carla; Pinheiro, Manuela; Leça, Luís; Martins, Ana Teresa; Ferreira, Verónica; Bartosch, Carla; Teixeira, Manuel R

    2016-01-01

    BRCA1 and BRCA2 mutations are responsible for hereditary breast and ovarian cancer, but they also confer an increased risk for the development of rarer cancers associated with this syndrome, namely, cancer of the pancreas, male breast, peritoneum, and fallopian tube. The objective of this work was to quantify the contribution of the founder mutations BRCA2 c.156_157insAlu and BRCA1 c.3331_3334del for cancer etiology in unselected hospital-based cohorts of Portuguese patients diagnosed with these rarer cancers, by using a strategy that included testing of archival tumor tissue. A total of 102 male breast, 68 pancreatic and 33 peritoneal/fallopian tube carcinoma cases were included in the study. The BRCA2 c.156_157insAlu mutation was observed with a frequency of 7.8% in male breast cancers, 3.0% in peritoneal/fallopian tube cancers, and 1.6% in pancreatic cancers, with estimated total contributions of germline BRCA2 mutations of 14.3%, 5.5%, and 2.8%, respectively. No carriers of the BRCA1 c.3331_3334del mutation were identified. During our study, a patient with an ampulla of Vater carcinoma was incidentally found to carry the BRCA2 c.156_157insAlu mutation, so we decided to test a consecutive series of additional 15 ampullary carcinomas for BRCA1/BRCA2 mutations using a combination of direct founder mutation testing and full gene analysis with next generation sequencing. BRCA2 mutations were observed with a frequency of 14.3% in ampulla of Vater carcinomas. In conclusion, taking into account the implications for both the individuals and their family members, we recommend that patients with these neoplasias should be offered BRCA1/BRCA2 genetic testing and we here show that it is feasible to test for founder mutations in archival tumor tissue. Furthermore, we identified for the first time a high frequency of germline BRCA2 mutations in ampullary cancers. PMID:27532258

  8. Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

    DEFF Research Database (Denmark)

    Burford, B; Gentry-Maharaj, A; Graham, R;

    2013-01-01

    Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed...... these autoantibodies in large population cohorts of sera taken before cancer diagnosis....

  9. Toxicity-adjusted dose (TAD) administration of chemotherapy: Effect of baseline and nadir neutrophil count in patients with breast, ovarian, and lung cancer?

    DEFF Research Database (Denmark)

    Carus, Andreas; Donskov, Frede; Gebski, Val;

    2011-01-01

    .I-IV, non-small cell lung cancer (NSCLC) st.II-IV, and small-cell lung cancer (SCLC) treated from 1997 to 2005 at Westmead Hospital, Sydney, with complete medical records of the first 3 cycles of chemotherapy and a full set of baseline and nadir laboratory data were collected from patient medical files.......Survival data were updated 2010. Results: A total of 819 patients were identified, comprising 507 patients with breast cancer, 118 patients with ovarian cancer, 115 patients with NSCLC and 79 patients with SCLC. Median survival for ovarian cancer patients obtaining nadir neutropenia below 2.0 x 109/l was 56...

  10. De novo recurrent germline mutation of the BRCA2 gene in a patient with early onset breast cancer

    OpenAIRE

    van der Luijt, R. B.; van Zon, P. H A; Jansen, R.; van der Sijs-Bos, C. J M; Warlam-Rodenhuis, C.; Ausems, M.

    2001-01-01

    Germline mutations in either of the two major breast cancer predisposition genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast/ovarian cancer. Identification of breast cancer patients carrying mutations of these genes is primarily based on a positive family history of breast/ovarian cancer or early onset of the disease or both. In the course of mutation screening of the BRCA1 and BRCA2 genes in a hospital based series of patients with risk factors for hereditary ...

  11. Familial breast cancer.

    OpenAIRE

    Phipps, R. F.; Perry, P M

    1988-01-01

    Familial breast cancer is important because of all the known risk factors associated with developing the disease. The one with the most predictability is a positive family history. It is also important because a family history causes anxiety in the families concerned, and young women will often ask their chance of developing the disease. This form of breast cancer accounts for 10% of causes and has factors that distinguish it from the sporadic variety. Relatives of familial breast cancer pati...

  12. Psychological and Behavioral Aspects of Receiving Genetic Counseling for Hereditary Cancer

    OpenAIRE

    Hayat Roshanai, Afsaneh

    2010-01-01

    The overall aims of this thesis were to investigate psychological and behavioral effects of receiving cancer genetic counseling for breast, ovarian and colorectal cancer and/or with a family history of these cancer types and to determine whether counselees’ informational needs were met. Study I was performed 3-7 years post-counseling. Participants (n=214) reported a relatively high level of anxiety but a low level of depression compared to cancer patients in general. However, there was no ind...

  13. Mutation analysis of BRCA1 and BRCA2 in a male breast cancer population

    Energy Technology Data Exchange (ETDEWEB)

    Friedman, L.S.; Gayther, S.A.; Ponder, B.A.J. [Univ. of Cambridge (United Kingdom)] [and others

    1997-02-01

    A population-based series of 54 male breast cancer cases from Southern California were analyzed for germ-line mutations in the inherited breast/ovarian cancer genes, BRCA1 and BRCA2. Nine (17%) of the patients had a family history of breast and/or ovarian cancer in at least one first-degree relative. A further seven (13%) of the patients reported breast/ovarian cancer in at least one second-degree relative and in no first-degree relatives. No germ-line BRCA1 mutations were found. Two male breast cancer patients (4% of the total) were found to carry novel truncating mutations in the BRCA2 gene. Only one of the two male breast cancer patients carrying a BRCA2 mutation had a family history of cancer, with one case of ovarian cancer in a first-degree relative. The remaining eight cases (89%) of male breast cancer with a family history of breast/ovarian cancer in first-degree relatives remain unaccounted for by mutations in either the BRCA1 gene or the BRCA2 gene. 23 refs., 1 fig., 5 tabs.

  14. Linking Genetic Counseling Content to Short-Term Outcomes in Individuals at Elevated Breast Cancer Risk

    OpenAIRE

    Kelly, Kimberly M.; Ellington, Lee; Schoenberg, Nancy; Agarwal, Parul; Jackson, Thomas; Dickinson, Stephanie; Abraham, Jame; Paskett, Electra D.; Leventhal, Howard; Andrykowski, Michael

    2014-01-01

    Few studies have linked actual genetic counseling content to short-term outcomes. Using the Self-regulation Model, the impact of cognitive and affective content in genetic counseling on short-term outcomes was studied in individuals at elevated risk of familial breast-ovarian cancer. Surveys assessed dependent variables: distress, perceived risk, and 6 knowledge measures (Meaning of Positive Test; Meaning of Negative Test; Personal Behavior; Practitioner Knowledge; Mechanisms of Cancer Inheri...

  15. Familial gastric cancer

    Directory of Open Access Journals (Sweden)

    Bresciani Cláudio

    2003-01-01

    Full Text Available BACKGROUND: Familial aggregation of gastric cancer has pointed out to a possible hereditary and genetic factor involved in the carcinogenesis of this disease. The diffuse type gastric cancer patients are frequently younger and the tumor has locally infiltrative growth pattern early in its development. Observation of families with frequent early onset gastric cancer has led to the identification of a novel gene implicated in gastric cancer susceptibility: CDH1/E-cadherin. Diffuse familiar gastric cancer is defined as any family presenting: two first-degree relatives with diffuse gastric cancer, one of them with age under 50 years or at least 3 first-degree relatives irrespective age of onset. CASE REPORT: The family reported by us does not fit in any of the classification proposed. The precise identification of these families by clinical and molecular tools is of great importance. The case reported is an example of a family that probably is a form of hereditary gastric cancer not yet fully understood. CONCLUSION: Soon there will be new criteria, possibly including genetic and molecular characteristics.

  16. Familial Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Stephen J. Lanspa

    2010-11-01

    Full Text Available Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer.

  17. Five recurrent BRCA1/2 mutations are responsible for cancer predisposition in the majority of Slovenian breast cancer families

    Directory of Open Access Journals (Sweden)

    Novakovic Srdjan

    2008-09-01

    Full Text Available Abstract Background Both recurrent and population specific mutations have been found in different areas of the world and more specifically in ethnically defined or isolated populations. The population of Slovenia has over several centuries undergone limited mixing with surrounding populations. The current study was aimed at establishing the mutation spectrum of BRCA1/2 in the Slovenian breast/ovarian cancer families taking advantage of a complete cancer registration database. A second objective was to determine the cancer phenotype of these families. Methods The original population database was composed of cancer patients from the Institute of Oncology Ljubljana in Slovenia which also includes current follow-up status on these patients. The inclusion criteria for the BRCA1/2 screening were: (i probands with at least two first degree relatives with breast and ovarian cancer; (ii probands with only two first degree relatives of breast cancer where one must be diagnosed less than 50 years of age; and (iii individual patients with breast and ovarian cancer, bilateral breast cancer, breast cancer diagnosed before the age of 40 and male breast cancer without any other cancer in the family. Results Probands from 150 different families met the inclusion criteria for mutation analysis of which 145 consented to testing. A BRCA1/2 mutation was found in 56 (39%. Two novel large deletions covering consecutive exons of BRCA1 were found. Five highly recurrent specific mutations were identified (1806C>T, 300T>G, 300T>A, 5382insC in the BRCA1 gene and IVS16-2A>G in the BRCA2 gene. The IVS16-2A>G in the BRCA2 gene appears to be a unique founder mutation in the Slovenian population. A practical implication is that only 4 PCR fragments can be used in a first screen and reveal the cancer predisposing mutation in 67% of the BRCA1/2 positive families. We also observed an exceptionally high frequency of 4 different pathogenic missense mutations, all affecting one of

  18. Familial pancreatic cancer: genetic advances

    OpenAIRE

    Rustgi, Anil K.

    2014-01-01

    This review by Rustgi elaborates on the known genetic syndromes that underlie familial pancreatic cancer. It aims to delineate the subtypes of syndromic hereditary pancreatic cancer in which germline genetic mutations have been identified and nonsyndromic familial pancreatic cancer in which genetic information is emerging.

  19. Breast and Colon Cancer Family Registries

    Science.gov (United States)

    The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.

  20. Familial aggregation of bladder cancer

    Directory of Open Access Journals (Sweden)

    Ilić Milena

    2011-01-01

    Full Text Available Background. Except for smoking and certain occupational exposures, the etiology of bladder cancer is largely unknown. Several case reports have described familial aggregation of transitional cell carcinoma of the bladder. Although the majority of patients with bladder cancer do not have family history of transitional cell carcinoma of the urinary tract, the study of familial transitional cell carcinoma may lead to the knowledge on the pathogenesis of this disease. The purpose of this study was to describe three cases of urinary bladder cancer in a single three-member family, i.e. in two generations (mother and son and a family member related by marriage (the patient’s wife. Case report. Three cases of urinary bladder cancer occurred in a three-member family within the interval of 5 years. The following common characteristics were detected in our patients: old age (over 60, working as farmers for more than 50 years, negative personal medical history on relevant health disorders, place of birth - village, place of residence - village, the same water supply, similar nutrition, positive family history on urinary bladder cancer or other malignant tumors, the first sign of illness was macroscopic hematuria in all the patients and the same pathohistological type of cancer - carcinoma papillare transitiocellulare. Conclusion. The stated common characteristics in our cases indicate, above all, the impact of exposure to external surrounding factors on the occurrence of urinary bladder cancer.

  1. Germline mutations in the breast cancer susceptibility gene PTEN are rare in high-risk non-BRCA1/2 French Canadian breast cancer families.

    Science.gov (United States)

    Guénard, Frédéric; Labrie, Yvan; Ouellette, Geneviève; Beauparlant, Charles Joly; Bessette, Paul; Chiquette, Jocelyne; Laframboise, Rachel; Lépine, Jean; Lespérance, Bernard; Pichette, Roxane; Plante, Marie; Durocher, Francine

    2007-01-01

    Cowden syndrome is a disease associated with an increase in breast cancer susceptibility. Alleles in PTEN and other breast cancer susceptibility genes would be responsible for approximately 25% of the familial component of breast cancer risk, BRCA1 and BRCA2 being the two major genes responsible for this inherited risk. In order to evaluate the proportion of high-risk French Canadian non-BRCA1/BRCA2 breast/ovarian cancer families potentially harboring a PTEN germline mutation, the whole coding and flanking intronic sequences were analyzed in a series of 98 breast cancer cases. Although no germline mutation has been identified in the coding region, our study led to the identification of four intronic variants. Further investigations were performed to analyze the effect of these variants, alone and/or in combination, on splicing and PTEN protein levels. Despite suggestive evidence emerging from in silico analyses, the presence of these intronic variants do not seem to alter RNA splicing or PTEN protein levels. In addition, as loss of PTEN or part of it has been reported, Western blot analysis has also been performed. No major deletion could be identified in our cohort. Therefore, assuming a Poisson distribution for the frequency of deleterious mutation in our cohort, if the frequency of such deleterious mutation was 2%, we would have had a 90% or greater chance of observing at least one such mutation. These results suggest that PTEN germline mutations are rare and are unlikely to account for a significant proportion of familial breast cancer cases in the French Canadian population.

  2. Increased tartrate-resistant acid phosphatase (TRAP expression in malignant breast, ovarian and melanoma tissue: an investigational study

    Directory of Open Access Journals (Sweden)

    Eck M

    2006-07-01

    Full Text Available Abstract Background Tartrate-resistant acid phosphatase (TRAP is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. Methods TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. Results A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. Conclusion Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies.

  3. Familial colorectal cancer type X

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Therkildsen, Christina; Da Silva, Sabrina;

    2015-01-01

    Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologi...... features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention.......Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic...

  4. A Pilot study of the Sharing Risk Information Tool (ShaRIT for Families with Hereditary Breast and Ovarian Cancer Syndrome

    Directory of Open Access Journals (Sweden)

    Kardashian Ani

    2012-04-01

    Full Text Available Abstract Background Individuals who carry deleterious BRCA mutations face significantly elevated risks of breast, ovarian, and other cancers. These individuals are also responsible for informing relatives of their increased risk for carrying the family BRCA mutation. Few interventions have been developed to facilitate this family communication process. Methods We developed the Sharing Risk Information Tool (ShaRIT, a personalized educational intervention, to support BRCA carriers as they discuss BRCA positive results and their implications with relatives. We conducted a pilot study of 19 BRCA carriers identified through the University of California San Francisco Cancer Risk Program. Our study had two aims: 1 to assess the feasibility and acceptability of ShaRIT, and 2 describe characteristics associated with increased family communication and BRCA testing. Participants in our study were divided into two groups: those who had not received ShaRIT as part of their genetic counseling protocol (control group, n = 10 and those who received ShaRIT (n = 9. Results All 9 women who received ShaRIT reported that it was a useful resource. Characteristics associated with increased sharing and testing included: female gender, degree of relationship, and frequency of communication. Increased pedigree knowledge showed a trend toward higher rates of sharing. Conclusions Both participants and genetic counselors considered ShaRIT a well-received, comprehensive tool for disseminating individual risk information and clinical care guidelines to Hereditary Breast and Ovarian Cancer Syndrome families. Because of this, ShaRIT has been incorporated as standard of care at our institution. In the future we hope to evaluate the effects of ShaRIT on family communication and family testing in larger populations of BRCA positive families.

  5. Genetic variants and haplotype analyses of the ZBRK1/ZNF350 gene in high-risk non BRCA1/2 French Canadian breast and ovarian cancer families.

    Science.gov (United States)

    Desjardins, Sylvie; Belleau, Pascal; Labrie, Yvan; Ouellette, Geneviève; Bessette, Paul; Chiquette, Jocelyne; Laframboise, Rachel; Lépine, Jean; Lespérance, Bernard; Pichette, Roxane; Plante, Marie; Durocher, Francine

    2008-01-01

    Our current understanding of breast cancer susceptibility involves mutations in the 2 major genes BRCA1 and BRCA2, found in about 25% of high-risk families, as well as few other low penetrance genes such as ATM and CHEK2. Approximately two-thirds of the multiple cases families remain to be explained by mutations in still unknown genes. In a candidate gene approach to identify new genes potentially involved in breast cancer susceptibility, we analyzed genomic variants in the ZBRK1 gene, a co-repressor implicated in BRCA1-mediated repression of GADD45. Direct sequencing of ZBRK1 entire coding region in affected breast cancer individuals from 97 high-risk French Canadian breast/ovarian cancer families and 94 healthy controls led to the identification of 18 genomic variants. Haplotype analyses, using PHASE, COCAPHASE and HaploStats programs, put in evidence 3 specific haplotypes which could potentially modulate breast cancer risk, and among which 2 that are associated with a potential protective effect (p = 0.01135 and p = 0.00268), while another haplotype is over-represented in the case group (p = 0.00143). Further analyses of these haplotypes indicated that a strong component of the observed difference between both groups emerge from the first 5 variants (out of 12 used for haplotype determination). The present study also permitted to determine a set of tagging SNPs that could be useful for subsequent analyses in large scale association studies. Additional studies in large cohorts and other populations will however be needed to further evaluate if common and/or rare ZBRK1 sequence variants and haplotypes could be associated with a modest/intermediate breast cancer risk.

  6. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence

    Directory of Open Access Journals (Sweden)

    Ihab Shafek Atta

    2016-01-01

    Full Text Available We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner’s, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A.

  7. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence.

    Science.gov (United States)

    Atta, Ihab Shafek; AlQahtani, Fahd Nasser

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812

  8. Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study.

    Science.gov (United States)

    Childs, Erica J; Chaffee, Kari G; Gallinger, Steven; Syngal, Sapna; Schwartz, Ann G; Cote, Michele L; Bondy, Melissa L; Hruban, Ralph H; Chanock, Stephen J; Hoover, Robert N; Fuchs, Charles S; Rider, David N; Amundadottir, Laufey T; Stolzenberg-Solomon, Rachael; Wolpin, Brian M; Risch, Harvey A; Goggins, Michael G; Petersen, Gloria M; Klein, Alison P

    2016-07-01

    Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13-1.63; P = 9.29 × 10(-4); 7p13, rs17688601: OR = 0.76; 95% CI, 0.63-0.93; P = 6.59 × 10(-3)). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185-91. ©2016 AACR. PMID:27197284

  9. Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer.

    Directory of Open Access Journals (Sweden)

    Wei-Ching Chen

    Full Text Available Dysregulated lipid metabolism contributes to cancer progression. Our previous study indicates that long-chain fatty acyl-Co A synthetase (ACSL 3 is essential for lipid upregulation induced by endoplasmic reticulum stress. In this report, we aimed to identify the role of ACSL family in cancer with systematic analysis and in vitro experiment. We explored the ACSL expression using Oncomine database to determine the gene alteration during carcinogenesis and identified the association between ACSL expression and the survival of cancer patient using PrognoScan database. ACSL1 may play a potential oncogenic role in colorectal and breast cancer and play a potential tumor suppressor role in lung cancer. Co-expression analysis revealed that ACSL1 was coexpressed with MYBPH, PTPRE, PFKFB3, SOCS3 in colon cancer and with LRRFIP1, TSC22D1 in lung cancer. In accordance with PrognoScan analysis, downregulation of ACSL1 in colon and breast cancer cell line inhibited proliferation, migration, and anchorage-independent growth. In contrast, increase of oncogenic property was observed in lung cancer cell line by attenuating ACSL1. High ACSL3 expression predicted a better prognosis in ovarian cancer; in contrast, high ACSL3 predicted a worse prognosis in melanoma. ACSL3 was coexpressed with SNUPN, TRIP13, and SEMA5A in melanoma. High expression of ACSL4 predicted a worse prognosis in colorectal cancer, but predicted better prognosis in breast, brain and lung cancer. ACSL4 was coexpressed with SERPIN2, HNRNPCL1, ITIH2, PROCR, LRRFIP1. High expression of ACSL5 predicted good prognosis in breast, ovarian, and lung cancers. ACSL5 was coexpressed with TMEM140, TAPBPL, BIRC3, PTPRE, and SERPINB1. Low ACSL6 predicted a worse prognosis in acute myeloid leukemia. ACSL6 was coexpressed with SOX6 and DARC. Altogether, different members of ACSLs are implicated in diverse types of cancer development. ACSL-coexpressed molecules may be used to further investigate the role of ACSL

  10. Family Ties: The Role of Family Context in Family Health History Communication About Cancer.

    Science.gov (United States)

    Rodríguez, Vivian M; Corona, Rosalie; Bodurtha, Joann N; Quillin, John M

    2016-01-01

    Family health history about cancer is an important prevention and health promotion tool. Yet few studies have identified family context factors that promote such discussions. We explored relations among family context (cohesion, flexibility, and openness), self-efficacy, and cancer communication (gathering family history, sharing cancer risk information, and frequency) in a diverse group of women enrolled in a randomized control trial. Baseline survey data for 472 women were analyzed. The women's average age was 34 years, 59% identified as Black, 31% had graduated high school, and 75% reported a family history of any cancer. Results showed that greater family cohesion and flexibility were related to higher communication frequency and sharing cancer information. Women who reported greater self-efficacy were more likely to have gathered family history, shared cancer risk information, and communicated more frequently with relatives. Openness was not associated with communication but was related to greater family cohesion and flexibility. Adjusting for demographic variables, self-efficacy, and family cohesion significantly predicted communication frequency. Women with higher self-efficacy were also more likely to have gathered family health history about cancer and shared cancer risk information. Future research may benefit from considering family organization and self-efficacy when developing psychosocial theories that in turn inform cancer prevention interventions.

  11. Family Ties: The Role of Family Context in Family Health History Communication About Cancer.

    Science.gov (United States)

    Rodríguez, Vivian M; Corona, Rosalie; Bodurtha, Joann N; Quillin, John M

    2016-01-01

    Family health history about cancer is an important prevention and health promotion tool. Yet few studies have identified family context factors that promote such discussions. We explored relations among family context (cohesion, flexibility, and openness), self-efficacy, and cancer communication (gathering family history, sharing cancer risk information, and frequency) in a diverse group of women enrolled in a randomized control trial. Baseline survey data for 472 women were analyzed. The women's average age was 34 years, 59% identified as Black, 31% had graduated high school, and 75% reported a family history of any cancer. Results showed that greater family cohesion and flexibility were related to higher communication frequency and sharing cancer information. Women who reported greater self-efficacy were more likely to have gathered family history, shared cancer risk information, and communicated more frequently with relatives. Openness was not associated with communication but was related to greater family cohesion and flexibility. Adjusting for demographic variables, self-efficacy, and family cohesion significantly predicted communication frequency. Women with higher self-efficacy were also more likely to have gathered family health history about cancer and shared cancer risk information. Future research may benefit from considering family organization and self-efficacy when developing psychosocial theories that in turn inform cancer prevention interventions. PMID:26735646

  12. Genetic Screening for Familial Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Oliveira Carla

    2004-05-01

    Full Text Available Abstract Approximately 10% of gastric cancer cases show familial clustering but only 1-3% of gastric carcinomas arise as a result of inherited gastric cancer predisposition syndromes. Direct proof that Hereditary Gastric Cancer a genetic disease with a germline gene defect has come from the demonstration of co-segregation of germline E-cadherin (CDH1 mutations with early onset diffuse gastric cancer in families with an autosomal dominant pattern of inheritance (HDGC. E-cadherin is a transmembrane calcium-dependent cell-adhesion molecule involved in cell-junction formation and the maintenance of epithelial integrity. In this review, we describe frequency and type of CDH1 mutations in sporadic and familial gastric cancer. Further we demonstrate the functional significance of some CDH1 germline missense mutations found in HDGC. We also discuss the CDH1 polymorphisms that have been associated to gastric cancer. We report other types of malignancies associated to HDGC, besides diffuse gastric cancer. Moreover, we review the data available on putative alternative candidate genes screened in familial gastric cancer. Finally, we briefly discuss the role of low-penetrance genes and Helicobacter pylori in gastric cancer. This knowledge is a fundamental step towards accurate genetic counselling, in which a highly specialised pre-symptomatic therapeutic intervention should be offered.

  13. Breast cancer susceptibility variants alter risk in familial ovarian cancer.

    Science.gov (United States)

    Latif, A; McBurney, H J; Roberts, S A; Lalloo, F; Howell, A; Evans, D G; Newman, W G

    2010-12-01

    Recent candidate gene and genome wide association studies have revealed novel loci associated with an increased risk of breast cancer. We evaluated the effect of these breast cancer associated variants on ovarian cancer risk in individuals with familial ovarian cancer both with and without BRCA1 or BRCA2 mutations. A total of 158 unrelated white British women (54 BRCA1/2 mutation positive and 104 BRCA1/2 mutation negative) with familial ovarian cancer were genotyped for FGFR2, TNRC9/TOX3 and CASP8 variants. The p.Asp302His CASP8 variant was associated with reduced ovarian cancer risk in the familial BRCA1/2 mutation negative ovarian cancer cases (P = 0.016). The synonymous TNRC9/TOX3 (Ser51) variant was present at a significantly lower frequency than in patients with familial BRCA1/2 positive breast cancer (P = 0.0002). Our results indicate that variants in CASP8 and TNRC9/TOX3 alter the risk of disease in individuals affected with familial ovarian cancer.

  14. Familial Colorectal Cancer: Understanding the Alphabet Soup.

    Science.gov (United States)

    Giglia, Matthew D; Chu, Daniel I

    2016-09-01

    While most colorectal cancers (CRCs) originate from nonhereditary spontaneous mutations, one-third of cases are familial or hereditary. Hereditary CRCs, which account for alphabet soup of genes to provide the highest quality of care for patients and families. PMID:27582643

  15. Prenatal and familial associations of testicular cancer.

    OpenAIRE

    Swerdlow, A J; Huttly, S. R.; Smith, P.G.

    1987-01-01

    In a case-control study of testis cancer 259 cases with testicular cancer, 238 controls treated at radiotherapy centres and 251 non-radiotherapy hospital in-patient controls were interviewed about some possible prenatal and familial risk factors for the tumour. For firstborn men, the risk of testis cancer increased significantly according to maternal age at the subject's birth, and this effect was most marked for seminoma. The association with maternal age was not apparent for cases other tha...

  16. Analysis of BRCA1 involvement in breast cancer in Indian women

    Indian Academy of Sciences (India)

    P H Pestonjamasp; I Mittra

    2000-03-01

    The involvement of the familial breast-ovarian cancer gene (BRCA1) in the molecular pathogenesis of breast cancer among Indian women is unknown. We have used a set of microsatellite polymorphisms to examine the frequency of allele loss at the BRCA1 region on chromosome 17q21, in a panel of 80 human breast tumours. Tumour and blood leukocyte/normal tissue DNA from a series of 80 patients with primary breast cancer was screened by PCR-amplified microsatellite length polymorphisms to detect deletions at three polymorphic BRCA1 loci. PCR-allelotype was valuable in examining allele losses from archival and small tumour samples. Loss of alleles at BRCA1 in the patient set, confirmed a noteworthy role of this gene in the molecular pathogenesis of breast cancer and was in accordance with its well-documented tumour suppressive function.

  17. Cancerous leptomeningitis and familial congenital hypopituitarism.

    Science.gov (United States)

    Vujovic, S; Vujosevic, S; Kavaric, S; Sopta, J; Ivovic, M; Saveanu, A; Brue, T; Korbonits, M; Popovic, V

    2016-05-01

    People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies. PMID:26886902

  18. RAD51B in Familial Breast Cancer

    Science.gov (United States)

    Pelttari, Liisa M.; Khan, Sofia; Vuorela, Mikko; Kiiski, Johanna I.; Vilske, Sara; Nevanlinna, Viivi; Ranta, Salla; Schleutker, Johanna; Winqvist, Robert; Kallioniemi, Anne; Dörk, Thilo; Bogdanova, Natalia V.; Figueroa, Jonine; Pharoah, Paul D. P.; Schmidt, Marjanka K.; Dunning, Alison M.; García-Closas, Montserrat; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Rosenberg, Efraim H.; Fasching, Peter A.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Nordestgaard, Børge G.; Benitez, Javier; González-Neira, Anna; Neuhausen, Susan L.; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Brüning, Thomas; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Van Dyck, Laurien; Janssen, Hilde; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Peterlongo, Paolo; Hallberg, Emily; Olson, Janet E.; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Schumacher, Fredrick; Simard, Jacques; Dumont, Martine; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Grip, Mervi; Andrulis, Irene L.; Glendon, Gord; Devilee, Peter; Seynaeve, Caroline; Hooning, Maartje J.; Collée, Margriet; Cox, Angela; Cross, Simon S.; Shah, Mitul; Luben, Robert N.; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Couch, Fergus J.; Yannoukakos, Drakoulis; Orr, Nick; Swerdlow, Anthony; Darabi, Hatef; Li, Jingmei; Czene, Kamila; Hall, Per; Easton, Douglas F.; Mattson, Johanna; Blomqvist, Carl; Aittomäki, Kristiina; Nevanlinna, Heli

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk. PMID:27149063

  19. RAD51B in Familial Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Liisa M Pelttari

    Full Text Available Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC that were genotyped on a custom chip (iCOGS. We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259 and population controls (n = 3586 from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR: 1.15, 95% confidence interval (CI: 1.11-1.19, P = 8.88 x 10-16 and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11, compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

  20. Estimates of heritable and environmental components of familial breast cancer using family history information

    OpenAIRE

    Couto, E; Hemminki, K

    2007-01-01

    Using the Swedish Family-Cancer Database, the increased risk of breast cancer in women with relatives with the disease did not vary with paternal/maternal lineage. Familial breast cancer heritable component was 73% and the environmental proportion 27%. Familial aggregation of breast cancer in women below age 51 years is mainly due to heritable causes.

  1. Cancer surveillance of patients from familial pancreatic cancer kindreds.

    Science.gov (United States)

    Brentnall, T A

    2000-05-01

    The family history can be used to determine which family members warrant surveillance and when to start it. Surveillance should be started at least 1 decade before the earliest age of pancreatic cancer in the family. EUS is the basic, least-invasive surveillance tool; however, findings are similar to those seen in chronic pancreatitis. All patients who have a positive EUS or who have symptoms warrant ERCP. Changes on ERCP of ductal stricturing and clubbed or saccular side branches are suggestive of patients who may need pancreatectomy in the setting of hereditary pancreatic cancer. The goal for surveillance of familial pancreatic cancer patients is to diagnose them before the development of cancer, when they have dysplasia or carcinoma in situ, and to perform a complete pancreatectomy. Timing is crucial for determining when a patient warrants surgery; if performed too early, the patient is put at risk for the morbidity and mortality of a total pancreatectomy, which is not inconsequential. If the patient survives the operation, he or she is often left a brittle diabetic. The alternative of diagnosing too late is more worrisome because the patient dies of pancreatic cancer. An essential ingredient to a good patient outcome is a team approach to these patients, using gastroenterologists, surgeons, and pathologists who have expertise and interest in pancreatic disease.

  2. The role of HER family signalling in breast cancer

    OpenAIRE

    Kuruppu, Anchala

    2016-01-01

    The HER family of receptors plays a major role in a variety of cancers including breast cancer. Several researchers have shown that HER family overexpression in breast cancer is a significant prognostic factor, especially for survival and relapse. Therefore, many therapeutics are being developed to test the impact of HER family blockade in breast cancer. Although numerous therapies have been developed, many have not been very successful in the clinic. This is often a consequence of cancer cel...

  3. Family Caregivers for Cancer Patients in Thailand

    Directory of Open Access Journals (Sweden)

    Warunee Meecharoen

    2013-08-01

    Full Text Available This integrative review was conducted to describe findings from Thai studies concerning family caregivers for cancer patients. Twenty-three studies that were published from 1994 to 2009 were considered. There were 15 quantitative studies and 8 qualitative studies. The stress and coping model developed by Lazarus and Folkman was the most popular theory that was used to guide the studies. The variables that were explored in the quantitative studies consisted of social support, stress, coping, caregiver burden, quality of life (QOL, and others. The qualitative findings revealed that there were several themes such as the following: the meaning of being family caregivers for cancer patients, the meaning of care, the experiences of caregivers, and the problems and needs of family caregivers in the Thai context. The evidence from the 23 studies reviewed showed that the state of knowledge of cancer caregivers in the Thai context is at an early stage compared with the state of knowledge in Western countries. More research needs to be done to explore the concepts related to negative and positive outcomes of caregiving.

  4. GENETIC OF THYROID CANCER FAMILIAL NON MEDULLARY THYROID CANCER

    Directory of Open Access Journals (Sweden)

    Silvia Cantara

    2012-08-01

    Full Text Available Differentiated non-medullary thyroid cancer (NMTC is mostly sporadic, but the recurrence of familial form of the disease has been reported. Short or dysfunctional telomeres have been associated with familial benign diseases and familial breast cancer. We aimed to study the telomere-telomerase complex in familial NMTC (FNMTC. The genetic analysis included the measurement in the peripheral blood of relative telomere length (RTL, telomerase reverse transcriptase (hTERT gene amplification, hTERT mRNA expression, telomerase protein activity and search of hTERT or TERC (telomerase RNA component gene mutations. We, also, studied telomeric fusions and associations as well as other chromosomal fragility features by conventional and molecular cytogenetic analyses, in phytohemagglutinin stimulated T-lymphocytes from familial patients, unaffected family members, sporadic PTC patients and healthy subjects. We found that, telomere lenght was significantly shorter in the blood of familial patients compared to sporadic PTCs, healthy subjects, nodular goiter and unaffected siblings. hTERT gene amplification was significantly higher in FNMTC patients compared to the other groups and, in particular, it was significantly greater in offspring with respect to parents. hTERT mRNA expression as well as telomerase activity were significantly higher in FNMTC patients compared to sporadic In addition, we demonstrated that familial patients have a significant increase in spontaneous telomeric associations and telomeric fusions compared to healthy subjects and sporadic cases. Q-FISH analysis demonstrated that familial cases display a significant decrease in the telomeric PNA-FISH signal intensity in metaphase chromsome. Our study demonstrates that patients with FNMTC display an imbalance of the telomeretelomerase complex in the peripheral blood.

  5. Linkage Analysis in Familial Non-Lynch Syndrome Colorectal Cancer Families from Sweden

    OpenAIRE

    Vinaykumar Kontham; Susanna von Holst; Annika Lindblom

    2013-01-01

    Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased ...

  6. Risk of gynecologic cancers in Danish hereditary non-polyposis colorectal cancer families

    DEFF Research Database (Denmark)

    Boilesen, Astrid Elisabeth Bruun; Bisgaard, Marie Luise; Bernstein, Inge

    2008-01-01

    OBJECTIVE: Women in hereditary non-polyposis colorectal cancer (HNPCC) families have an elevated risk of endometrial and ovarian cancer. The risk in Lynch syndrome families with known mutations in mismatch repair genes (MMR genes) seems to be higher than in familial colorectal cancer (CRC) famili...

  7. Clues to the pathogenesis of familial colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, L.A.; Peltomaeki, P.; Pylkkaenen, L.; Chappelle, A. de la (Univ. of Helsinki (Finland)); Leach, F.S.; Powell, S.M.; Jen, J.; Hamilton, S.R.; Petersen, G.M.; Kinzler, K.W.; Vogelstein, B. (Johns Hopkins Univ., Baltimore, MD (United States) Johns Hopkins Hospital, Baltimore, MD (United States)); Sistonen, P. (Univ. of Helsinki (Finland) Finnish Red Cross Blood Transfusion Service, Helsinki (Finland)); Mecklin, J.P. (Jyvaeskylae Central Hospital (Finland)); Jaervinen, H. (Helsinki Univ. Central Hospital (Finland))

    1993-05-07

    A predisposition to colorectal cancer is shown to be linked to markers on chromosome 2 in some families. Molecular features of familial cancers were compared with those of sporadic colon cancers. Neither the familial nor sporadic cancers showed loss of heterozygosity for chromosome 2 markers, and the incidence of mutations in KRAS, P53, and APC was similar in the two groups of tumors. Most of the familial cancers, however, had widespread alterations in short repeated DNA sequences, suggesting that numerous replication errors had occurred during tumor development. Thirteen percent of sporadic cancers had identical abnormalities and these cancers shared biologic properties with the familial cases. These data suggest a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes. 22 refs., 2 figs., 2 tabs.

  8. Methylenetetrahydrofolate Reductase Polymorphisms at Familial Bladder Cancer: Case Report

    OpenAIRE

    Gulay Ceylan

    2016-01-01

    Bladder cancer is the seventh most common cancer in men in the world, it is the second most seen cancer after lung cancer and the first in urogenital tumours in Turkey. Many molecular epidemiologic studies have been reported to investigate the associations between the MTHFR C677T and A1298C polymorphisms and bladder cancer risk. In this report, a family with transitional bladder cancer have also MTHFR A1298C heterozygosity which supports the association between MTHFR variants and bladder canc...

  9. Hereditary breast cancer. Psychosocial issues and family physicians' role.

    OpenAIRE

    Carroll, J. C.; Heisey, R. E.; Warner, E.; V Goel; McCready, D R

    1999-01-01

    OBJECTIVES: To outline the psychosocial issues in hereditary breast cancer (HBC) assessment and discuss the role of family physicians. QUALITY OF EVIDENCE: A literature search using MEDLINE, CINAHL, CancerLit, and HealthStar databases was conducted from January 1990 to April 1998, using the key words breast cancer or neoplasm and familial or hereditary, genetic testing or screening, primary care or family physician or counseling, genetic counseling, psychosocial or psychological. We found onl...

  10. Innovative Program Aims to Improve Support for Cancer Family Caregivers

    Science.gov (United States)

    An article about an educational program at the City of Hope Cancer Center intended to provide health professionals with the tools and information needed to help family caregivers care for themselves and their loved ones with cancer.

  11. Familial pancreatic carcinoma in Jews.

    Science.gov (United States)

    Lynch, Henry T; Deters, Carolyn A; Lynch, Jane F; Brand, Randall E

    2004-01-01

    Pancreatic cancer (PC) is the most fatal of all gastrointestinal cancers, wherein its mortality compares strikingly with its incidence. Unfortunately, 80-90% of PCs are diagnosed in the nonresectable stage. While the lifetime risk of PC in developed countries is approximately 1-3%, it is the fifth most common cause of cancer deaths among both males and females in Western countries. It occurs in excess in Jews. Approximately 5-10% of PC shows familial clustering. Examination of such familial clusters must take into consideration cancers of diverse anatomic sites, such as malignant melanoma in the familial atypical multiple melanoma (FAMMM) syndrome due to the CDKN2A (p16) germline mutation, and combinations of colorectal and endometrial carcinoma, ovarian carcinoma, and several other cancers in hereditary nonpolyposis colorectal cancer (HNPCC), which are due to mismatch repair germline mutations, the most common of which are MSH2 and MLH1 . Other hereditary disorders predisposing to PC include Peutz-Jeghers syndrome, due to the STK11 mutation, familial pancreatitis due to the cationic trypsinogen gene, site-specific familial pancreatic cancer which may be due to the 4q32-34 mutation, hereditary breast-ovarian cancer (HBOC) syndrome that is due to BRCA2 and possibly some families with HBOC that is due to BRCA1 , familial adenomatous polyposis due to the ATP gene, and ataxia telangiectasia due to the ATM germline mutation. This extant heterogeneity mandates that the physician be knowledgeable about these PC-prone syndromes which play such an important role when considering the differential diagnosis of hereditary PC. Unfortunately, there are no PC screening programs with acceptable sensitivity and specificity. However, the gold standard for screening at this time is endoscopic ultrasound. Clearly, there is a great need for the development of novel screening approaches with acceptable sensitivity and specificity. Further research is needed to elucidate those etiologic

  12. Retinoic acid and cancer treatment

    OpenAIRE

    Chen, Mei-Chih; Hsu, Shih-Lan; Lin, Ho; Yang, Tsung-Ying

    2014-01-01

    Retinoic acid which belongs to the retinoid class of chemical compounds is an important metabolite of vitamin A in diets. It is currently understood that retinoic acid plays important roles in cell development and differentiation as well as cancer treatment. Lung, prostate, breast, ovarian, bladder, oral, and skin cancers have been demonstrated to be suppressed by retinoic acid. Our results also show that low doses and high doses of retinoic acid may respectively cause cell cycle arrest and a...

  13. Family Adjustment to Childhood Cancer: A Systematic Review

    Science.gov (United States)

    Long, Kristin A.; Marsland, Anna L.

    2011-01-01

    This systematic review integrates qualitative and quantitative research findings regarding family changes in the context of childhood cancer. Twenty-eight quantitative, 42 qualitative, and one mixed-method studies were reviewed. Included studies focused on family functioning, marital quality, and/or parenting in the context of pediatric cancer,…

  14. Breast Cancer-Related Lymphedema: Implications for Family Leisure Participation

    Science.gov (United States)

    Radina, M. Elise

    2009-01-01

    An estimated 20% of breast cancer survivors face the chronic condition of breast cancer-related lymphedema. This study explored the ways in which women with this condition experienced changes in their participation in family leisure as one indicator of family functioning. Participants (N = 27) were interviewed regarding lifestyles before and after…

  15. Methylenetetrahydrofolate Reductase Polymorphisms at Familial Bladder Cancer: Case Report

    Directory of Open Access Journals (Sweden)

    Gulay Ceylan

    2016-02-01

    Full Text Available Bladder cancer is the seventh most common cancer in men in the world, it is the second most seen cancer after lung cancer and the first in urogenital tumours in Turkey. Many molecular epidemiologic studies have been reported to investigate the associations between the MTHFR C677T and A1298C polymorphisms and bladder cancer risk. In this report, a family with transitional bladder cancer have also MTHFR A1298C heterozygosity which supports the association between MTHFR variants and bladder cancer. This %uFB01nding should be further validated by prospective and larger studies with more diverse ethnic groups.

  16. DNA Double Strand Break Repair and its Association with Inherited Predispositions to Breast Cancer

    Directory of Open Access Journals (Sweden)

    Scott Rodney J

    2004-02-01

    Full Text Available Abstract Mutations in BRCA1 account for the majority of familial aggregations of early onset breast and ovarian cancer (~70% and about 1/5 of all early onset breast cancer families; in contrast, mutations in BRCA2 account for a smaller proportion of breast/ovarian cancer families and a similar proportion of early onset breast cancer families. BRCA2 has also been shown to be associated with a much more pleiotropic disease spectrum compared to BRCA1. Since the identification of both BRCA1 and BRCA2 investigations into the functions of these genes have revealed that both are associated with the maintenance of genomic integrity via their apparent roles in cellular response to DNA damage, especially their involvement in the process of double strand DNA break repair. This review will focus on the specific roles of both genes and how functional differences may account for the diverse clinical findings observed between families that harbour BRCA1 or BRCA2 mutations.

  17. Routine testing for PALB2 mutations in familial pancreatic cancer families and breast cancer families with pancreatic cancer is not indicated

    NARCIS (Netherlands)

    Harinck, Femme; Kluijt, Irma; van Mil, Saskia E.; Waisfisz, Quinten; van Os, Theo A. M.; Aalfs, Cora M.; Wagner, Anja; Olderode-Berends, Maran; Sijmons, Rolf H.; Kuipers, Ernst J.; Poley, Jan-Werner; Fockens, Paul; Bruno, Marco J.

    2012-01-01

    PALB2-mutation carriers not only have an increased risk for breast cancer (BC) but also for pancreatic cancer (PC). Thus far, PALB2 mutations have been mainly found in PC patients from families affected by both PC and BC. As it is well known that the prevalence of gene mutations varies between diffe

  18. Genetic susceptibility for specific cancers. Medical liability of the clinician.

    Science.gov (United States)

    Severin, M J

    1999-12-01

    The use of genetic profiling techniques to detect individuals with an increased susceptibility to heritable cancers has provoked recent legal interest in the duties of the attending physician and in the rights of patients and their families. In the current study specific prima facie and recently litigated cases are presented and explored to delineate the issues facing physicians and to illustrate the prerogatives of patients who are caught up in a heritable cancer enigma. Various courts have attempted to answer questions involving lawsuits in which incidents of breast/ovarian carcinoma and colon carcinoma have provoked claims of negligence against health care providers. Health care workers involved in the care of these patients have specific duties to these individuals. It would appear that physicians are being forced to assume the additional duty of delving into a patient's family history of cancer through multiple generations. This duty is followed by a responsibility to provide detailed counseling to those patients in whom such activity impacts the diagnosis and management of familial cancer.

  19. BREAST AND/OR OVARIAN CANCER AS PART OF FAMILY CANCER SYNDROME

    OpenAIRE

    L N Lyubchenko; N. I. Pospelova; A. A. Parokonnaya; A. A. Luzhnikova; E. M. Chevkina

    2014-01-01

    The problems in the early diagnosis, primary and secondary prevention of family cancer of the breast and/or ovaries are successfully solved within medical genetic counseling at a cancer clinic. Its genetic diagnosis is confirmed, individual risks for breast and/or ovarian cancer are calculated, risk-modifying factors are studied, and treatment, family planning, and childbirth are discussed during clinicogenetic studies.

  20. Urban family physicians and the care of cancer patients.

    OpenAIRE

    Dworkind, M.; Shvartzman, P; Adler, P. S.; Franco, E. D.

    1994-01-01

    Members in the Department of Family Medicine of a university teaching hospital were surveyed to find out their involvement in caring for cancer patients. Respondents indicated that many cancer patients were followed, but few cancer support services in the hospital and the community were used. The desire to take on new cancer patients was lacking, yet an interest in continuing medical education existed. Feedback from the department will help guide our Education Committee to develop continuing ...

  1. 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.

  2. Family Caregivers in Cancer (PDQ®)—Patient Version

    Science.gov (United States)

    Expert-reviewed information summary about the challenges faced by family caregivers of cancer patients. This summary focuses on typical caregiver roles and concerns, and helpful interventions for caregivers.

  3. Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

    DEFF Research Database (Denmark)

    Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina;

    2014-01-01

    BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several can...... colon cancer. CONCLUSIONS: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.......BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several...... cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. METHODS: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation...

  4. Management of familial cancer: sequencing, surveillance and society.

    Science.gov (United States)

    Samuel, Nardin; Villani, Anita; Fernandez, Conrad V; Malkin, David

    2014-12-01

    The clinical management of familial cancer begins with recognition of patterns of cancer occurrence suggestive of genetic susceptibility in a proband or pedigree, to enable subsequent investigation of the underlying DNA mutations. In this regard, next-generation sequencing of DNA continues to transform cancer diagnostics, by enabling screening for cancer-susceptibility genes in the context of known and emerging familial cancer syndromes. Increasingly, not only are candidate cancer genes sequenced, but also entire 'healthy' genomes are mapped in children with cancer and their family members. Although large-scale genomic analysis is considered intrinsic to the success of cancer research and discovery, a number of accompanying ethical and technical issues must be addressed before this approach can be adopted widely in personalized therapy. In this Perspectives article, we describe our views on how the emergence of new sequencing technologies and cancer surveillance strategies is altering the framework for the clinical management of hereditary cancer. Genetic counselling and disclosure issues are discussed, and strategies for approaching ethical dilemmas are proposed.

  5. Cancer Risk Assessment by Rural and Appalachian Family Medicine Physicians

    Science.gov (United States)

    Kelly, Kimberly M.; Love, Margaret M.; Pearce, Kevin A.; Porter, Kyle; Barron, Mary A.; Andrykowski, Michael

    2009-01-01

    Context: Challenges to the identification of hereditary cancer in primary care may be more pronounced in rural Appalachia, a medically underserved region. Purpose: To examine primary care physicians' identification of hereditary cancers. Methods: A cross-sectional survey was mailed to family physicians in the midwestern and southeastern United…

  6. Determining the familial risk distribution of colorectal cancer: a data mining approach.

    Science.gov (United States)

    Chau, Rowena; Jenkins, Mark A; Buchanan, Daniel D; Ait Ouakrim, Driss; Giles, Graham G; Casey, Graham; Gallinger, Steven; Haile, Robert W; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Win, Aung Ko

    2016-04-01

    This study was aimed to characterize the distribution of colorectal cancer risk using family history of cancers by data mining. Family histories for 10,066 colorectal cancer cases recruited to population cancer registries of the Colon Cancer Family Registry were analyzed using a data mining framework. A novel index was developed to quantify familial cancer aggregation. Artificial neural network was used to identify distinct categories of familial risk. Standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs) of colorectal cancer were calculated for each category. We identified five major, and 66 minor categories of familial risk for developing colorectal cancer. The distribution the major risk categories were: (1) 7% of families (SIR = 7.11; 95% CI 6.65-7.59) had a strong family history of colorectal cancer; (2) 13% of families (SIR = 2.94; 95% CI 2.78-3.10) had a moderate family history of colorectal cancer; (3) 11% of families (SIR = 1.23; 95% CI 1.12-1.36) had a strong family history of breast cancer and a weak family history of colorectal cancer; (4) 9 % of families (SIR = 1.06; 95 % CI 0.96-1.18) had strong family history of prostate cancer and weak family history of colorectal cancer; and (5) 60% of families (SIR = 0.61; 95% CI 0.57-0.65) had a weak family history of all cancers. There is a wide variation of colorectal cancer risk that can be categorized by family history of cancer, with a strong gradient of colorectal cancer risk between the highest and lowest risk categories. The risk of colorectal cancer for people with the highest risk category of family history (7% of the population) was 12-times that for people in the lowest risk category (60%) of the population. Data mining was proven an effective approach for gaining insight into the underlying cancer aggregation patterns and for categorizing familial risk of colorectal cancer.

  7. Role of chance in familial aggregaton of colorectal cancer

    DEFF Research Database (Denmark)

    Katballe, N.; Bentzen, S.M.; Christensen, M.;

    2001-01-01

    A prospective population-based study recorded family trees of 77 colorectal cancer patients younger than 50 years of age. Using mathematical modeling of population age-incidence data, we estimate that 1 (95% confidence limits 0 and 3) of these families is expected to meet the Amsterdam criteria I...

  8. History, Pathogenesis, and Management of Familial Gastric Cancer: Original Study of John XXIII's Family

    Directory of Open Access Journals (Sweden)

    Giovanni Corso

    2013-01-01

    Full Text Available Background. Hereditary diffuse gastric cancer is associated with the E-cadherin germline mutations, but genetic determinants have not been identified for familial intestinal gastric carcinoma. The guidelines for hereditary diffuse gastric cancer are clearly established; however, there are no defined recommendations for the management of familial intestinal gastric carcinoma. Methods. In this study we describe Pope John XXIII's pedigree that harboured gastric cancer as well as six other family members. Family history was analysed according to the International Gastric Cancer Linkage Consortium criteria, and gastric tumours were classified in accord with the last Japanese guidelines. Results. Seven out of 109 members in this pedigree harboured gastric cancer, affecting two consecutive generations. John XXIII's clinical tumour (cTN was classified as cT4bN3a (IV stage. In two other cases, gastric carcinomas were classified as intestinal histotype and staged as pT1bN0 and pT2N2, respectively. Conclusions. Pope John XXIII's family presents a strong aggregation for gastric cancer affecting almost seven members; it spreads through two consecutive generations. In absence of defined genetic causes and considering the increased risk of gastric cancer’s development in these families, as well as the high mortality rates and advanced stages, we propose an intensive surveillance protocol for asymptomatic members.

  9. Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden.

    Directory of Open Access Journals (Sweden)

    Vinaykumar Kontham

    Full Text Available Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121 and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737. Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683 and one on 17p13.2 (LOD/HLOD=2.0, rs884250. No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies.

  10. Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden.

    Science.gov (United States)

    Kontham, Vinaykumar; von Holst, Susanna; Lindblom, Annika

    2013-01-01

    Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121) and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737). Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683) and one on 17p13.2 (LOD/HLOD=2.0, rs884250). No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies. PMID:24349560

  11. Cancer as a complex phenotype: pattern of cancer distribution within and beyond the nuclear family.

    Directory of Open Access Journals (Sweden)

    Laufey T Amundadottir

    2004-12-01

    Full Text Available BACKGROUND: The contribution of low-penetrant susceptibility variants to cancer is not clear. With the aim of searching for genetic factors that contribute to cancer at one or more sites in the body, we have analyzed familial aggregation of cancer in extended families based on all cancer cases diagnosed in Iceland over almost half a century. METHODS AND FINDINGS: We have estimated risk ratios (RRs of cancer for first- and up to fifth-degree relatives both within and between all types of cancers diagnosed in Iceland from 1955 to 2002 by linking patient information from the Icelandic Cancer Registry to an extensive genealogical database, containing all living Icelanders and most of their ancestors since the settlement of Iceland. We evaluated the significance of the familial clustering for each relationship separately, all relationships combined (first- to fifth-degree relatives and for close (first- and second-degree and distant (third- to fifth-degree relatives. Most cancer sites demonstrate a significantly increased RR for the same cancer, beyond the nuclear family. Significantly increased familial clustering between different cancer sites is also documented in both close and distant relatives. Some of these associations have been suggested previously but others not. CONCLUSION: We conclude that genetic factors are involved in the etiology of many cancers and that these factors are in some cases shared by different cancer sites. However, a significantly increased RR conferred upon mates of patients with cancer at some sites indicates that shared environment or nonrandom mating for certain risk factors also play a role in the familial clustering of cancer. Our results indicate that cancer is a complex, often non-site-specific disease for which increased risk extends beyond the nuclear family.

  12. Efficacy of a touchscreen computer based family cancer history questionnaire and subsequent cancer risk assessment

    OpenAIRE

    Westman, J; Hampel, H.; Bradley, T.

    2000-01-01

    OBJECTIVE—A computer based touchscreen family cancer history questionnaire was developed and implemented to facilitate the provision of cancer risk assessments for the ambulatory and outpatient populations of a free standing cancer hospital.
METHODS—A questionnaire consisting of a series of branched point decision making screens was developed which enables the participant to enter demographic data, personal cancer history, and cancer histories for first and second degree relatives. A freestan...

  13. Cancer family history reporting: impact of method and psychosocial factors.

    Science.gov (United States)

    Kelly, Kimberly M; Shedlosky-Shoemaker, Randi; Porter, Kyle; Remy, Amber; DeSimone, Philip; Andrykowski, Michael A

    2007-06-01

    Family history is one the greatest risk factors for disease and one of the most important informational tools in medical genetics for the purpose of diagnosis, risk assessment, prevention and treatment. However, research is needed on the comparability of different methods of cancer family history assessment and the influence of psychosocial factors in family history reports. The purpose of this study was to determine if individuals had discrepancies between written and interview reports of cancer family history and the role of psychosocial factors in these discrepancies. Oncology patients (n=104) were administered a survey to assess psychosocial factors (i.e., information-seeking, worry, perceived risk, and health literacy) and were asked to provide family history in a written and an interview form. Randomization determined which form individuals received first. No differences in the amount of missing data or the amount of unspecified data were noted between the written and interview method. Psychosocial factors did not differentiate between those who had discrepancies in family history reports and those who did not have discrepancies in family history reports; although there was a trend for those with lower literacy and those who were blunters to be more discrepant on type of cancer diagnosis. In sum, this preliminary study indicates that written and interview methods of family history assessment for first degree relatives may be used interchangeably. The ability to use written methods will facilitate collection of basic family history information in the oncology clinic. PMID:17318453

  14. Cancer in the Family: Review of the Psychosocial Perspectives of Patients and Family Members

    Science.gov (United States)

    Mitschke, Diane B.

    2008-01-01

    As advances in cancer care have led to more treatment options and longer survival for cancer patients, a focus on quality of life for patients and their families has gained importance. This review provides a discussion of stress and coping theory, documents the relevance of this topic area for social work practice, and illuminates the results of a…

  15. Indication for CDKN2A-mutation analysis in familial pancreatic cancer families without melanomas

    NARCIS (Netherlands)

    Harinck, Femme; Kluijt, Irma; van der Stoep, Nienke; Oldenburg, Rogier A.; Wagner, Anja; Aalfs, Cora M.; Sijmons, Rolf H.; Poley, Jan-Werner; Kuipers, Ernst J.; Fockens, Paul; van Os, Theo A. M.; Bruno, Marco J.

    2012-01-01

    Background CDKN2A-mutation carriers run a high risk of developing melanomas and have an increased risk of developing pancreatic cancer (PC). Familial PC (FPC) patients with a personal history or family history of melanomas are therefore offered CDKN2A-mutation analysis. In contrast, CDKN2A testing i

  16. Race and colorectal cancer screening compliance among persons with a family history of cancer

    Institute of Scientific and Technical Information of China (English)

    Adeyinka; O; Laiyemo; Nicole; Thompson; Carla; D; Williams; Kolapo; A; Idowu; Kathy; Bull-Henry; Zaki; A; Sherif; Edward; L; Lee; Hassan; Brim; Hassan; Ashktorab; Elizabeth; A; Platz; Duane; T; Smoot

    2015-01-01

    AIM: To determine compliance to colorectal cancer(CRC) screening guidelines among persons with a family history of any type of cancer and investigate racial differences in screening compliance.METHODS: We used the 2007 Health Information National Trends Survey and identified 1094(27.4%)respondents(weighted population size = 21959672) without a family history of cancer and 3138(72.6%) respondents(weighted population size = 58201479) with a family history of cancer who were 50 years and older. We defined compliance with CRC screening as the use of fecal occult blood testing within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We compared compliance with CRC screening among those with and without a family member with a history of cancer. RESULTS: Overall, those with a family member with cancer were more likely to be compliant with CRC screening(64.9% vs 55.1%; OR = 1.45; 95%CI: 1.20-1.74). The absolute increase in screening rates associated with family history of cancer was 8.2% among whites. Hispanics had lowest screening rates among those without family history of cancer 41.9% but had highest absolute increase(14.7%) in CRC screening rate when they have a family member with cancer. Blacks had the lowest absolute increase in CRC screening(5.3%) when a family member has a known history of cancer. However, the noted increase in screening rates among blacks and Hispanics when they have a family member with cancer were not higher than whites without a family history of cancer:(54.5% vs 58.7%; OR = 1.16; 95%CI: 0.72-1.88) for blacks and(56.7% vs 58.7%; OR = 1.25; 95%CI: 0.72-2.18) for Hispanics.CONCLUSION: While adults with a family history of any cancer were more likely to be compliant with CRC screening guidelines irrespective of race/ethnicity, blacks and Hispanics with a family history of cancer were less likely to be compliant than whites without a family history. Increased burden from CRC among blacks may be related to poor uptake of

  17. Informing the cancer patient and family.

    Science.gov (United States)

    Kallergis, G

    2009-01-01

    One of the questions the therapist poses himself while informing a patient is: whom shall I inform about the diagnosis, treatment and prognosis? If we unconditionally accepted the view that information belongs to the patient from an ethical and legal standpoint, we would automatically exclude the partner and the family. Therefore, the therapist should raise another question: what is the benefit to the patient? To answer the question and the resulting dilemma, we have to leverage the long experience of family therapy and tailor it to the cases we are dealing with. It should be taken into consideration that patient and family are a dynamic system which was balanced before the onset of the disease, but is now disrupted, entering into crisis. Therefore, denial mechanism and personality characteristics we have previously elaborated on, and communication among members play a crucial role in determining the information strategy and the way family should be approached. The steps to approach the patient - family are: 1) Firstly, we evaluate the patient's degree of denial and personality characteristics. Then we receive information about the patient's family so that we can have a rough idea about intrafamily dynamics. 2) Then we gather information from the nurses about the family atmosphere: simple information about the patient's and relatives' relationship like who comes to the hospital, who shows interest in the patient, whether someone is being quarrelsome or not are crucial to assess the dynamics of their relationships. 3) We summon patient and family members in our office. 4) We decide on the steps to inform the patient, and we apply them. Involving family members with the patient seems to improve the results of information and forge concession and therapeutic alliance, which are necessary parameters in the therapeutic follow-up. Usually, doctors and nurses approach patient and family using their experience. Therefore, we need a training that will equip health

  18. The contribution of founder mutations in BRCA1 to breast cancer in Belarus.

    Science.gov (United States)

    Uglanitsa, N; Oszurek, O; Uglanitsa, K; Savonievich, E; Lubiński, J; Cybulski, C; Debniak, T; Narod, S A; Gronwald, J

    2010-10-01

    Mutations in the BRCA1 gene increase susceptibility to both breast and ovarian cancer. In some countries, including several in Eastern Europe, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases. To estimate the hereditary proportion of breast cancer in Belarus, we sought the presence of any of three founder mutations in BRCA1 (4153delA, 5382insC and C61G) in 500 unselected cases of breast cancer. These mutations have previously been identified in breast/ovarian cancer families from Belarus and from other Slavic countries, including Poland and Russia. One of the three founder mutations in BRCA1 was present in 38 of 500 unselected cases of breast cancer (7.6%). A mutation was found in 12.6% of women diagnosed before age 50 and 5.6% of women diagnosed after age 50. A mutation was identified in 2 of 251 newborn controls (0.8%). The hereditary proportion of breast cancers in Belarus is among the highest of any countries studied to date.

  19. Case Report: Familial Gastric Cancer and Chordoma in the Same Family

    Directory of Open Access Journals (Sweden)

    Weber Walter

    2005-05-01

    Full Text Available Abstract Gastric cancers are the second most common malignancy in the world and represent a major burden to all societies even though the incidence of disease is decreasing in the industrialized world. The aetiology of the disease is complex and is believed to be primarily due to environmental factors but a small proportion of cases are recognised as being associated with genetic factors. Two inherited forms of stomach cancer have been identified, one which is associated with familial clusterings of stomach cancer and the other being a subgroup of families that belong to hereditary non polyposis colorectal cancer (or Lynch syndrome. In this report we present a small nuclear family which is unusual in that there is a clustering of malignancy which includes stomach cancer, colorectal cancer and chordoma. Genetic analysis failed to reveal any causative mutation in genes associated with HNPCC or in E-cadherin. Together, the clinical picture in this family may indicate that other genetic factors are behind this family's clustering of malignancy.

  20. BREAST AND/OR OVARIAN CANCER AS PART OF FAMILY CANCER SYNDROME

    Directory of Open Access Journals (Sweden)

    L. N. Lyubchenko

    2009-01-01

    Full Text Available The problems in the early diagnosis, primary and secondary prevention of family cancer of the breast and/or ovaries are successfully solved within medical genetic counseling at a cancer clinic. Its genetic diagnosis is confirmed, individual risks for breast and/or ovarian cancer are calculated, risk-modifying factors are studied, and treatment, family planning, and childbirth are discussed during clinicogenetic studies.

  1. Familial skin cancer syndromes: Increased melanoma risk.

    Science.gov (United States)

    Ransohoff, Katherine J; Jaju, Prajakta D; Jaju, Prajaka D; Tang, Jean Y; Carbone, Michele; Leachman, Sancy; Sarin, Kavita Y

    2016-03-01

    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings.

  2. African American Women’s Limited Knowledge and Experiences with Genetic Counseling for Hereditary Breast Cancer

    OpenAIRE

    Sheppard, Vanessa B.; Graves, Kristi D.; Christopher, Juleen; Hurtado-de-Mendoza, Alejandra; Talley, Costellia; Williams, Karen Patricia

    2013-01-01

    Genetic counseling and testing for hereditary breast cancer have the potential benefit of early detection and early interventions in African American women. However, African American women have low use of these services compared to White women. We conducted two focus groups with African American women diagnosed with breast cancer (affected group, n=13) and women with at least one first-degree relative with breast/ovarian cancer (unaffected group, n= 8). A content analysis approach was employe...

  3. Survival models for familial aggregation of cancer.

    OpenAIRE

    Mack, W.; Langholz, B; Thomas, D. C.

    1990-01-01

    It has recently been shown that the relative risks of the order of 2 to 4 that are frequently found for cancer among relatives of affected cases are unlikely to be explainable by shared environmental risk factors. Classical methods of epidemiological analysis are not well suited to such analysis because they assume that the outcomes of each individual are independent. Classical methods of genetic analysis, on the other hand, are limited in their handling of environmental factors and variable ...

  4. Hereditary nonpolyposis colorectal cancer and familial colorectal cancer in Central part of Iran, Isfahan

    Directory of Open Access Journals (Sweden)

    Amin Nemati

    2012-01-01

    Full Text Available Background: There is a lack of data on familial aggregation of colorectal cancer (CRC in Iran. We aimed to deter-mine the frequency of hereditary nonpolyposis colorectal cancer (HNPCC and familial colorectal cancer (FCC and to determine the frequency of extracolonic cancers in these families in Isfahan. Methods: We reviewed documents of all patients with a pathologically confirmed diagnosis of CRC admitted to Isfa-han referral hospitals between 1995 and 2006. We also studied our CRC registry at Poursina Hakim Research Institute from 2003 to 2008. We found HNPCC and FCC families based on the Amsterdam II criteria and interviewed them for family history of CRC and extracolonic tumors. The family history was taken at least up to the second-degree relatives. Results: During 1996 to 2008, a total of 2580 CRC cases have been diagnosed. We found 14 HNPCC and 53 FCC families. Mean age of CRC at diagnosis was 48.0 ΁ 14.6 and 49.0 ΁ 13.9 years in the HNPCC and FCC families, re-spectively (p > 0.05. The total numbers of observed extracolonic tumors were 70 (21.6%; mean age = 53.6 ΁ 11.0 years and 157 (13.8%; mean age = 54.8 ΁ 18.0 years in HNPCC and FCC families, respectively (p > 0.05. CRC was respectively found in 52 and 76 members of the HNPCC and FCC families, revealing the frequency of HNPCC and FCC as 2.0% (52/2580 and 2.9% (76/2580, respectively. Conclusions: We found a relative high frequency of HNPCC (2.0% and FCC (2.9% among CRC cases in our socie-ty and high incidence of extracolonic tumors in their families. Further studies focusing on molecular basis in this field and designing a specific screening and national cancer registry program for HNPCC and FCC families should be con-ducted.

  5. Resilience in Families of Husbands with Prostate Cancer

    Science.gov (United States)

    Greeff, Abraham P.; Thiel, Colleen

    2012-01-01

    This study identifies qualities associated with the successful adaptation of families with a husband diagnosed with prostate cancer. Both qualitative and quantitative measures were used in this cross-sectional survey research design. Twenty-one husbands and their spouses independently completed six questionnaires and a biographical questionnaire,…

  6. Clinical and biological characteristics of colorectal cancer with familial predisposition

    Institute of Scientific and Technical Information of China (English)

    WU Bao-ping; ZHANG Ya-li; ZHOU Dian-yuan; GAO Chun-fang; LAI Zhuo-sheng

    2001-01-01

    To evaluate the microsatellite instability (MSI), expression of mismatch repair (MMR) gene (hMLH1, hMSH2) and proliferation kinetics in colorectal cancer (CRC) with familial predisposition. Method:Forty-six cases of CRC were studied using silver staining polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, streptavidin-peroxidase (SP) immunohistochemical method and flow cytometry. Results: In CRC patients with familial predisposition, the MSI-positive rate was higher than in sporadic CRC (P<0.05). Familial predisposition and positive MSI were strongly related to early age of cancer onset, the proclivity for proximal colonic cancer, poor differentiated and extracolorectaln malignancies (P<0.01, P<0.05). The incidence of negative expression ofhMLH1 in tumor tissue and hMLH1, hMSH2 in normal colorectal tissues was significantly higher (P<0.05). The negative expression of hMLH1 together with hMSH2 was related with positive MSI (P<0.05).In MSI-positive CRC cells, the proliferation cell nucleus antigen (PCNA) expression, proliferation index and S-phase cells decreased obviously (P<0.01, P<0.05). Conclusion: In CRC with familial predisposition, MSI might be an important contributor. The rate ofhMLH1 and hMSH2 mutation increased in tumor and normal tissue, and the proliferation activity of their cancer cell was lower.

  7. Cell biology of cancer: BRCA1 and sister chromatid pairing reactions?

    Science.gov (United States)

    Skibbens, Robert V

    2008-02-15

    A significant portion of familial breast/ovarian cancer patients harbors a mutation in Breast Cancer Associated gene 1 (BRCA1). Cells deficient for BRCA1 exhibit chromosome aberrations such as whole chromosome duplications, translocations, inter-sister gaps and gene mis-regulation. Here, new evidence is reviewed that defects in sister chromatid cohesion may contribute directly to cancer cell phenotypes-especially those of BRCA1 mutant cells. Linking cohesion to BRCA1-dependent tumorigenesis are reports that BRCA1-associated components (DNA helicase, RFC, PCNA and genome surveillance factors) are required for efficient sister chromatid cohesion. Other cohesion factors (WAPL, EFO2/ESCO2 and hSecurin) are tightly correlated with various cell-type specific carcinogenesis, in support of a generalized model for cohesion in cancer. Recent findings further reveal that a reciprocal relationship exists in that DNA damage induces new Ctf7/Eco1-dependent sister chromatid pairing reactions that, in turn, are required for efficient DNA repair. Future research into sister chromatid pairing mechanisms are likely to provide critical new insights into the underlying causes of cancer.

  8. Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families : high cancer incidence at older age

    NARCIS (Netherlands)

    van der Kolk, Dorina M.; de Bock, Geertruida H.; Leegte, Beike K.; Schaapveld, Michael; Mourits, Marian J. E.; de Vries, J; van der Hout, Annemieke H.; Oosterwijk, Jan C.

    2010-01-01

    Accurate estimations of lifetime risks of breast and ovarian cancer are crucial for counselling women from BRCA1/2 families. We therefore determined breast and ovarian cancer penetrance in BRCA1/2 mutation families in the northern Netherlands and compared them with the incidence of cancers in the ge

  9. Impact of family history of breast cancer on tumour characteristics, treatment, risk of second cancer and survival among men with breast cancer

    OpenAIRE

    Bouchardy Magnin, Christine; Rapiti Aylward, Elisabetta; Fioretta, Gérald; Schubert, Hyma; Chappuis, Pierre; Vlastos, Georges; Benhamou, Simone

    2013-01-01

    Male breast cancer patients have a higher risk of developing a second primary cancer, but whether this risk differs according to the family history of breast or ovarian cancers remains to be elucidated. We aimed to determine the effect of a positive family history among men diagnosed with breast cancer on tumour characteristics, treatment, second cancer occurrence and overall survival.

  10. Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer

    OpenAIRE

    Silverman, D.T. (Debra T.); Schiffman, M; Everhart, J; Goldstein, A.; Lillemoe, K D; Swanson, G.M.; Schwartz, A. G.; Brown, L.M.; Greenberg, R S; Schoenberg, J. B.; Pottern, L M; Hoover, R. N.; Fraumeni, J. F.

    1999-01-01

    In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible c...

  11. The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women

    Energy Technology Data Exchange (ETDEWEB)

    Abeliovich, D.; Lerer, I.; Weinberg, N. [Hebrew Univ. Medical School, Jerusalem (Israel)

    1997-03-01

    The mutations 185delAG, 188del11, and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene were analyzed in 199 Ashkenazi and 44 non-Ashkenazi Jewish unrelated patients with breast and/or ovarian cancer. Of the Jewish Ashkenazi women with ovarian cancer, 62% (13/21) had one of the target mutations, as did 30% (13/43) of women with breast cancer alone diagnosed before the age 40 years and 10% (15/141) of those with breast cancer diagnosed after the age 40 years. Age at ovarian cancer diagnosis was not associated with carrier status. Of 99 Ashkenazi patients with no family history of breast and/or ovarian cancer, 10% carried one of the mutations; in two of them the mutation was proved to be paternally transmitted. One non-Ashkenazi Jewish ovarian cancer patient from Iraq carried the 185delAG mutation. Individual mutation frequencies among breast cancer Ashkenazi patients were 6.7% for 185delAG, 2.2% for 5382insC, and 4.5% for 6174delT, among ovarian cancer patients; 185delAG and 6174delT were about equally common (33% and 29%, respectively), but no ovarian cancer patient carried the 5382insC. More mutations responsible for inherited breast and ovarian cancer probably remain to be found in this population, since 79% of high-incidence breast cancer families and 35% of high-incidence breast/ovarian cancer families had none of the three known founder mutations. 25 refs., 3 figs., 6 tabs.

  12. [Psychological and familial aspects of the familial breast and ovarian cancer genetic counseling process].

    Science.gov (United States)

    Flugelman, Anath; Rennert, Gad; Eidelman, Shmuel

    2014-01-01

    Breast cancer is the most prevalent malignancy among women, whilst ovarian cancer is less common but carries a graver prognosis. Carriers of the BRCA mutations have a few-fold higher risk for those diseases. Genetic counseling for the families at risk has been available for almost two decades, since the definition of the mutation. The existence of the deleterious mutation has implications beyond the individual level and touches the lives and future of many other family members. Being part of a BRCA family has medical as well as psychosocial implications. Various barriers and facilitators must be dealt with during the process of sharing the information with kins. Most families cope well with those issues, while some require the guidance of professionals. Special subpopulations, i.e. non-carrier women in BRCA families, young carriers and men who are under minimal personal threat but might transfer the mutation to their off springs, have special needs which should be addressed. The desired outcome of the counseling process is achievement of normal adaptation which balances life in the shadow of uncertainty and threat with the ability to lead a normal life. The process of counseling is multidisciplinary, and along with the advances in scientific and medical aspects, the ethical, legal and social implications (ELSI) have also been developed. The professional personnel escorting those families need to develop and maintain specific skills.

  13. Validity of self-reported family history of cancer: A systematic literature review on selected cancers.

    Science.gov (United States)

    Fiederling, Jonas; Shams, Ahmad Zia; Haug, Ulrike

    2016-10-01

    Evidence regarding validity of self-reported family history of cancer (FHC) has been reviewed only for breast, colorectal, prostate, ovarian, endometrial and uterine cancer. We aimed to systematically review studies assessing validity of self-reported family history for the remaining cancer sites. We searched the Medline database for relevant studies published by January 2016. We extracted information on the study design and the positive predictive value (PPV) of self-reported FHC, defined as the proportion of reported cancer diagnoses among relatives that was confirmed by a reference standard (as a measure of over-reporting). We also extracted information on sensitivity of self-reported FHC (as a measure of underreporting). Overall, 21 studies were included that provided information on the PPV of self-reported FHC for relevant cancers and four studies also provided information on sensitivity. The PPV was highest (mostly >70%) for pancreatic, lung, thyroid and urinary system cancers and for leukemia and lymphoma, while it was lowest for stomach and liver cancer. Sensitivity was highest (>70%) for pancreatic cancer, lung cancer, brain cancer, melanoma, leukemia and lymphoma. For several cancers, sample sizes were low and the number of studies limited, particularly regarding sensitivity of self-reported FHC. In conclusion, for some cancers (e.g., pancreatic cancer, lung cancer, leukemia, lymphoma) self-reported FHC can be considered sufficiently valid to be useful, for example, in preventive counseling. For several cancers, it is not sufficiently studied or the pattern is inconsistent. This needs to be taken into account when using self-reported information about FHC in clinical practice or epidemiological research. PMID:27222437

  14. P53 family and cellular stress responses in cancer

    Directory of Open Access Journals (Sweden)

    Johanna ePflaum

    2014-10-01

    Full Text Available p53 is an important tumor suppressor gene, which is stimulated by cellular stress like ionizing radiation, hypoxia, carcinogens and oxidative stress. Upon activation p53 leads to cell cycle arrest and promotes DNA repair or induces apoptosis via several pathways. p63 and p73 are structural homologs of p53 that can act similarly to the protein but also hold functions distinct from p53. Today more than forty different isoforms of the p53 family members are known. They result from transcription via different promoters and alternative splicing. Some isoforms have carcinogenic properties and mediate resistance to chemotherapy. Therefore, expression patterns of the p53 family genes can offer prognostic information in several malignant tumors. Furthermore, the p53 family constitutes a potential target for cancer therapy. Small molecules (e.g. Nutlins, RITA, PRIMA-1, and MIRA-1 among others have been objects of intense research interest in recent years. They restore pro-apoptotic wild-type p53 function and were shown to break chemotherapeutic resistance. Due to p53 family interactions small molecules also influence p63 and p73 activity. Thus, the members of the p53 family are key players in the cellular stress response in cancer and are expected to grow in importance as therapeutic targets.

  15. p53 Family: Role of Protein Isoforms in Human Cancer

    Directory of Open Access Journals (Sweden)

    Jinxiong Wei

    2012-01-01

    Full Text Available TP53, TP63, and TP73 genes comprise the p53 family. Each gene produces protein isoforms through multiple mechanisms including extensive alternative mRNA splicing. Accumulating evidence shows that these isoforms play a critical role in the regulation of many biological processes in normal cells. Their abnormal expression contributes to tumorigenesis and has a profound effect on tumor response to curative therapy. This paper is an overview of isoform diversity in the p53 family and its role in cancer.

  16. Family history of cancer and risk of Pancreatic Cancer: A Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    OpenAIRE

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-De-Mesquita, H Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e. ovarian, breast, and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of five types of cancer (pancreas, prostate, ovarian, br...

  17. Cancer patients' use of family practice and secondary care

    DEFF Research Database (Denmark)

    Sokolowski, Ineta; Kjeldgaard, Anette Hvenegaard; Olesen, Frede;

    recently diagnosed with cancer and among previous cancer patients. Materials and methods: In a nationwide database in Denmark (population 5.5 million) all contacts to the health care system are registered. We describe the pattern of contact with all parts of the health care system for a) the total...... who have recently undergone treatment and patients in the survivorship phase of cancer use different parts of the health care system, and how much they use FP. Information about this will enable us to discuss the need for shared care, integrated care and information exchange and create a platform for......Aims: We know that in Denmark some 90% of citizens have contact with family practice (FP) during a year and around 40% has contact with secondary care.  This demands efforts to create integrated and shared care. The aim of this study is to document the pattern of contacts with FP among patients...

  18. Family aggregation study for breast cancer in Cienfuegos province

    International Nuclear Information System (INIS)

    Breast cancer is one of the most frequent causes of death in developed countries and it is the second cause of female mortality for malignant tumor in Cuba. We conducted an observational, analytic, transversal study of cases and controls for the purpose of evaluating the clinical, epidemiologic and genealogical behavior of breast cancer in Cienfuegos province, in a period of 6 years. The universe of the study was made up of 304 women distributed in 152 cases and 152 controls; they were surveyed after they gave their informed consent. Collected data were processed by means of methods of inferential statistics. It was observed that most of the cases were diagnosed in patients aged 50 to 59 years, with 24.34%, the most frequent type was infiltrating duct carcinoma, with 43.42%. We found statistical association with the personal history of benign breast pathology and the family history of cancer of any type. Presence of familial aggregation was observed for breast cancer in the first-degree relatives and the non-genetic risk factors; they did not show significant association with the occurrence of the disease in the studied population

  19. The Relationship between Socio-demographic Characteristics, Family Environment, and Caregiver Coping in Families of Children with Cancer

    OpenAIRE

    Gage-Bouchard, Elizabeth A.; Devine, Katie A.; Heckler, Charles E.

    2013-01-01

    The factors that influence caregiver coping mechanism preferences after a child’s diagnosis with cancer are not fully understood. This study examines the relationship between caregivers’ socio-demographic characteristics and the coping strategies they use to adapt to childhood cancer. Sixty caregivers of pediatric cancer patients completed a socio-demographic questionnaire, the Family Environment Scale, and the COPE inventory. There were no significant differences in family environment by inc...

  20. Prospective surveillance of women with a family history of breast cancer: auditing the risk threshold

    OpenAIRE

    Anderson, E.; Berg, J; Black, R; Bradshaw, N.; Campbell, J.; Carnaghan, H; Cetnarkyj, R; Drummond, S; Davidson, R; Dunlop, J.; Fordyce, A.; Gibbons, B; Goudie, D; Gregory, H; Holloway, S

    2008-01-01

    To evaluate current guidelines criteria for inclusion of women in special ‘breast cancer family history' surveillance programmes, records were reviewed of women referred to Scottish breast cancer family clinics between January 1994 and December 2003 but discharged as at ‘less than ‘moderate' familial risk'. The Scottish Cancer Registry was then interrogated to determine subsequent age-specific incidence of breast cancer in this cohort and corresponding Scottish population figures. Among 2074 ...

  1. Screening for urinary tract cancer with urine cytology in Lynch syndrome and familial colorectal cancer

    DEFF Research Database (Denmark)

    Myrhøj, T; Andersen, M-B; Bernstein, I

    2008-01-01

    AIM: The aim of this study was to evaluate if Urine Cytology (UC) is an appropriate screening procedure for detecting urinary tract neoplasia at an early stage in persons at risk in Hereditary Non-Polyposis Colorectal Cancer families. METHOD: In the National Danish HNPCC-register persons at risk...... were identified in three categories of HNPCC-families (1) families harbouring a disease causing mutation in a Mismatch repair gene (MMR), (2) families fulfilling the Amsterdam I or II criteria and (3) families suspected of HNPCC. In total 3,411 persons were identified and traced in Patobank......) UC lead to a false positive screening diagnosis. During the study period fourteen persons (1.4%) developed a UTC and five of these were interval tumours. The sensitivity of UC in diagnosing asymptomatic UTC in HNPCC patients was 29%. Twelve of the tumours were found in persons from families...

  2. Universality of ageing: family caregivers for elderly cancer patients

    Directory of Open Access Journals (Sweden)

    Lea eBaider

    2014-07-01

    Full Text Available The world population is ageing, with the proportion of older people (65+ years expected to reach 21% in 2050 and to exceed the number of younger people (aged 15 or less for the first time in history. Because cancer is particularly a chronic disease of older people, a large increase in the number of elderly patients with cancer is anticipated. The estimated number of new cancer cases worldwide among people over 65 is expected to grow from about 6 million in 2008 to more than 11 million during the coming decade. By 2030, individuals over 65 are expected to account for 70% of all cancer patients in the Western world.Along with the increase in oncology patients, the number of older people caring for their ill spouses or other relatives is also growing, with the ensuing toll on these caregivers causing major concern, especially in western countries.In different societies the characteristics of family caregiver stressors, cultural norms concerning care giving, and the availability of support have a huge impact on those providing care. Any study of older caregivers of older cancer patients requires an integrative evaluation of ageing that takes into account cultural, social, psychological, and behavioral variables.This review proposes a critical discussion of the multidimensionality of the caregiving and of the impact that age, culture and gender have on it.

  3. A Review on Family History of Breast Cancer: Screening and Counseling Proposals for Women with Familial (Non-Hereditary) Breast Cancer.

    Science.gov (United States)

    Unic, Ivana; Stalmeier, Peep F. M.; Peer, Petronella G. M.; van Daal, Willem A. J.

    1997-01-01

    Studies of variables predicting familial breast cancer (N=59) were analyzed to develop screening recommendations for women with nonhereditary familial breast cancer present. The pooled relative risk (RR) and cumulative probability were used to estimate risk. Data and conclusions are presented. Recommendations for screening and counseling are…

  4. Linking Genetic Counseling Content to Short-Term Outcomes in Individuals at Elevated Breast Cancer Risk

    Science.gov (United States)

    Ellington, Lee; Schoenberg, Nancy; Agarwal, Parul; Jackson, Thomas; Dickinson, Stephanie; Abraham, Jame; Paskett, Electra D.; Leventhal, Howard; Andrykowski, Michael

    2014-01-01

    Few studies have linked actual genetic counseling content to short-term outcomes. Using the Self-regulation Model, the impact of cognitive and affective content in genetic counseling on short-term outcomes was studied in individuals at elevated risk of familial breast-ovarian cancer. Surveys assessed dependent variables: distress, perceived risk, and 6 knowledge measures (Meaning of Positive Test; Meaning of Negative Test; Personal Behavior; Practitioner Knowledge; Mechanisms of Cancer Inheritance; Frequency of Inherited Cancer) measured at pre- and post-counseling. Proportion of participant cognitive and affective and counselor cognitive and affective content during sessions (using LIWC software) were predictors in regressions. Knowledge increased for 5 measures and decreased for Personal Behavior, Distress and Perceived Risk. Controlling for age and education, results were significant/marginally significant for three measures. More counselor content was associated with decreases in knowledge of Personal Behavior. More participant and less counselor affective content was associated with gains in Practitioner Knowledge. More counselor cognitive, and interaction of counselor cognitive and affective content, were associated with higher perceived risk. Genetic counselors dominate the content of counseling sessions. Therefore, their content is tied more closely to short term outcomes than participant content. A lack of patient communication in sessions may pose problems for understanding of complex concepts. PMID:24671341

  5. Does family history of prostate cancer affect outcomes following radiotherapy?

    International Nuclear Information System (INIS)

    Objective: To examine family history (FH) as a prognostic factor following radiotherapy (RT). Materials and methods: Between 1989 and 2007, 1711 men with clinically localized prostate cancer and complete family history who had received RT (median RT dose = 74 Gy) without androgen deprivation therapy were analyzed. FH was defined as any prostate cancer in a first degree relative. For the biochemical failure (BF) outcome, this sample size has 85% power to detect a hazard ratio of 1.56 for positive versus negative FH. Results: With a median follow-up of 71 months, there was no significant difference in the distribution of Gleason score (GS) or prostate specific antigen (PSA) based on FH. A positive FH was not an independent predictor of BF, distant metastasis (DM), prostate cancer specific mortality (PCSM), or overall mortality (OM) in Cox proportional multivariable analysis. On further analysis in a Cox proportional multivariable analysis, men with two or more first degree relatives with prostate cancer had a significantly higher likelihood of BF and DM than those with no FH, although there was no difference in PCSM or OM. Men with a positive FH (23%) were more likely to be younger, have a lower PSA, and non-palpable disease. There was no interaction between a positive FH and neither race nor treatment era (pre-PSA vs. PSA era). Conclusions: A positive FH is not a prognostic factor following RT and should not alter standard treatment recommendations. Patients with two or more first degree relatives with prostate cancer had a higher likelihood of BF and DM, but there was no effect on survival. There was no interaction between a positive FH and African American race or treatment era. A positive FH was however, associated with more favorable PSA values and T-stage that may be the result of earlier screening

  6. RNA profiling reveals familial aggregation of molecular subtypes in non-BRCA1/2 breast cancer families

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Tan, Qihua;

    2014-01-01

    BACKGROUND: In more than 70% of families with a strong history of breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to be involved. It has been proposed that tumors with similar molecular phenotypes also share similar...... underlying pathophysiological mechanisms. In the current study, the aim was to investigate if global RNA profiling can be used to identify functional subgroups within breast tumors from families tested negative for BRCA1/2 germline mutations and how these subgroupings relate to different breast cancer...... cancer subtypes, exist among non-BRCA1/2 breast cancers. The distribution of subtypes was markedly different from the distribution found among BRCA1/2 mutation carriers. From 11 breast cancer families, breast tumor biopsies from more than one affected family member were included in the study. Notably...

  7. Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer

    Science.gov (United States)

    Roberts, Nicholas J.; Norris, Alexis L.; Petersen, Gloria M.; Bondy, Melissa L.; Brand, Randall; Gallinger, Steven; Kurtz, Robert C.; Olson, Sara H.; Rustgi, Anil K.; Schwartz, Ann G.; Stoffel, Elena; Syngal, Sapna; Zogopoulos, George; Ali, Syed Z.; Axilbund, Jennifer; Chaffee, Kari G.; Chen, Yun-Ching; Cote, Michele L.; Childs, Erica J.; Douville, Christopher; Goes, Fernando S.; Herman, Joseph M.; Iacobuzio-Donahue, Christine; Kramer, Melissa; Makohon-Moore, Alvin; McCombie, Richard W.; McMahon, K. Wyatt; Niknafs, Noushin; Parla, Jennifer; Pirooznia, Mehdi; Potash, James B.; Rhim, Andrew D.; Smith, Alyssa L.; Wang, Yuxuan; Wolfgang, Christopher L.; Wood, Laura D.; Zandi, Peter P.; Goggins, Michael; Karchin, Rachel; Eshleman, James R.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Hruban, Ralph H.; Klein, Alison P.

    2015-01-01

    Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genome of 638 familial pancreatic cancer patients. We also sequenced the exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A and ATM, and identify novel candidate genes harboring rare, deleterious germline variants for further characterization. We also show how somatic point mutations that occur during hematopoiesis can affect the interpretation of genome-wide studies of hereditary traits. Our observations have important implications for the etiology of pancreatic cancer and for the identification of susceptibility genes in other common cancer types. PMID:26658419

  8. Casting a Wider Net: Engaging Community Health Worker Clients and Their Families in Cancer Prevention.

    Science.gov (United States)

    Roman, Lee Anne; Zambrana, Ruth Enid; Ford, Sabrina; Meghea, Cristian; Williams, Karen Patricia

    2016-01-01

    Engaging family members in an intervention to prevent breast and cervical cancer can be a way to reach underserved women; however, little is known about whether family member recruitment reaches at-risk women. This study reports the kin relationship and risk characteristics of family members who chose to participate in the Kin Keeper(SM) cancer prevention intervention, delivered by community health workers (CHWs) via existing community programs. African American, Latina, and Arab family members reported risk factors for inadequate screening, including comorbid health conditions and inadequate breast or cervical cancer literacy. CHW programs can be leveraged to reach underserved families with cancer preventive interventions. PMID:27634780

  9. Mammographic density and breast cancer: a comparison of related and unrelated controls in the Breast Cancer Family Registry

    OpenAIRE

    Linton, Linda; Martin, Lisa J.; Li, Qing; Huszti, Ella; Minkin, Salomon; John, Esther M.; Rommens, Johanna; Paterson, Andrew D.; Boyd, Norman F

    2013-01-01

    Introduction Percent mammographic density (PMD) is a strong and highly heritable risk factor for breast cancer. Studies of the role of PMD in familial breast cancer may require controls, such as the sisters of cases, selected from the same 'risk set' as the cases. The use of sister controls would allow control for factors that have been shown to influence risk of breast cancer such as race/ethnicity, socioeconomic status and a family history of breast cancer, but may introduce 'overmatching' ...

  10. A decision exercise to engage cancer patients and families in Deliberation about Medicare Coverage for advanced Cancer Care

    OpenAIRE

    Danis, Marion; Abernethy, Amy P; Zafar, S Yousuf; Samsa, Gregory P.; Wolf, Steven P; Howie, Lynn; Taylor, Donald H.

    2014-01-01

    Background Concerns about unsustainable costs in the US Medicare program loom as the number of retirees increase and experiences serious and costly illnesses like cancer. Engagement of stakeholders, particularly cancer patients and their families, in prioritizing insured services offers a valuable strategy for informing Medicare coverage policy. We designed and evaluated a decision exercise that allowed cancer patients and family members to choose Medicare benefits for advanced cancer patient...

  11. Family history in breast cancer is not a prognostic factor?

    Science.gov (United States)

    Jobsen, J J; Meerwaldt, J H; van der Palen, J

    2000-04-01

    The aim of this study is to determine if breast conservative treatment is justified for patients with a positive family history of breast cancer and to investigate whether they have a worse prognosis. We performed a prospective cohort study of breast cancer patients, treated with breast conservative treatment with radiotherapy at the Radiotherapy Department of the Medisch Spectrum Twente. Between 1984 and 1996, 1204 patients with T1 and T2 or =2 FDRs. The local recurrence rate was 4.1%, with similar rates for all groups. In young patients, or =2 FDRs. Patients with a positive FH had significantly more contralateral tumours. The 5-year corrected survival was 91.3%. Among patients with a positive FH, a 5-year corrected survival of 91% was observed and the survival 100% among patients with one and > or =2 FDR. Family history is not a contraindication for breast conservative treatment and is not associated with a worse prognosis. Family history is not a prognostic factor for local recurrence rate in patients older than 40 years.

  12. The Importance of Older Family Members in Providing Social Resources and Promoting Cancer Screening in Families with a Hereditary Cancer Syndrome

    Science.gov (United States)

    Ashida, Sato; Hadley, Donald W.; Goergen, Andrea F.; Skapinsky, Kaley F.; Devlin, Hillary C.; Koehly, Laura M.

    2011-01-01

    Purpose: This study evaluates the role of older family members as providers of social resources within familial network systems affected by an inherited cancer susceptibility syndrome. Design and Methods: Respondents who previously participated in a study that involved genetic counseling and testing for Lynch syndrome and their family network…

  13. Spiritual Coping: A Gateway to Enhancing Family Communication During Cancer Treatment.

    Science.gov (United States)

    Prouty, Anne M; Fischer, Judith; Purdom, Ann; Cobos, Everardo; Helmeke, Karen B

    2016-02-01

    The researchers examined the spiritual coping, family communication, and family functioning of 95 participants in 34 families by an online survey. Multilevel linear regression was used to test whether individuals' and families' higher endorsement of more use of spiritual coping strategies to deal with a member's cancer would be associated with higher scores on family communication and family functioning, and whether better communication would also be associated with higher family functioning scores. Results revealed that spiritual coping was positively associated with family communication, and family communication was positively associated with healthier family functioning. The researchers provide suggestions for further research. PMID:26311053

  14. Importance of psychological support for families of children with cancer

    Directory of Open Access Journals (Sweden)

    Kaćanski Nataša

    2012-01-01

    Full Text Available Introduction. A family of a child with cancer needs continuous help and support from medical and other professionals, relatives, friends and community at the moment of making diagnosis and during the treatment. The goal of this study was to find out the most frequent sources of individual or community based psychological support, reported by parents of children suffering from malignant diseases. We focused on the help received at the moment of making diagnosis and within the first and second year of treatment. Material and Methods. We analyzed data obtained by a questionnaire specially designed for parents of children suffering from different malignancies. The poll was conducted from April 2007 till October 2009 at the Hematology/ Oncology Department of Children’s Hospital of Novi Sad and it included 72 parents of both sexes, whose children were treated at our Department in the period from 2007 to 2009. The children were of different age. Results. The parents selected the following forms of support as the most important: support given by the emotional partner and other family members (together with sick and healthy child, communication with and accessibility of hospital stuff (physicians at the first place, but also psychologists, nurses, other parents, support groups…. They also expressed their need for contacting friends, relatives and other close people. The selected forms of support are extremely important for the patients (regardless of age and for their family. All forms of organized and professionally conducted psycho-social support of patients and their family result in higher quality of psychological survival during the treatment and further rehabilitation of patients after rejoining their primary social environment. Conclusion. Family is the primary and the most important social surrounding within which disease both happens and is resolved. Adequate support can help family to overcome such crises, thus leading to the positive

  15. The Effects of a Genetic Counseling Educational Program on Hereditary Breast Cancer for Korean Healthcare Providers

    OpenAIRE

    Lee, Jihyoun; Cho, Hyung Jung; Yoo, Han-Wook; Park, Sue K.; Yang, Jae Jeong; Kim, Sung-Won; Kang, Eunyoung; Ahn, Sei-Hyun; Lee, Soo-Jung; Suh, Young Jin; Kim, Sung Yong; Kim, Eun-Kyu; Moon, Nan Mo; Lee, Min Hyuk; ,

    2013-01-01

    Purpose Systematic educational programs and genetic counseling certification courses for hereditary breast/ovarian cancer (HBOC) have not yet been introduced in Korea. We provided and evaluated the effects of genetic counseling education on Korean healthcare providers' knowledge, awareness, and counseling skills for patients at high risk of HBOC. Methods A 3-day educational program was conducted for healthcare providers who were interested in genetic counseling for patients at high risk of HB...

  16. Family history of cancer and risk of pancreatic cancer : a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    NARCIS (Netherlands)

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H. M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could

  17. Influence of family size and birth order on risk of cancer: a population-based study

    OpenAIRE

    Sundquist Jan; Thomsen Hauke; Weires Marianne; Bevier Melanie; Hemminki Kari

    2011-01-01

    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 socioeco...

  18. Accuracy of Self-Reported Breast Cancer Information among Women from the Ontario Site of the Breast Cancer Family Registry

    OpenAIRE

    Andriana Barisic; Gord Glendon; Nayana Weerasooriya; Andrulis, Irene L.; Knight, Julia A.

    2012-01-01

    Obtaining complete medical record information can be challenging and expensive in breast cancer studies. The current literature is limited with respect to the accuracy of self-report and factors that may influence this. We assessed the agreement between self-reported and medical record breast cancer information among women from the Ontario site of the Breast Cancer Family Registry. Women aged 20–69 years diagnosed with incident breast cancer 1996–1998 were identified from the Ontario Cancer R...

  19. Genetic variation at 8q24, family history of cancer, and upper gastrointestinal cancers in a Chinese population.

    Science.gov (United States)

    Tarleton, Heather P; Chang, Shen-Chih; Park, Sungshim Lani; Cai, Lin; Ding, Baoguo; He, Na; Hussain, Shehnaz K; Jiang, Qingwu; Mu, Li-Na; Rao, Jianyu; Wang, Hua; You, Nai-Chieh Y; Yu, Shun-Zhang; Zhao, Jin-Kou; Zhang, Zuo-Feng

    2014-03-01

    Genetic variation at 8q24 is associated with prostate, bladder, breast, colorectal, thyroid, lung, ovarian, UADT, liver and stomach cancers. However, a role for variation at 8q24 in familial clustering of upper gastrointestinal cancers has not been studied. In order to explore potential inherited susceptibility, we analyzed epidemiologic data from a population-based case-control study of upper gastrointestinal cancers from Taixing, China. The study population includes 204 liver, 206 stomach, and 218 esophageal cancer cases and 415 controls. Associations between 8q24 rs1447295, rs16901979, rs6983267 and these cancers were stratified by family history of cancer. Odds ratios and 95% confidence intervals were adjusted for potential confounders: age, sex, education, tobacco smoking, alcohol consumption, and BMI at interview. We also adjusted for hepatitis B and aflatoxin (liver cancer) and Helicobacter pylori (stomach cancer). In a dominant model, among those with a family history of cancer, rs1447295 was positively associated with liver cancer (OR(adj) 2.80; 95% CI 1.15-6.80). Heterogeneity was observed (P(heterogeneity) = 0.029) with rs6983267 and liver cancer, with positive association in the dominant model among those with a family history of cancer and positive association in the recessive model among those without a family history of cancer. When considered in a genetic risk score model, each additional 8q24 risk genotype increased the odds of liver cancer by two-fold among those with a family history of cancer (OR(adj) 2.00; 95% CI 1.15-3.47). These findings suggest that inherited susceptibility to liver cancer may exist in the Taixing population and that variation at 8q24 might be a genetic component of that inherited susceptibility. PMID:24030569

  20. Multiple primary colorectal cancer: Individual or familial predisposition?

    Institute of Scientific and Technical Information of China (English)

    José; A; Pajares; José; Perea

    2015-01-01

    Colorectal carcinoma(CRC) is one of the most frequent cancers. Along the surface of the large bowel, several foci of CRC may appear simultaneously or over the time. The development of at least two different tumours has been defined as multiple primary CRC(MPCRC):When more than one tumour is diagnosed at the same time, it is known as synchronous CRC(SCRC), while when a second neoplasm is diagnosed some time after the resection and/or diagnosis of the first lesion, it is called metachronous CRC(MCRC). Multiple issues can promote the development of MPCRC, ranging from different personal factors, such as environmental exposure, to familial predisposition due to hereditary factors. However, most studies do not distinguish this dichotomy. High- and low-pentrance genetic variants are involved in MPCRC. An increased risk for MPCRC has been described in Lynch syndrome, familial adenomatous polyposis, and serrated polyposis. Non-syndromic familial CRCs should also be considered as risk factors for MPCRC. Environmental factors can promote damage to colon mucosae that enable the concurrence of MPCRC. Epigenetics are thought to play a major role in the carcinogenesis of sporadic MPCRC. The methylation state of the DNA depends on multiple environmental factors(e.g., smoking and eating foods cooked at high temperatures), and this can contribute to increasing the MPCRC rate. Certain clinical features may also suggest individual predisposition for MPCRC. Different etiopathogenic factors are suspected to be involved in SCRC and MCRC, and different familial vs individual factors may be implicated. MCRC seems to follow a familial pattern, whereas individual factors are more important in SCRC. Further studies must be carried out to know the molecular basis of risks for MPCRC in order to modify, if necessary, its clinical management, especially from a preventive point of view.

  1. Linkage analysis with markers on 17q in 29 Swedish breast cancer families.

    OpenAIRE

    Lindblom, A; Rotstein, S; Nordenskjöld, M; Larsson, C.

    1993-01-01

    Recently, a putative breast cancer gene was localized to the long arm of chromosome 17. A collaboration study was undertaken to confirm linkage, to further map the gene, and to determine to what extent breast cancer families are linked to this locus. The Swedish material consisted of 29 breast cancer families in which 68 affected members were studied. Linkage analysis of breast cancer susceptibility was performed with a number of markers on 17q. In this material a weakly positive LOD score in...

  2. Role for CD40L in the Therapy of Human Cancer

    Institute of Scientific and Technical Information of China (English)

    Feng Wei; Xiubao Ren; Xishan Hao

    2005-01-01

    CD40L-CD40 interaction is central to the control of thymusdependent humoral .immunity and cell mediated immune responses.CD40, a member of the tumor necrosis factor receptor (TNF- R) family,has been found on the surface of B lymphocytes, monocytes, hematopoietic progenitors, dendritic cells (DCs), endothelial cells, epithelial cells and so on. Its natural ligand (CD40 ligand, CD40L), CD154, a member of the tumor necrosis factor (TNF) family, is mainly expressed on activated CD4+ T lymphocytes. A direct growth-inhibitory effect can be found when ligated CD40 is on human breast, ovarian, cervical, bladder, non-small cell lung, and squamous epithelial carcinoma cells. This effect is related to the induction of cell cycle blockage and/or apoptosis. CD40L induces phenotypic and functional maturation of DCs, and can increase tumor immunogenicity through up-regulation of costimulatory molecular expression and cytokine production by epithelial cancer cells. As a result,CD40L can enhance tumor rejection immune responses. Furthermore, by means of a "bystander effect", even CD40-negative tumor subsets can be eliminated by activated tumor-reactive cytotoxic T lymphocytes(CTL),This review summarizes recent findings on CD40L recombinant protein and gene therapy-based tumor treatment approaches.

  3. Mutations in BRCA1 and BRCA2 in breast cancer families: Are there more breast cancer-susceptibility genes?

    Energy Technology Data Exchange (ETDEWEB)

    Serova, O.M.; Mazoyer, S.; Putet, N. [CNRS, Lyon (France)] [and others

    1997-03-01

    To estimate the proportion of breast cancer families due to BRCA1 or BRCA2, we performed mutation screening of the entire coding regions of both genes supplemented with linkage analysis of 31 families, 8 containing male breast cancers and 23 site-specific female breast cancer. A combination of protein-truncation test and SSCP or heteroduplex analyses was used for mutation screening complemented, where possible, by the analysis of expression level of BRCA1 and BRCA2 alleles. Six of the eight families with male breast cancer revealed frameshift mutations, two in BRCA1 and four in BRCA2. Although most families with female site-specific breast cancers were thought to be due to mutations in either BRCA1 or BRCA2, we identified only eight mutations in our series of 23 site-specific female breast cancer families (34%), four in BRCA1 and four in BRCA2. According to the posterior probabilities calculated for mutation-negative families, based on linkage data and mutation screening results, we would expect 8-10 site-specific female breast cancer families of our series to be due to neither BRCA1 nor BRCA2. Thus, our results suggest the existence of at least one more major breast cancer-susceptibility gene. 24 refs., 1 fig., 3 tabs.

  4. CHEK2 1100delC is prevalent in Swedish early onset familial breast cancer

    Directory of Open Access Journals (Sweden)

    Lindblom Annika

    2007-08-01

    Full Text Available Abstract Background A truncating variant, 1100delC, in check point-kinase CHEK2, has been identified as a risk factor for familial and sporadic breast cancer. The prevalence in healthy non-breast cancer cases is low and varies between populations. Methods We analyzed the prevalence of CHEK2 1100delC in 763 breast cancer patients with a defined family history and 760 controls from the Stockholm region. The breast cancer patients originated from; a population-based cohort (n = 452 and from a familial cancer clinic (n = 311, the detailed family history was known in both groups. Results The variant was found in 2.9% of the familial cases from the population-based cohort and in 1.9% from the familial cancer clinic. In total 2.2% of the patients with a family history of breast cancer carried the variant compared to 0.7% of the controls (p = 0.03. There was no increased prevalence in sporadic patients (0.3%. The variant was most frequent in young familial patients (5.1% of cases ≤45 years, p = 0.003. The mean age at diagnosis of variant carriers was 12 years lower than in non-carriers (p = 0.001. Conclusion In conclusion, CHEK2 1100delC exists in the Swedish population. The prevalence is increased in familial breast cancer and the variant seems to influence age at onset.

  5. Role of ErbB receptors in cancer cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Aline eAppert-Collin

    2015-11-01

    Full Text Available Growth factors mediate their diverse biologic responses (regulation of cellular proliferation, differentiation, migration and survival by binding to and activating cell-surface receptors with intrinsic protein kinase activity named Receptor Tyrosine Kinases (RTKs. About 60 RTKs have been identified and can be classified into more than 16 different receptor families. Their activity is normally tightly controlled and regulated. Overexpression of RTK proteins or functional alterations caused by mutations in the corresponding genes or abnormal stimulation by autocrine growth factor loops contribute to constitutive RTK signaling, resulting in alterations in the physiological activities of cells. The ErbB receptor family of RTKs comprises four distinct receptors: the EGFR (also known as ErbB1/HER1, ErbB2 (neu, HER2, ErbB3 (HER3 and ErbB4 (HER4. ErbB family members are often overexpressed, amplified, or mutated in many forms of cancer, making them important therapeutic targets. EGFR has been found to be amplified in gliomas and non-small-cell lung carcinoma while ErbB2 amplifications are seen in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other tumor types. Several data have shown that ErbB receptor family and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion by modulating extracellular matrix components. Recent findings indicate that extracellular matrix components such as matrikines bind specifically to EGF receptor and promote cell invasion. In this review, we will present an in-depth overview of the structure, mechanisms, cell signaling, and functions of ErbB family receptors in cell adhesion and migration. Furthermore, we will describe in a last part the new strategies developed in anti-cancer therapy to inhibit ErbB family receptor activation.

  6. Clinical and genetic features of International Collaborative Group-hereditary nonpolyposis colorectal cancer families and suspected hereditary nonpolyposis colorectal cancer families

    Institute of Scientific and Technical Information of China (English)

    袁瑛; 叶俊; 郑树

    2004-01-01

    Background Hereditary nonpolyposis colorectal cancer (HNPPC) is one of the most common genetic syndrome related with mutation of human mismatch repair genes. This study was to evaluate the clinical significance of suspected hereditary nonpolyposis colorectal cancer (sHNPCC) criteria I and the clinical and genetic features of International Collaborative Group-HNPCC (ICG-HNPCC) and sHNPCC families.Methods Twenty-nine ICG-HNPCC families fulfilling the Amsterdam criteria and 34 sHNPCC families fulfilling the sHNPCC criteria I were collected. PCR-SSCP and DNA sequencing analysis were employed to screen the germline mutations of the hMLH1 and hMSH2 genes in these families.Results The ICG group had more colorectal cancer (CRC) patients per family than did the suspected group (P0.05), mutation type, and mutation distribution. Comparison of the families with and without mutation showed no significant difference in CRC patients per family, Lynch classification, and tumor spectrum.Conclusions ICG-HNPCC and sHNPCC families that have similar clinical manifestations and genetic basis indicate a similar nature for cancer development. The application of sHNPCC criteria I will facilitate clinical diagnosis and treatment of small families.

  7. Brief Report: Family cancer history affecting risk of colorectal cancer in a prospective cohort of Chinese women

    OpenAIRE

    Murphy, Gwen; Shu, Xiao Ou; Gao, Yu-Tang; Ji, Bu-Tian; Cook, Michael Blaise; YANG, Gong; Li, Hong-Lan; Rothman, Nathaniel; Zheng, Wei; Chow, Wong-Ho

    2009-01-01

    An elevated risk of colorectal cancer has been associated with sporadic colorectal cancer in first degree relatives, mostly in Western populations. Limited data exists from traditionally low-risk areas, such as Asia, where the prevalence of risk factors may differ. We examined the association of family history of cancer and subsequent colorectal cancer risk in a cohort of traditionally low-risk Chinese women.

  8. Genetic variations in SMAD7 are associated with colorectal cancer risk in the colon cancer family registry.

    Directory of Open Access Journals (Sweden)

    Xuejuan Jiang

    Full Text Available Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry.23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression.Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12-1.49, and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70-0.92 were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps.SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs.

  9. "It's not Just Camp!": Understanding the Meaning of Children's Cancer Camps for Children and Families.

    Science.gov (United States)

    Laing, Catherine M; Moules, Nancy J

    2016-01-01

    The purpose of this philosophical hermeneutic inquiry was to understand the meaning of children's cancer camps for the child with cancer and the family. Six childhood cancer families and 5 cancer camp counselors were interviewed, in order to bring understanding to this topic. Findings from this research revealed that camp means different things for different families, and that much is at play in the cancer camp experience: the healing and developmental power of play, finding acceptance and fit, grief as something to live with versus "get over," storytelling as a means of reshaping and understanding traumatic experiences, and the solidarity of the community as one that creates intense, healing bonds. Children's cancer camps, we conclude, should be considered a necessity, versus a luxury, and could even be thought of as a psychosocial intervention for some children and families. Barriers such as structure of funding and access to resources are present and likely due to the separateness of camps from hospital programs. PMID:25643975

  10. "Shifting family boundaries" after the diagnosis of childhood cancer in stepfamilies.

    Science.gov (United States)

    Patterson Kelly, Katherine; Ganong, Lawrence H

    2011-02-01

    The childhood cancer experiences of stepfamilies have not been described despite the fact that nearly one third of U.S. children will live in a stepfamily household. To describe the impact of diagnosis on parental relationships in stepfamilies, we undertook a secondary analysis of data from a study of parental decision making in structurally diverse families. As described by 13 parents of six stepfamilies, the crisis of a childhood cancer diagnosis immediately changed family dynamics. Parental relationships changed, which shifted family boundaries, creating instability in families who were trying to cope with a very stressful life experience. Through increased understanding of parental relationship changes that occur after the diagnosis of childhood cancer in stepfamilies, clinicians can anticipate these changes and provide supportive interventions to reduce overall family conflict and distress. These distinctive stepfamily responses underscore the need to include structurally diverse families in future trials targeting parental coping in childhood cancer.

  11. The relationship between family history of cancer, coping style and psychological distress

    OpenAIRE

    Liu, Yu; Cao, Chunmei

    2014-01-01

    Objective: To investigate the relationship between family history of cancer, coping style and psychological distress. Methods: Total 80 patients with family history of cancer and 72 normal controls were analyzed using self-reporting inventory (SCL-90), coping style scale and impact of event scale-revised (IES-R). Results: 1. Between the two groups of patients, there were significant differences in anxiety, depression, cancer-specific distress and coping style. 2. Psychological distress (anxie...

  12. Familial aggregation of lung cancer in a high incidence area in China

    OpenAIRE

    Jin, Y. T.; Xu, Y C; Yang, R D; Huang, C. F.; Xu, C W; He, X Z

    2005-01-01

    To investigate whether lung cancer clusters in families in a high incidence county of China, an analysis was conducted using data on domestic fuel history and tobacco use for family members of 740 deceased lung cancer probands and 740 controls (probands' spouses). Lung cancer prevalence was compared among first-degree relatives of probands and of controls, taking into account various factors using logistic regression and generalised estimating equations. First-degree relatives of probands, co...

  13. Association of family risk and lifestyle/comorbidities in ovarian cancer patients

    NARCIS (Netherlands)

    Teixeira, Natalia; Azevedo Koike Folgueira, Maria Aparecida; Maistro, Simone; Encinas, Giselly; de Bock, Geertruida Hendrika; Estevez Diz, Maria Del Pilar

    2015-01-01

    Objectives: to analyze factors that might indicate familial predisposition for ovarian cancer in patients diagnosed with this disease. Methods: in a prospective single center cohort study at the Institute of Cancer of the State of Sao Paulo (ICESP), 51 women diagnosed with ovarian cancer were includ

  14. The importance of family history in young patients with endometrial cancer

    NARCIS (Netherlands)

    Berends, MJW; Kleibeuker, JH; de Vries, EGE; Mourits, MJE; Hollema, H; Pras, E; van der Zee, AGJ

    1999-01-01

    Endometrial cancer occurs primarily in postmenopausal women older than 60 years of age. Especially in young patients with endometrial cancer, a positive family history with respect to cancer and/or development of synchronous or metachronous tumors can be indicative of hereditary factors. One generic

  15. 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.

  16. Influence of family size and birth order on risk of cancer: a population-based study

    International Nuclear Information System (INIS)

    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

  17. Grief Responses of Turkish Families after the Death of Their Children from Cancer

    Science.gov (United States)

    Cimete, Guler; Kuguoglu, Sema

    2006-01-01

    The aim of this qualitative study was to determine what the emotional reactions, experiences, and coping and support systems of families would be after the death of their children from cancer. The sample comprised 19 family members from five families. At the time of the interviews, it had been 8-14 months since the death of their children. The…

  18. Radiation exposure and familial aggregation of cancers as risk factors for colorectal cancer after radioiodine treatment for thyroid carcinoma

    International Nuclear Information System (INIS)

    Purpose: In thyroid cancer patients, radioiodine treatment has been shown to be associated with an increased risk of colon carcinoma. The aim of this study in thyroid cancer patients was to evaluate the role of familial factors in the risk of colorectal cancer and their potential interaction with radioiodine exposure. Methods and Materials: We performed a case-control study on 15 colorectal cancer patients and 76 matched control subjects, nested in a cohort of 3708 thyroid cancer patients treated between 1933 and 1998. For each patient, the radiation dose delivered to the colon by radioiodine was estimated by use of standard tables. In those who received external radiation therapy, the average radiation doses delivered to the colon and rectum were estimated by use of DOSEg software. A complete familial history was obtained by face-to-face interviews, and a familial index was defined to evaluate the degree of familial aggregation. Results: The risk of colorectal cancer increased with familial aggregation of colorectal cancer (p = 0.02). After adjustment for the radiation dose delivered to the colon and rectum, the risk of colorectal cancer was 2.8-fold higher (95% CI, 1.0-8.0) for patients with at least one relative affected by colorectal cancer than for patients without such a family history (p = 0.05). The radiation dose delivered to the colon and rectum by 131I and external radiation therapy was associated with an increase of risk near the significance threshold (p = 0.1). No significant interaction was found between radiation dose and having an affected relative (p = 0.9). Conclusions: The role of familial background in the risk of colorectal cancer following a differentiated thyroid carcinoma appears to increase with the radiation dose delivered to the colon and rectum. However, the study population was small and no interaction was found between these two factors

  19. Familial gastric cancer: detection of a hereditary cause helps to understand its etiology

    Directory of Open Access Journals (Sweden)

    Vogelaar Ingrid P

    2012-12-01

    Full Text Available Abstract Worldwide, gastric cancer is one of the most common forms of cancer, with a high morbidity and mortality. Several environmental factors predispose to the development of gastric cancer, such as Helicobacter pylori infection, diet and smoking. Familial clustering of gastric cancer is seen in 10% of cases, and approximately 3% of gastric cancer cases arise in the setting of hereditary diffuse gastric cancer (HDGC. In families with HDGC, gastric cancer presents at relatively young age. Germline mutations in the CDH1 gene are the major cause of HDGC and are identified in approximately 25-50% of families which fulfill strict criteria. Prophylactic gastrectomy is the only option to prevent gastric cancer in individuals with a CDH1 mutation. However, in the majority of families with multiple cases of gastric cancer no germline genetic abnormality can be identified and therefore preventive measures are not available, except for general lifestyle advice. Future research should focus on identifying new genetic predisposing factors for all types of familial gastric cancer.

  20. Breast and Ovarian Cancer and Family History Risk Categories

    Science.gov (United States)

    ... in one breast only) diagnosed after age 50 Grandmother with breast cancer diagnosed at age 75 Get ... breast cancer diagnosed at age 45 and paternal grandmother (father’s mother) with breast cancer diagnosed at age ...

  1. ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry

    OpenAIRE

    Anne-Laure Renault; Fabienne Lesueur; Yan Coulombe; Stéphane Gobeil; Penny Soucy; Yosr Hamdi; Sylvie Desjardins; Florence Le Calvez-Kelm; Maxime Vallée; Catherine Voegele; Hopper, John L.; Andrulis, Irene L.; Southey, Melissa C.; John, Esther M.; Jean-Yves Masson

    2016-01-01

    Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ...

  2. A social network analysis of communication about hereditary nonpolyposis colorectal cancer genetic testing and family functioning.

    Science.gov (United States)

    Koehly, Laura M; Peterson, Susan K; Watts, Beatty G; Kempf, Kari K G; Vernon, Sally W; Gritz, Ellen R

    2003-04-01

    Hereditary cancers are relational diseases. A primary focus of research in the past has been the biological relations that exist within the families and how genes are passed along family lines. However, hereditary cancers are relational in a psychosocial sense, as well. They can impact communication relationships within a family, as well as support relationships among family members. Furthermore, the familial culture can affect an individual's participation in genetic counseling and testing endeavors. Our aims are (a) to describe the composition of familial networks, (b) to characterize the patterns of family functioning within families, (c) to analyze how these patterns relate to communications about genetic counseling and testing among family members, and (d) to identify influential family members. Specifically, we asked how the relationship between mutation status, kinship ties, and family functioning constructs, e.g., communication, cohesion, affective involvement, leadership, and conflict, was associated with discussions about genetic counseling and testing. We used social network analysis and random graph techniques to examine 783 dyadic relationships in 36 members of 5 hereditary nonpolyposis colorectal cancer (HNPCC) families interviewed from 1999-2000. Results suggest that in these five HNPCC families, two family members are more likely to discuss genetic counseling and testing if either one carries the mutation, if either one is a spouse or a first-degree relative of the other, or if the relationship is defined by positive cohesion, leadership, or lack of conflict. Furthermore, the family functioning patterns suggest that mothers tend to be the most influential persons in the family network. Results of this study suggest encouraging family members who act in the mother role to take a "team approach" with the family proband when discussing HNPCC risks and management with family members.

  3. CHEK2 1100delC is prevalent in Swedish early onset familial breast cancer

    DEFF Research Database (Denmark)

    Margolin, Sara; Eiberg, Hans; Lindblom, Annika;

    2007-01-01

    763 breast cancer patients with a defined family history and 760 controls from the Stockholm region. The breast cancer patients originated from; a population-based cohort (n = 452) and from a familial cancer clinic (n = 311), the detailed family history was known in both groups. RESULTS: The variant......BACKGROUND: A truncating variant, 1100delC, in check point-kinase CHEK2, has been identified as a risk factor for familial and sporadic breast cancer. The prevalence in healthy non-breast cancer cases is low and varies between populations. METHODS: We analyzed the prevalence of CHEK2 1100delC in...... was found in 2.9% of the familial cases from the population-based cohort and in 1.9% from the familial cancer clinic. In total 2.2% of the patients with a family history of breast cancer carried the variant compared to 0.7% of the controls (p = 0.03). There was no increased prevalence in sporadic...

  4. Familial gastric cancers with Li-Fraumeni Syndrome: A case repast

    Institute of Scientific and Technical Information of China (English)

    Il-Jin Kim; Hio Chung Kang; Yong Shin; Byong Chul Yoo; Han-Kwang Yang; Jae-Gahb Park

    2005-01-01

    @@ TO THE EDITOR Although the incidence of gastric cancer has declined somewhat in recent years, it remains one of the most common cancers worldwide[1], and is the most common cancer in East Asian countries such as Korea and Japan[2].In terms of the genetics of gastric cancer, mutations in CDH1 (E-cadberin) have been associated with hereditary diffuse gastric cancer (HDGC). The first germline mutation in CDH1 was reported in a large Maori HDGC family[1],with subsequent corroborations in Western and Asian HDGC families[3-5], CDH1 mutations are believed to be associated with up to 50% of HDGC families[5], but have not been linked with sporadic or intestinal types of gastric cancer[5].

  5. A Study Of The Effects Of Illness Experienced By Families Of Oral And Oropharyngeal Cancer Patients

    Directory of Open Access Journals (Sweden)

    Bhagyalaxmi A

    2002-01-01

    Full Text Available Research question : What are the various areas and burden a family experiences due to presence of oral and oropharyngeal cancer patient. Objectives: 1. To identify the family burden like financial burden, disruption of routine activities and family leisure etc. 2. To study the severity of family burden experienced by the families of oral and oropharyngeal cancer patients. Study design: Case- control. Setting: Gujarat Cancer and Research Institute (G.C.R.I, Ahmedabad. Participants: 100 cases belonging to the diagnostic categories no. 140-46 of ICD â€"9 and 100 controls belonging to the diagnostic categories other than no. 140-46 of ICD-9 Statistical analysis: Proportions, Chi-square test and Z test. Results: Financial burden was observed in 36% of cases and 43% of controls had burden on the family. Out of 43% respondents reporting any burden, 36(83.72% were identified with severe burden.

  6. Family Matters: Adjustment to genetic cancer susceptibility testing

    NARCIS (Netherlands)

    I.I.H. van Oostrom (Iris)

    2006-01-01

    textabstractCancer is generally feared because it is associated with death and severe physical suffering. It is one of the most common causes of death in the Netherlands. Breast and colon cancer are the most prevalent types of cancer among women. Frequently occurring types in men are cancer of colon

  7. Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.

    Science.gov (United States)

    Piccolo, Stephen R; Hoffman, Laura M; Conner, Thomas; Shrestha, Gajendra; Cohen, Adam L; Marks, Jeffrey R; Neumayer, Leigh A; Agarwal, Cori A; Beckerle, Mary C; Andrulis, Irene L; Spira, Avrum E; Moos, Philip J; Buys, Saundra S; Johnson, William Evan; Bild, Andrea H

    2016-03-01

    The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic risk variants, known risk variants account for at most 30% of FBC cases. Considering that multiple genes may influence FBC risk, we hypothesized that a pathway-based strategy examining different data types from multiple tissues could elucidate the biological basis for FBC. In this study, we performed integrated analyses of gene expression and exome-sequencing data from peripheral blood mononuclear cells and showed that cell adhesion pathways are significantly and consistently dysregulated in women who develop FBC. The dysregulation of cell adhesion pathways in high-risk women was also identified by pathway-based profiling applied to normal breast tissue data from two independent cohorts. The results of our genomic analyses were validated in normal primary mammary epithelial cells from high-risk and control women, using cell-based functional assays, drug-response assays, fluorescence microscopy, and Western blotting assays. Both genomic and cell-based experiments indicate that cell-cell and cell-extracellular matrix adhesion processes seem to be disrupted in non-malignant cells of women at high risk for FBC and suggest a potential role for these processes in FBC development. PMID:26969729

  8. Role of the Family Physician in the Care of Cancer Patients

    OpenAIRE

    McWhinney, Ian R.; Hoddinott, Susan N.; Bass, Martin J.; Gay, Keith; Shearer, Robin

    1990-01-01

    To assess the involvement of family physicians in the continuing care of cancer patients, 499 patients attending the London Regional Cancer Centre for follow-up appointments were questioned. Of the 493 patients with a family doctor, 282 (57.2%) reported that their family doctor had been involved in the diagnosis, 132 (26.8%) in the treatment, and 214 (43.4%) in the follow up. Only 60% thought that their family doctor was aware of their current problems, and only 31.4% had an appointment to se...

  9. The influence of family history on prostate cancer risk: implications for clinical management.

    Science.gov (United States)

    Madersbacher, Stephan; Alcaraz, Antonio; Emberton, Mark; Hammerer, Peter; Ponholzer, Anton; Schröder, Fritz H; Tubaro, Andrea

    2011-03-01

    • The most recent evidence for the link between a family history of prostate cancer and individual risk for future disease was examined, with the aim of understanding what the existence and nature of a family history of prostate cancer does to a man's risk of developing the disease. • Our findings highlighted the clear association between a family history of prostate cancer and increased risk of developing the disease; with a greater proximity of relatedness, greater number of family members affected and/or earlier age at diagnosis of the family member elevating risk further. • These findings have important clinical implications for the identification and subsequent management of men deemed to be at increased risk of developing prostate cancer. The evidence for prostate cancer risk reduction with the mono 5α-reductase inhibitor (5ARI) finasteride in a low-risk population and, more recently, with the dual 5ARI dutasteride in a population at increased risk of developing the disease, has potential to expand management options for men at risk of developing prostate cancer beyond more frequent and/or earlier surveillance. • Given that family history can be easily assessed in routine clinical practice, it should be regarded as an important parameter to consider alongside PSA level for prostate cancer risk assessment. PMID:21166744

  10. Predictors of Self-Reported Family Health History of Breast Cancer.

    Science.gov (United States)

    Ricks-Santi, Luisel J; Thompson, Nicole; Ewing, Altovise; Harrison, Barbara; Higginbotham, Kimberly; Spencer, Cherie; Laiyemo, Adeyinka; DeWitty, Robert; Wilson, Lori; Horton, Sara; Dunmore-Griffith, Jacqueline; Williams, Carla; Frederick, Wayne

    2016-10-01

    The objective of this study was to identify predictors of self-reported family health history of breast cancer in an ethnically diverse population of women participating in a breast cancer screening program. Participants completed a self-administered questionnaire about their demography, health, breast health and family health history of breast cancer. The association between family health history of breast cancer and categorical variables were analyzed using the T test, chi square, and multi-nominal logistic regression. Those who were least likely to report a family history of cancer were African Americans (p = 0.02), and immigrant women from South America (p Africa (p = 0.04). However, 34.4 % reported having a second-degree maternal relative with breast cancer compared to 6.9 % who reported having a second degree paternal relative with breast cancer. Therefore, there is a need to increase efforts to educate families about the importance of collecting and sharing one's family health history. PMID:26201692

  11. Prospective surveillance of women with a family history of breast cancer: auditing the risk threshold

    Science.gov (United States)

    Anderson, E; Berg, J; Black, R; Bradshaw, N; Campbell, J; Carnaghan, H; Cetnarkyj, R; Drummond, S; Davidson, R; Dunlop, J; Fordyce, A; Gibbons, B; Goudie, D; Gregory, H; Holloway, S; Longmuir, M; McLeish, L; Murday, V; Miedzybrodska, Z; Nicholson, D; Pearson, P; Porteous, M; Reis, M; Slater, S; Smith, K; Smyth, E; Snadden, L; Steel, M; Stirling, D; Watt, C; Whyte, C; Young, D

    2008-01-01

    To evaluate current guidelines criteria for inclusion of women in special ‘breast cancer family history' surveillance programmes, records were reviewed of women referred to Scottish breast cancer family clinics between January 1994 and December 2003 but discharged as at ‘less than ‘moderate' familial risk'. The Scottish Cancer Registry was then interrogated to determine subsequent age-specific incidence of breast cancer in this cohort and corresponding Scottish population figures. Among 2074 women, with an average follow-up of 4.0 years, 28 invasive breast cancers were recorded up to December 2003, where 14.4 were expected, a relative risk (RR) of 1.94. Eleven further breast cancers were recorded between January 2004 and February 2006 (ascertainment incomplete for this period). The overall RR for women in the study cohort exceeded the accepted ‘cutoff' level (RR=1.7) for provision of special counselling and surveillance. The highest RR was found for the age group 45–59 years and this group also generated the majority of breast cancers. The National Institute for Clinical Excellence (‘NICE') guidelines appear to be more accurate than those of the Scottish Intercollegiate Guidelines Network (‘SIGN') in defining ‘moderate' familial risk, and longer follow-up of this cohort could generate an evidence base for further modification of familial breast cancer services. PMID:18283300

  12. Plasma Protein Carbonyls and Breast Cancer Risk in Sisters Discordant for Breast Cancer from the New York Site of the Breast Cancer Family Registry

    OpenAIRE

    Zipprich, Jennifer; Terry, Mary Beth; Liao, Yuyan; Agrawal, Meenakshi; Gurvich, Irina; Senie, Ruby; Santella, Regina M.

    2009-01-01

    Reactive Oxygen Species (ROS) are important in the pathogenesis of many diseases, including breast cancer. Several population-based case-control studies have demonstrated that various biomarkers of oxidative stress are associated with an increase in breast cancer risk. We selected sisters discordant for breast cancer (n=645) from the New York site of the Breast Cancer Family Registry to explore factors that contribute to variation in plasma protein carbonyls, and to determine whether this bio...

  13. Mutation Analysis in the BRCA1 Gene in Chinese Breast Cancer Families

    Institute of Scientific and Technical Information of China (English)

    WUZhengyan; ZHENLinlin; FANPing

    2003-01-01

    Objective: To study the mutation of BRCA1 gene in Chinese breast cancer families. Methods:Fifteen families were selected, involving 41 members, consisting of 23 breast cancer patients. Using poly-merase chain reaction and single stranded conformation polymorphism (PCR-SSCP), and subsequent DNA sequencing, the mutation of BRCA1 genes were analyzed. Results: Four mutations were found in all fam-ilies, and the proportion of mutation was 26.7% (4/15) in breast cancer families. One of the 4 mutations was 2228 insC, resulting in chain termination at codon 711. The remaining 3 mutations were 1884A→T and 3232A→G, resulting in single amino acid change respectively. Conclusion: BRCA1 is a breast cancer susceptibility gene. The relatively low proportion and frequency of BRCA1 mutations in our study hints additional BRCA genes existed.

  14. Family Caregivers in Cancer: Roles and Challenges (PDQ®)—Health Professional Version

    Science.gov (United States)

    Expert-reviewed information summary about the challenges faced by family caregivers of cancer patients. This summary focuses on typical caregiver roles and concerns, and helpful interventions for caregivers.

  15. Obesity in post menopausal women with a family history of breast cancer: prevalence and risk awareness

    OpenAIRE

    Begum, Parvin; Richardson, Caroline E; Carmichael, Amtul R.

    2009-01-01

    Background: Obesity and physical activity are modifiable risk factors in the development of postmenopausal breast cancer. The aim of this study was to assess the level of awareness and prevalence of these factors in women attending family history clinics. Methods: Women attending the breast cancer family history clinic from 2004 to 2006 completed a questionnaire (SP15 format) about their knowledge of and exposure to various diet and lifestyle factors. All women had been counselled by a Co...

  16. Primary care physicians' use of family history for cancer risk assessment

    OpenAIRE

    Stockdale Alan; Ashikaga Takamaru; Wood Marie E; Flynn Brian S; Dana Greg S; Naud Shelly

    2010-01-01

    Abstract Background Family history (FH) assessment is useful in identifying and managing patients at increased risk for cancer. This study assessed reported FH quality and associations with physician perceptions. Methods Primary care physicians practicing in two northeastern U.S. states were surveyed (n = 880; 70% response rate). Outcome measures of FH quality were extent of FH taken and ascertaining age at cancer diagnosis for affected family members. Predictors of quality measured in this s...

  17. Risk factors for colorectal cancer in subjects with family history of the disease.

    OpenAIRE

    Fernandez, E.; La Vecchia, C.; D'Avanzo, B; De Negri, E.; Franceschi, S

    1997-01-01

    The relationship between lifestyle factors, past medical conditions, daily meal frequency, diet and the risk of 'familial' colorectal cancer has been analysed using data from a case-control study conducted in northern Italy. A total of 1584 colorectal cancer patients and 2879 control subjects were admitted to a network of hospitals in the Greater Milan area and the Pordenone province. The subjects included for analysis were the 112 cases and the 108 control subjects who reported a family hist...

  18. The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers

    OpenAIRE

    Friedenson Bernard

    2007-01-01

    Abstract Background The present study was designed to test the hypothesis that inactivation of virtually any component within the pathway containing the BRCA1 and BRCA2 proteins would increase the risks for lymphomas and leukemias. In people who do not have BRCA1 or BRCA2 gene mutations, the encoded proteins prevent breast/ovarian cancer. However BRCA1 and BRCA2 proteins have multiple functions including participating in a pathway that mediates repair of DNA double strand breaks by error-free...

  19. Cancer and Anorexia Nervosa in the Adolescence: A Family-Based Systemic Intervention

    Directory of Open Access Journals (Sweden)

    Gabriella De Benedetta

    2011-01-01

    Full Text Available Objective. Anorexia nervosa is difficult to diagnose in cancer patients since weight loss, aversion for food, and eating disturbances are frequent in patients undergoing chemotherapy and radiotherapy. Nevertheless, efforts are mandatory to recognize and manage this condition which may occur also in cancer patients with a special regard to adolescents. Methods. Through the clinical history of Anna, a 15-year-old adolescent with advanced cancer, we describe the effectiveness of a family-based systemic intervention to manage anorexia nervosa occurring in concomitance to osteosarcoma. Results. Through a two-year psychotherapy period involving different techniques applied to the whole family such as family genogram, family collage, and sculpture of family time, Anna was relieved from her condition. Conclusions. Upon early diagnosis and appropriate treatment, anorexia nervosa can be effectively approached in adolescent cancer patients. The presence of a life-threatening medical condition such as cancer may provide motivation for a patient to control disordered eating behavior in the context of an appropriate family-based systemic intervention. The general frame of anorexia occurring in cancer-bearing adolescents is reviewed and discussed.

  20. Genome-wide sequencing to identify the cause of hereditary cancer syndromes: with examples from familial pancreatic cancer.

    Science.gov (United States)

    Roberts, Nicholas J; Klein, Alison P

    2013-11-01

    Advances in our understanding of the human genome and next-generation technologies have facilitated the use of genome-wide sequencing to decipher the genetic basis of Mendelian disease and hereditary cancer syndromes. However, the application of genome-wide sequencing in hereditary cancer syndromes has had mixed success, in part, due to complex nature of the underlying genetic architecture. In this review we discuss the use of genome-wide sequencing in both Mendelian diseases and hereditary cancer syndromes, highlighting the potential and challenges of this approach using familial pancreatic cancer as an example. PMID:23196058

  1. 'Cancer doesn't have an age': genetic testing and cancer risk management in BRCA1/2 mutation-positive women aged 18-24.

    Science.gov (United States)

    Werner-Lin, Allison; Hoskins, Lindsey M; Doyle, Maya H; Greene, Mark H

    2012-11-01

    Increasingly, 18-24-year-old women from hereditary breast/ovarian cancer (HBOC) families are pursuing genetic testing, despite their low absolute risks of breast and ovarian cancer and the fact that evidence-based management options used with older high-risk women are not generally available. Difficult clinical decisions in older carriers take on substantially more complexity and value-laden import in very young carriers. As a result, many of the latter receive highly personal and emotionally charged cancer risk information in a life context where management strategies are not well defined. We analyzed 32 in-depth interviews with BRCA1/2 mutation-positive women aged 18-24 using techniques of grounded theory and interpretive description. Participants described feeling vulnerable to a cancer diagnosis but in a quandary regarding their care because evidence-based approaches to management have not been developed and clinical trials have not been undertaken. Our participants demonstrated a wide range of genetic and health literacy. Inconsistent recommendations, surveillance fatigue, and the unpredictability of their having health insurance coverage for surgical risk-reducing procedures led several to contemplate risk-reducing mastectomy before age 25. Parents remained a primary source of emotional and financial support, slowing age-appropriate independence and complicating patient privacy. Our findings suggest that, for 18-24-year-olds, readiness to autonomously elect genetic testing, to fully understand and act on genetic information, and to confidently make decisions with life-long implications are all evolving processes. We comment on the tensions between informed consent, privacy, and the unique developmental needs of BRCA1/2 mutation-positive women just emerging into their adult years. PMID:22547552

  2. [Usefulness of the oncogenetic molecular counselling in adults whith familial cancer].

    Science.gov (United States)

    Valdespino-Gómez, Víctor M; Valdespino-Castillo, Víctor E

    2016-01-01

    More than 200 cancer susceptibility syndromes (CSS) have been recognized through performing classic epidemiologic studies and genetic linkage analysis. In most CSSs clinical conditions of the patients have been identified as well as their hereditary patterns and the predisponent genes to cancer development. Cancer hereditary identification is a useful condition, since cancer family integrants may benefit of efficient strategies in early screening and in tumor prevention strategies; this consultation is performed by oncogenetic molecular medical consultants who must be scientifically competent for Human Genetics and Cancer molecular biology domains. The oncogenetic molecular consult of patients and family relatives of cancer predisposition families is a medical service in health programs of developed and developing countries; in our country this type of medical service needs to be organized and settled to be part of the integral oncology medical service. The oncogenetic molecular consultation is a structural process of assessment and communication of the associated integral problems of the cancer inherited susceptibility in familial cancer. PMID:27100983

  3. Women worried about their familial breast cancer risk - A study on genetic advice in general practice

    NARCIS (Netherlands)

    de Bock, GH; Perk, DC; Oosterwijk, JC; Hageman, GCHA; Kievit, J; Springer, MP

    1997-01-01

    Aims. To ascertain whether women who consulted their GP because they perceived themselves as at increased risk of familial breast cancer were indeed at increased risk, and to evaluate potential strategies for assessing genetic risk of breast cancer in general practice. Methods. Sixty-seven out of 81

  4. The influence of family history on prostate cancer risk : implications for clinical management

    NARCIS (Netherlands)

    Madersbacher, Stephan; Alcaraz, Antonio; Emberton, Mark; Hammerer, Peter; Ponholzer, Anton; Schroeder, Fritz H.; Tubaro, Andrea

    2011-01-01

    A family history of prostate cancer has long been identified as an important risk factor for developing the disease. This risk factor can be easily assessed in clinical practice and current guidelines recommend to initiate prostate cancer early detection 5 years earlier (i.e. around the age of 40 ye

  5. The impact of parental cancer on children and the family : a review of the literature

    NARCIS (Netherlands)

    Visser, A; Huizinga, GA; van der Graaf, WTA; Hoekstra, HJ; Hoekstra-Weebers, JEHM

    2004-01-01

    Objective. Children of cancer patients may go through a distressing time. The aim of this review was to survey present knowledge on the impact of parental cancer on children and the family. Design. Studies published between January 1980 and March 2004 addressing emotional, social, behavioural, cogni

  6. Risk of thyroid cancer in euthyroid asymptomatic patients with thyroid nodules with an emphasis on family history of thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    JHwang, Shin Hye; Kim, Eun Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kwak, Jin Young [Dept. of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-04-15

    To determine the factors associated with thyroid cancer, focusing on first-degree family history and ultrasonography (US) features, in euthyroid asymptomatic patients with thyroid nodules. This retrospective study included 1310 thyroid nodules of 1254 euthyroid asymptomatic patients who underwent US-guided fine-needle aspiration biopsy between November 2012 and August 2013. Nodule size and clinical risk factors- such as patient age, gender, first-degree family history of thyroid cancer, multiplicity on US and serum thyroid stimulating hormone (TSH) levels - were considered together with US features to compare benign and malignant nodules. Multiple logistic regression analysis was performed to assess the risk of thyroid malignancy according to clinical and US characteristics. Although all of the clinical factors and US findings were significantly different between patients with benign and malignant nodules, a solitary lesion on US (p = 0.041–0.043), US features and male gender (p < 0.001) were significant independent risk factors for thyroid malignancy in a multivariate analysis. Patient age, a first-degree family history of thyroid cancer and high normal serum TSH levels did not independently significantly increase the risk of thyroid cancer. However, multicollinearity existed between US assessment and patient age, first-degree family history of thyroid cancer and serum TSH values. Ultrasonography findings should be the primary criterion used to decide the management of euthyroid asymptomatic patients with thyroid nodules. The concept of first-degree family history as a risk factor for thyroid malignancy should be further studied in asymptomatic patients.

  7. Family Support, Age, and Emotional States of Terminally Ill Cancer Patients.

    Science.gov (United States)

    Wu, Kitty K. Y.

    1991-01-01

    Explored emotional states of dying patients, age, and family support. Findings from 26 terminally ill female cancer patients revealed that younger patients expressed more bargaining and complaints than older patients who revealed more depression and acceptance. Patients with immediate family support expressed less depression and more fears than…

  8. Candidate colorectal cancer predisposing gene variants in Chinese early-onset and familial cases

    NARCIS (Netherlands)

    Zhang, J.X.; Fu, L.; Voer, R.M. de; Hahn, M.M.; Jin, P.; Lv, C.X.; Verwiel, E.T.; Ligtenberg, M.J.L.; Hoogerbrugge, N.; Kuiper, R.P.; Sheng, J.Q.; Geurts van Kessel, A.H.M.

    2015-01-01

    AIM: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer (CRC) predisposing genes in early-onset or familial CRC cases. METHODS: We performed whole-exome sequencing in 23 Chinese patients from 21 families with non-polyposis CRC

  9. Family functioning and adolescents' emotional and behavioral problems : when a parent has cancer

    NARCIS (Netherlands)

    Gazendam-Donofrio, S.M.; Hoekstra, H.J.; van der Graaf, W.T.A.; van de Wiel, H.B.; Visser, A.; Huizinga, G.A.; Hoekstra-Weebers, J.E.

    2007-01-01

    Background: This article focuses on possible relationships between functioning of adolescents with a parent diagnosed with cancer 1-5 years earlier and family environment. Patients and methods: In all, 138 patients, 114 spouses and 221 adolescents completed the Family Environment Scale. Additionally

  10. Moving to place: childhood cancer treatment decision making in single-parent and repartnered family structures.

    Science.gov (United States)

    Kelly, Katherine Patterson; Ganong, Lawrence

    2011-03-01

    Few researchers have studied how parents from diverse family structures cope with childhood chronic illness. We designed this study to discern the childhood cancer treatment decision-making (TDM) process in these families. Using grounded theory, we interviewed 15 custodial parents, nonresidential parents, and stepparents who had previously made a major treatment decision for their children with cancer. "Moving to place" was the central psychosocial process by which parents negotiated involvement in TDM. Parents moved toward or were moved away from involvement based on parent position in the family (custodial, nonresidential, and stepparent), prediagnosis family dynamics, and time since diagnosis. Parents used the actions of stepping up, stepping back, being pushed, and stepping away to respond to the need for TDM. Parents faced additional stressors because of their family situations, which affected the TDM process. Findings from this study provide important insight into diverse families and their unique parental TDM experiences.

  11. PARENTAL TYPE OF PERSONALITY, NEGATIVE AFFECTIVITY AND FAMILY STRESSFUL EVENTS IN CHILDREN WITH CANCER

    OpenAIRE

    Jakovljević, Gordana; Čulić, Srđana; Benko, Marta; Kalebić Jakupčević, Katja; Stepan, Jasminka; Šprajc, Mirjana

    2010-01-01

    Objective: Psychological interactions between parents,children and social environment are very important for childhood health. The type of personality and stressful events are probably also cancer risk factors. We investigated personality types A/B and D (negative affectivity and social inhibition) in parents of children with cancer (PCC), as well as social environmental factors, and family / children’s stressful events before the appearance of cancer. Subjects and methods: Bortne...

  12. Psychological distress among family carers of oesophageal cancer survivors the role of illness cognitions and coping

    OpenAIRE

    Dempster, Martin; McCorry, Noleen; Brennan, Emma; Donnelly, Michael; Murray, Liam,; Johnston, Brian T.

    2011-01-01

    Objective: The research aimed to determine the extent to which illness cognitions and coping explain psychological distress (fear of cancer recurrence, anxiety and depression symptoms) among family carers of survivors of oesophageal cancer.Methods: Carers of patients registered with the Oesophageal Patients' Association in the UK were mailed a questionnaire booklet containing questions about medical and demographic variables, the Illness Perception Questionnaire-Revised, the Cancer Coping Que...

  13. Cancer and Anorexia Nervosa in the Adolescence: A Family-Based Systemic Intervention

    OpenAIRE

    Gabriella De Benedetta; Ida Bolognini; Silvia D'Ovidio; Antonello Pinto

    2011-01-01

    Objective. Anorexia nervosa is difficult to diagnose in cancer patients since weight loss, aversion for food, and eating disturbances are frequent in patients undergoing chemotherapy and radiotherapy. Nevertheless, efforts are mandatory to recognize and manage this condition which may occur also in cancer patients with a special regard to adolescents. Methods. Through the clinical history of Anna, a 15-year-old adolescent with advanced cancer, we describe the effectiveness of a family-based s...

  14. Genomic DNA copy-number alterations of the let-7 family in human cancers.

    Directory of Open Access Journals (Sweden)

    Yanling Wang

    Full Text Available In human cancer, expression of the let-7 family is significantly reduced, and this is associated with shorter survival times in patients. However, the mechanisms leading to let-7 downregulation in cancer are still largely unclear. Since an alteration in copy-number is one of the causes of gene deregulation in cancer, we examined copy number alterations of the let-7 family in 2,969 cancer specimens from a high-resolution SNP array dataset. We found that there was a reduction in the copy number of let-7 genes in a cancer-type specific manner. Importantly, focal deletion of four let-7 family members was found in three cancer types: medulloblastoma (let-7a-2 and let-7e, breast cancer (let-7a-2, and ovarian cancer (let-7a-3/let-7b. For example, the genomic locus harboring let-7a-3/let-7b was deleted in 44% of the specimens from ovarian cancer patients. We also found a positive correlation between the copy number of let-7b and mature let-7b expression in ovarian cancer. Finally, we showed that restoration of let-7b expression dramatically reduced ovarian tumor growth in vitro and in vivo. Our results indicate that copy number deletion is an important mechanism leading to the downregulation of expression of specific let-7 family members in medulloblastoma, breast, and ovarian cancers. Restoration of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of cancer.

  15. Ovarian cancer in BRCA1/2 mutation carriers : The impact of mutation position and family history on the cancer risk

    NARCIS (Netherlands)

    Teixeira, Natalja; Mourits, Marian J. E.; Vos, Janet R.; van der Kolk, Donna M.; Jansen, Liesbeth; Oosterwijk, Jan; de Bock, Geertruida H.

    2015-01-01

    Objectives: Assessing the combined impact of mutation position, regarding the ovarian cancer cluster region (OCCR), and type of cancer family history (FH) on age-related penetrance of ovarian cancer (OC) in women from BRCA/2 families from the northern Netherlands. Study design: A consecutive series

  16. Features of 152 families eligible for the investigation of mutations in BRCA1 / 2, evaluated Onco genetics unit Clinics Hospital

    International Nuclear Information System (INIS)

    Full text: The aim of this study is to contribute to the characterization of familial breast cancer in our country. Patients and methods. We analyzed 152 families referred to the Hospital Unit Onco genetics Clinic, who had 3 or more cases of breast cancer (C M)(at least one diagnosed before age 50 years) (n = 92)or 2 cases with some sub-criterion (paternal transmission, C M bilateral C M male, ovarian cancer (O C), Ashkenazi Jewish ancestry, a case diagnosed before 40 years) (n = 47)or 4 or more cases without regard to age at diagnosis (n = 4)or an single case diagnosed before age 35 (n = 9). The clinical data collection was conducted onco genetics the query was entered in which, among others, the presence or absence of nongenetic risk factors, personal and family history of breast, ovarian and other tumors and age of diagnosis. Results. 152 cases were selected indices, carrying 148 C M (bilateral n = 29)and 4 CO. The median age at diagnosis of C M developed in these patients was 48 years (range: 25-54). Twenty-three of the 151 patients had a second tumor extra mammary (ovary n = 7; melanoma n = 2, n = 3 cervix, colon n = 4, n = 1 sarcoma, ENT = 1, = 1 pancreas, kidney = 2, CBP = 1, esophagus = 1). Among the relatives of the relevant parent branch were 329 C M (25 bilateral, 2 male)diagnosed before 50 years in more than 60 % of cases and 22 ovarian cancers. Comparing the frequency of different tumor locations both branches parents. In the relevant parent branch, and the prevalence of C M and CO documented a higher frequency of prostate, stomach, pancreas and melanoma. It was possible to obtain information He r2 tumor expression, estrogen receptor (E R) and progesterone receptor (P R) in 25 patients, finding that 10 patients (0.40)had He r2 overexpression, 11 (0.46 R E and / / or P R positive, HER2 negative and 4 E R, P R and He r2 negative (0.16). Conclusions. The characteristics of the families studied, including the frequency of tumors extramamarios agrees with

  17. Why are reproductive cancers more common in nulliparous women?

    Science.gov (United States)

    Gleicher, Norbert

    2013-05-01

    It has been known for decades that nulliparity is associated with an increased risk for certain reproductive malignancies, including breast, ovarian and uterine cancers. A recent commentary in The Lancet summarized the available evidence based on data in nulliparous women and concluded that the risk of nulliparity was related to the increased number of ovulatory cycles, and so might be preventable by utilization of oral contraceptives. That communication described significant differences in age-dependent cancer mortality in nulliparous nuns, as well as in parous controls, between breast, ovarian and uterine cancers. Moreover, the steep inclines in cancer mortality in nuns are only observed decades after the menopause. Taken together, these observations make it appear unlikely that the number of ovulations is associated aetiologically with increased cancer risks in nulliparous nuns. Here are postulated other possible primary mechanisms that could be responsible for the reported age-related increase in cancer risks in nulliparous women, such as nuns, and conclude that a better understanding of such mechanisms may offer important new insights into tumour initiation in general. PMID:23518034

  18. Expression of the EGF Family in Gastric Cancer

    DEFF Research Database (Denmark)

    Nielsen, Trine Ostergaard; Friis-Hansen, Lennart; Poulsen, Steen Seier;

    2014-01-01

    Gastric cancer is a major cause of cancer-related deaths in both men and women. The epidermal growth factor receptors are EGFR, HER2, HER3 and HER4. Of the four epidermal growth factor receptors, EGFR and HER2 are well-known oncogenes involved in gastric cancer. Little, however, is known about...... the role played by HER3 and HER4 in this disease. We obtained paired samples from the tumor and the adjacent normal tissue from the same patient undergoing surgery for gastric cancer. Using RT-qPCR, we quantified the mRNA expression of the four receptors including the HER4 splicing isoforms and all....... These results support the involvement of EGFR and HER2 in gastric cancer and suggest an interesting association of reduced HER4 expression with development of gastric cancer....

  19. Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families

    Institute of Scientific and Technical Information of China (English)

    Xu-Lin Wang; Ying Yuan; Su-Zhan Zhang; Shan-Rong Cai; Yan-Qin Huang; Qiang Jiang; Shu Zheng

    2006-01-01

    AIM: To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands.METHODS: Thirty-one independent Chinese HNPCC families were collected in Zhejiang Province. All of them met Chinese HNPCC criteria. Clinical data about patient gender, site of colorectal cancer, age of onset, history of multiple colorectal cancer, associated extracolonic cancer were recorded. PCR and denaturing high performance liquid chromatography (DHPLC) were employed to screen the mutations. Sequencing analysis was used to find out the exact mutation site and characteristics of the samples showing abnormal DHPLC profiles.RESULTS: One hundred and thirty-six malignant neoplasms were found in 107 patients including 14 multiple cancers. One hundred and six of the 136 neoplasms (77.9%) were diagnosed as colorectal cancer, with an average age of onset at 48.57 ± 29.00 years. Gastric cancer was the most common extracolonic cancer (10.3%) in these families. Twenty-three different sequence variations in hMLH1 and hMSH2 genes were detected in these 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations. The latter seven mutations seemed to be pathogenic.CONCLUSION: Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some particular clinical characteristics, such as a left-sided predominance, less synchronous or metachronous colorectal cancer, and frequent occurrence of gastric cancer.

  20. Birth order, family size, and the risk of cancer in young and middle-aged adults

    OpenAIRE

    K. Hemminki; Mutanen, P

    2001-01-01

    We used the Swedish Family-Cancer Database to analyse the effects of birth order and family size on the risk of common cancers among offspring born over the period 1958–96. Some 1.38 million offspring up to age 55 years with 50.6 million person-years were included. Poisson regression analysis included age at diagnosis, birth cohort, socio-economic status and region of residence as other explanatory variables. The only significant associations were an increasing risk for breast cancer by birth...

  1. Early-life family structure and microbially induced cancer risk.

    OpenAIRE

    Martin J Blaser; Abraham Nomura; James Lee; Stemmerman, Grant N; Perez-Perez, Guillermo I

    2007-01-01

    Editors' Summary Background. Although the theory that certain cancers might be caused by infectious agents (such as bacteria and viruses) has been around for some time, concrete evidence linking specific cancers and infections is only recently beginning to emerge. There is now very good evidence that stomach cancer, once one of the frequent types worldwide but now less common, is strongly associated with a particular infection of the stomach lining. This specific bacterium colonizing the stom...

  2. Epidemiological trends of hormone-related cancers in Slovenia.

    Science.gov (United States)

    Zadnik, Vesna; Krajc, Mateja

    2016-06-01

    The incidence of hormone-related cancers tends to be higher in the developed world than in other countries. In Slovenia, six hormone-related cancers (breast, ovarian, endometrial, prostate, testicular, and thyroid) account for a quarter of all cancers. Their incidence goes up each year, breast and prostate cancer in particular. The age at diagnosis is not decreasing for any of the analysed cancer types. The risk of breast cancer is higher in the western part of the country, but no differences in geographical distribution have been observed for other hormone-related cancers. Furthermore, areas polluted with endocrine-disrupting chemicals that affect hormone balance such as PCBs, dioxins, heavy metals, and pesticides, do not seem to involve a greater cancer risk. We know little about how many cancers can be associated with endocrine disruptors, as there are too few reliable exposure studies to support an association. PMID:27331295

  3. Family history of cancer in benign brain tumor subtypes versus gliomas

    Directory of Open Access Journals (Sweden)

    Quinn eOstrom

    2012-02-01

    Full Text Available Purpose: Family history is associated with gliomas, but this association has not ben established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study (OBTS. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%, 78 meningioma (65%, 49 pituitary adenoma (73.1% and 152 glioma patients (58.2%. The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs and 95% confidence intervals (95% CI. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusions: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  4. Molecular classification of familial non-BRCA1/BRCA2 breast cancer.

    Science.gov (United States)

    Hedenfalk, Ingrid; Ringner, Markus; Ben-Dor, Amir; Yakhini, Zohar; Chen, Yidong; Chebil, Gunilla; Ach, Robert; Loman, Niklas; Olsson, Håkan; Meltzer, Paul; Borg, Ake; Trent, Jeffrey

    2003-03-01

    In the decade since their discovery, the two major breast cancer susceptibility genes BRCA1 and BRCA2, have been shown conclusively to be involved in a significant fraction of families segregating breast and ovarian cancer. However, it has become equally clear that a large proportion of families segregating breast cancer alone are not caused by mutations in BRCA1 or BRCA2. Unfortunately, despite intensive effort, the identification of additional breast cancer predisposition genes has so far been unsuccessful, presumably because of genetic heterogeneity, low penetrance, or recessive/polygenic mechanisms. These non-BRCA1/2 breast cancer families (termed BRCAx families) comprise a histopathologically heterogeneous group, further supporting their origin from multiple genetic events. Accordingly, the identification of a method to successfully subdivide BRCAx families into recognizable groups could be of considerable value to further genetic analysis. We have previously shown that global gene expression analysis can identify unique and distinct expression profiles in breast tumors from BRCA1 and BRCA2 mutation carriers. Here we show that gene expression profiling can discover novel classes among BRCAx tumors, and differentiate them from BRCA1 and BRCA2 tumors. Moreover, microarray-based comparative genomic hybridization (CGH) to cDNA arrays revealed specific somatic genetic alterations within the BRCAx subgroups. These findings illustrate that, when gene expression-based classifications are used, BRCAx families can be grouped into homogeneous subsets, thereby potentially increasing the power of conventional genetic analysis.

  5. Familial gastric cancer : guidelines for diagnosis, treatment and periodic surveillance

    NARCIS (Netherlands)

    Kluijt, Irma; Sijmons, Rolf H.; Hoogerbrugge, Nicoline; Plukker, John T.; de Jong, Daphne; van Krieken, J. Han; van Hillegersberg, Richard; Ligtenberg, Marjolijn; Bleiker, Eveline; Cats, Anemieke

    2012-01-01

    Hereditary diffuse gastric cancer (HDGC) is a relatively rare disorder, with a mutated CDH1 gene as the only known cause. Carriers of a germline mutation in CDH1 have a lifetime risk of > 80% of developing diffuse gastric cancer. As periodic gastric surveillance is of limited value in detecting earl

  6. [Familial gastric cancer: diagnosis, treatment and periodic surveillance

    NARCIS (Netherlands)

    Kluijt, I.; Sijmons, R.H.; Hoogerbrugge, N.; Vasen, H.F.; Cats, A.

    2011-01-01

    The only known genetic causes of hereditary diffuse gastric cancer (HDGC) are germline mutations in the CDH1 gene.- CDH1 mutation carriers have a lifetime risk of 70-80% of developing diffuse gastric cancer. As periodic gastric surveillance is of limited value in detecting early stages of HDGC, prop

  7. Breast Cancer Screening in Women with Hereditary or Familial Risk

    NARCIS (Netherlands)

    S. Saadatmand (Sepideh)

    2015-01-01

    markdownabstract__Abstract__ We estimated influence of tumor size and number of positive lymph nodes at breast cancer detection on survival in the current era of new system (neo) adjuvant therapies. We showed that early breast cancer detection remains of great influence. Relative 5-year survival wa

  8. Health Information Needs of Childhood Cancer Survivors and Their Family

    NARCIS (Netherlands)

    S.L. Knijnenburg; L.C. Kremer; C. Bos; K.I. Braam; M.W.M. Jaspers

    2010-01-01

    Background. Knowledge about past disease, treatment, and possible late effects has previously been shown to be low in survivors of childhood cancer and their relatives. This study investigated the information needs of childhood cancer survivors and their parents and explored possible determinants fo

  9. Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection

    Directory of Open Access Journals (Sweden)

    Hashishe Mervat M

    2010-06-01

    Full Text Available Abstract Background Breast cancer is one of the most common diseases affecting women. Inherited susceptibility genes, BRCA1 and BRCA2, are considered in breast, ovarian and other common cancers etiology. BRCA1 and BRCA2 genes have been identified that confer a high degree of breast cancer risk. Objective Our study was performed to identify germline mutations in some exons of BRCA1 and BRCA2 genes for the early detection of presymptomatic breast cancer in females. Methods This study was applied on Egyptian healthy females who first degree relatives to those, with or without a family history, infected with breast cancer. Sixty breast cancer patients, derived from 60 families, were selected for molecular genetic testing of BRCA1 and BRCA2 genes. The study also included 120 healthy first degree female relatives of the patients, either sisters and/or daughters, for early detection of presymptomatic breast cancer mutation carriers. Genomic DNA was extracted from peripheral blood lymphocytes of all the studied subjects. Universal primers were used to amplify four regions of the BRCA1 gene (exons 2,8,13 and 22 and one region (exon 9 of BRCA2 gene using specific PCR. The polymerase chain reaction was carried out. Single strand conformation polymorphism assay and heteroduplex analysis were used to screen for mutations in the studied exons. In addition, DNA sequencing of the normal and mutated exons were performed. Results Mutations in both BRCA1 and BRCA2 genes were detected in 86.7% of the families. Current study indicates that 60% of these families were attributable to BRCA1 mutations, while 26.7% of them were attributable to BRCA2 mutations. Results showed that four mutations were detected in the BRCA1 gene, while one mutation was detected in the BRCA2 gene. Asymptomatic relatives, 80(67% out of total 120, were mutation carriers. Conclusions BRCA1 and BRCA2 genes mutations are responsible for a significant proportion of breast cancer. BRCA mutations

  10. Family history and breast cancer hormone receptor status in a Spanish cohort.

    Directory of Open Access Journals (Sweden)

    Xuejuan Jiang

    Full Text Available BACKGROUND: Breast cancer is a heterogenous disease that impacts racial/ethnic groups differently. Differences in genetic composition, lifestyles, reproductive factors, or environmental exposures may contribute to the differential presentation of breast cancer among Hispanic women. MATERIALS AND METHODS: A population-based study was conducted in the city of Santiago de Compostela, Spain. A total of 645 women diagnosed with operable invasive breast cancer between 1992 and 2005 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics of the tumors were collected. Hormone receptor negative tumors were compared with hormone receptor postive tumors on their clinico-pathological characteristics as well as risk factor profiles. RESULTS: Among the 645 breast cancer patients, 78% were estrogen receptor-positive (ER+ or progesterone receptor-positive (PR+, and 22% were ER-&PR-. Women with a family history of breast cancer were more likely to have ER-&PR- tumors than women without a family history (Odds ratio, 1.43; 95% confidence interval, 0.91-2.26. This association was limited to cancers diagnosed before age 50 (Odds ratio, 2.79; 95% confidence interval, 1.34-5.81. CONCLUSIONS: An increased proportion of ER-&PR- breast cancer was observed among younger Spanish women with a family history of the disease.

  11. Worry Is Good for Breast Cancer Screening: A Study of Female Relatives from the Ontario Site of the Breast Cancer Family Registry

    OpenAIRE

    Li Rita Zhang; Chiarelli, Anna M; Gord Glendon; Lucia Mirea; Knight, Julia A.; Andrulis, Irene L.; Paul Ritvo

    2012-01-01

    Background. Few prospective studies have examined associations between breast cancer worry and screening behaviours in women with elevated breast cancer risks based on family history. Methods. This study included 901 high familial risk women, aged 23–71 years, from the Ontario site of the Breast Cancer Family Registry. Self-reported breast screening behaviours at year-one followup were compared between women at low (N = 305), medium (N = 433), and high (N = 163) levels of baseline breast canc...

  12. Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese women.

    Directory of Open Access Journals (Sweden)

    Lap Ah Tse

    Full Text Available The role of family history to the risk of breast cancer was analyzed by incorporating menopausal status in Hong Kong Chinese women, with a particular respect to the estrogen receptor-positive (ER+ type.Seven hundred and forty seven breast cancer incident cases and 781 hospital controls who had completed information on family cancer history in first-degree relatives (nature father, mother, and siblings were recruited. Odds ratio for breast cancer were calculated by unconditional multiple logistic regression, stratified by menopausal status (a surrogate of endogenous female sex hormone level and age and type of relative affected with the disease. Further subgroup analysis by tumor type according to ER status was investigated.Altogether 52 (6.96% breast cancer cases and 23 (2.95% controls was found that the patients' one or more first-degree relatives had a history of breast cancer, showing an adjusted odds ratio (OR of 2.41 (95%CI: 1.45-4.02. An excess risk of breast cancer was restricted to the ER+ tumor (OR = 2.43, 95% CI: 1.38-4.28, with a relatively higher risk associated with an affected mother (OR = 3.97, 95%CI: 1.46-10.79 than an affected sister (OR = 2.06, 95%CI: 1.07-3.97, while the relative risk was more prominent in the subgroup of pre-menopausal women. Compared with the breast cancer overall, the familial risks to the ER+ tumor increased progressively with the number of affected first-degree relatives.This study provides new insights on a relationship between family breast cancer history, menopausal status, and the ER+ breast cancer. A separate risk prediction model for ER+ tumor in Asian population is desired.

  13. Family consent, communication, and advance directives for cancer disclosure: a Japanese case and discussion.

    OpenAIRE

    Akabayashi, A.; Fetters, M. D.; Elwyn, T S

    1999-01-01

    The dilemma of whether and how to disclose a diagnosis of cancer or of any other terminal illness continues to be a subject of worldwide interest. We present the case of a 62-year-old Japanese woman afflicted with advanced gall bladder cancer who had previously expressed a preference not to be told a diagnosis of cancer. The treating physician revealed the diagnosis to the family first, and then told the patient: "You don't have any cancer yet, but if we don't treat you, it will progress to a...

  14. Recent discoveries concerning the involvement of transcription factors from the Grainyhead-like family in cancer.

    Science.gov (United States)

    Mlacki, Michal; Kikulska, Agnieszka; Krzywinska, Ewa; Pawlak, Magdalena; Wilanowski, Tomasz

    2015-11-01

    The Grainyhead-like (GRHL) family of transcription factors has three mammalian members, which are currently termed Grainyhead-like 1 (GRHL1), Grainyhead-like 2 (GRHL2), and Grainyhead-like 3 (GRHL3). These factors adopt a DNA-binding immunoglobulin fold homologous to the DNA-binding domain of key tumor suppressor p53. Their patterns of expression are tissue and developmentally specific. Earlier studies of the GRHL proteins focused on their functions in mammalian development. In recent years, these factors have been linked to many different types of cancer: squamous cell carcinoma of the skin, breast cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, clear cell renal cell carcinoma, neuroblastoma, prostate cancer, and cervical cancer. The roles of GRHL proteins in these various types of cancer are complex, and in some cases appear to be contradictory: they can serve to promote cancer development, or they may act as tumor suppressors, depending on the particular GRHL protein involved and on the cancer type. The reasons for obvious discrepancies in results from different studies remain unclear. At the molecular level, the GRHL transcription factors regulate the expression of genes whose products are involved in cellular proliferation, differentiation, adhesion, and polarity. We herein review the roles of GRHL proteins in cancer development, and we critically examine relevant molecular mechanisms, which were proposed by different authors. We also discuss the significance of recent discoveries implicating the involvement of GRHL transcription factors in cancer and highlight potential future applications of this knowledge in cancer treatment. PMID:26069269

  15. Double Heterozygosity of BRCA2 and STK11 in Familial Breast Cancer Detected by Exome Sequencing

    Directory of Open Access Journals (Sweden)

    Mojgan ATAEI-KACHOUEI

    2015-10-01

    Full Text Available Background: Germ-line mutations of BRCA1 and BRCA2 genes are responsible for approximately 25-30% of dominantly inherited familial breast cancers; still a big part of genetic component is unknown. The aim of this study was to investigate genetic causes of familial breast cancer in a pedigree with recessive pattern of inheritance.Methods: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer. Sanger sequencing was applied for validation and segregation analysis of mutations.Results: Here, we describe a family with three affected sisters of early-onset invasive ductal carcinoma due to heterozygous frame shift mutation rs80359352 in BRCA2 gene as the first report in Iranian patients in association with a novel missense SNP of STK11 (p.S422G. These mutations are inherited from their normal father.Conclusion: Despite apparent recessive pattern of inheritance a dominant gene (here BRCA2 can be involved in pathogenesis of hereditary breast cancer which can be explained by incomplete penetrance of BRCA2 mutations. Keywords: BRCA2, Familial breast cancer, rs80359352, STK11, Iran

  16. Identification and management of women with a family history of breast cancer

    Science.gov (United States)

    Heisey, Ruth; Carroll, June C.

    2016-01-01

    Abstract Objective To summarize the best evidence on strategies to identify and manage women with a family history of breast cancer. Sources of information A PubMed search was conducted using the search terms breast cancer, guidelines, risk, family history, management, and magnetic resonance imaging screening from 2000 to 2016. Most evidence is level II. Main message Taking a good family history is essential when assessing breast cancer risk in order to identify women suitable for referral to a genetic counselor for possible genetic testing. Offering risk-reducing surgery (bilateral prophylactic mastectomy, bilateral salpingo-oophorectomy) to women with BRCA genetic mutations can save lives. All women with a family history of breast cancer should be encouraged to stay active and limit alcohol intake to less than 1 drink per day; some will qualify for chemoprevention. Women with a 20% to 25% or greater lifetime risk of breast cancer should be offered enhanced screening with annual magnetic resonance imaging in addition to mammography. Conclusion Healthy living and chemoprevention (for suitable women) could reduce breast cancer incidence; enhanced screening could result in earlier detection. Referring women who carry BRCA mutations for risk-reducing surgery will save lives. PMID:27737975

  17. Identification of familial clustering for cancer through the family health strategy program in the municipality of Angra dos Reis, Rio de Janeiro, Brazil.

    Science.gov (United States)

    Vieira, Daniela Koeller Rodrigues; Attianezi, Margareth; Esposito, Ana Carolina; Barth, Anneliese; Sequeira, Cecília; Krause, Nathália; Oliveira, Vivian; Lucidi, Alexandre; Serao, Cassio; Llerena, Juan C

    2015-01-01

    Identification of families with history of cancer in the municipality of Angra dos Reis, Rio de Janeiro (Brazil), through the Brazilian Unified Primary Health Care System was explored based in the Community Health Agents (CHA) program. This study was divided into two phases: a descriptive one with a cross-sectional epidemiological data of families with history of cancer based on CHA-collected data from home visits in four primary health care units. The second phase consisted in identifying familial clustering of three or more individuals with cancer through construction of a three-generation pedigree and revisited by an itinerant group of medical geneticists. Genetic counseling was carried out with the intent of selecting potential families at risk for hereditary familial cancers. In the first phase of the study, 1,581 families were interviewed by the CHA at their homes. A positive history for cancer was present in 42.3 % of families, comprising 22.3 % with only one case per family, 11.2 % with two cases, and 8.6 % with three or more cases in the family. The informant reported that 15 % of the cases were from the father lineage, 12 % from the mother lineage, and 12.1 % within siblings. In the remaining 60.9 % families, cancer was present in both sides of the family. The types of cancer reported were uterus 8.7 % (n = 137), stomach 7.7 % (n = 122), breast 6.9 % (n = 109), throat 6.8 % (n = 99), prostate 5.4 % (n = 85), lung 5.6 % (n = 88), bowel 3.7 % (n = 59), and unspecified sites in 6.8 % (n = 108) of families. No statistical differences were noted between the data collected on each primary care unit. In the second phase of the study, 136 families (2.9 %) from the total of families interviewed in phase 1 were selected due to the presence of three or more individuals with cancer in the family. Among those, only 73 families attended genetic counseling. Comparison between the data obtained by the CHA and the medical

  18. Familial aggregation of lung cancer in a high incidence area in China

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Y.T.; Xu, Y.C.; Yang, R.D.; Huang, C.F.; Xu, C.W.; He, X.Z. [Anhui Medical University, Anhui (China). School of Public Health

    2005-04-11

    To investigate whether lung cancer clusters in families in a high incidence county of China, an analysis was conducted using data on domestic fuel history and tobacco use for family members of 740 deceased lung cancer probands and 740 controls (probands' spouses). Lung cancer prevalence was compared among first-degree relatives of probands and of controls, taking into account various factors using logistic regression and generalised estimating equations. First-degree relatives of probands, compared with those of controls, showed an excess risk of lung cancer (odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.68 - 2.53). Overall, female relatives of probands had a greater risk than did their male counterparts, and the risk was 2.90- fold for parents of probands as compared with parents of spouses. Female relatives of probands had 2.67-fold greater risk than female controls. Lung cancer risk was particularly marked among mothers (OR = 3.78, 95% CI: 2.03 - 7.12). Having two or more affected relatives was associated with a 2.69 - 5.40-fold risk increase. The risk elevation was also found for other cancers overall. Results confirm previous findings of a genetic predisposition to lung cancer, and also imply that lung cancer may share a genetic background with other cancers.

  19. Family history, body mass index and survival in Japanese patients with stomach cancer: a prospective study.

    Science.gov (United States)

    Minami, Yuko; Kawai, Masaaki; Fujiya, Tsuneaki; Suzuki, Masaki; Noguchi, Tetsuya; Yamanami, Hideaki; Kakugawa, Yoichiro; Nishino, Yoshikazu

    2015-01-15

    Family history and nutritional status may affect the long-term prognosis of stomach cancer, but evidence is insufficient and inconsistent. To clarify the prognostic factors of stomach cancer, we conducted a prospective study of 1,033 Japanese patients with histologically confirmed stomach cancer who were admitted to a single hospital between 1997 and 2005. Family history of stomach cancer and pretreatment body mass index (BMI) were assessed using a self-administered questionnaire. Clinical data were retrieved from a hospital-based cancer registry. All patients were completely followed up until December, 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated according to family history in parents and siblings and BMI category. During a median follow-up of 5.3 years, 403 all-cause and 279 stomach cancer deaths were documented. Although no association with family history was observed in the patients overall, analysis according to age group found an increased risk of all-cause death associated with a history in first degree relatives (HR = 1.61, 95% CI: 0.93-2.78, p = 0.09) and with a parental history (HR = 1.86, 95% CI: 1.06-3.26) among patients aged under 60 years at diagnosis. BMI was related to all-cause and stomach cancer death among patients aged 60 and over, showing a J-shaped pattern (HR of all-cause death = 2.28 for BMI stomach cancer, especially parental history, may affect mortality among younger stomach cancer patients, whereas nutritional status may be a prognostic factor in older patients.

  20. Risk prediction for breast, endometrial, and ovarian cancer in white women aged 50 y or older: derivation and validation from population-based cohort studies.

    Directory of Open Access Journals (Sweden)

    Ruth M Pfeiffer

    Full Text Available BACKGROUND: Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer. METHODS AND FINDINGS: Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health-AARP Diet and Health Study [NIH-AARP], we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI; the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96-1.04 for breast cancer and 1.08 (95% CI: 0.97-1.19 for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11-1.29. The areas under the receiver operating characteristic curves (AUCs; discriminatory power were 0.58 (95% CI: 0.57-0.59, 0.59 (95% CI: 0.56-0.63, and 0.68 (95% CI: 0.66-0.70 for the breast, ovarian, and endometrial models, respectively. CONCLUSIONS: These models predict absolute risks for breast, endometrial, and ovarian

  1. Factors influencing receptivity to future screening options for pancreatic cancer in those with and without pancreatic cancer family history

    Directory of Open Access Journals (Sweden)

    Breitkopf Carmen

    2012-06-01

    Full Text Available Abstract Background Pancreatic cancer (PC is considered the most lethal cancer and approximately 10% of PC is hereditary. The purpose of the study was to assess attitudes of at-risk family members with two or more relatives affected with pancreas cancer (PC toward PC risk and future screening options. Methods At-risk family members and primary care controls were surveyed regarding perceived PC risk, PC worry/concern, attitude toward cancer screening, screening test accuracy, and intentions regarding PC screening via blood testing or more invasive endoscopic ultrasound (EUS. Results PC family members reported greater perceived risk of PC than controls (54% vs. 6%, respectively, p 89% receptivity to the potential PC screening options presented, though receptivity was greater among PC family members as compared to controls (p  Conclusions Receptivity to screening options for PC appears high. Clinicians should address behavioral and genetic risk factors for PC and foster appropriate concern regarding PC risk among at-risk individuals.

  2. Long-term effects of first degree family history of breast cancer in young women: Recurrences and bilateral breast cancer

    NARCIS (Netherlands)

    Jobsen, Jan J.; Palen, van der Job; Brinkhuis, Mariël; Ong, Francisca; Struikmans, Henk

    2015-01-01

    Background. The aim of this study is to analyze the impact of first degree relative (FDR) of young breast cancer patients. Methods. Data were used from our prospective population-based cohort study which started in 1983. The family history (FH) was registered with regard to FDR: the presence or abs

  3. The results of gynecologic surveillance in families with hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Gerdes, Anne-Marie; Mosgaard, Berit;

    2014-01-01

    with gynecological malignancies or premalignancies were diagnosed. Thirty-nine women had EC. Of these, 31 were from families with identified MMR gene mutations with the median age at diagnosis of 54 (39-83) years (Incidence Rate, IR = 0.63 per 100 women years) and four women from each Amsterdam (AMS)-positive......Objective. We aimed to estimate the incidence rate of endometrial cancer (EC) and to evaluate the results of EC-surveillance in hereditary nonpolyposis colorectal cancer (HNPCC) families. Methods. All at-risk women recommended for EC-surveillance by the HNPCC-register-2959 women (19,334 women years...... and AMS-like families (median age 64 (55-73) years, IR = 0.06 and 0.05 per 100 women years, respectively, p cancers, diagnosed at the first visit-and 6/13 based on symptoms...

  4. An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Michał Kiciński

    Full Text Available Studies on familial aggregation of cancer may suggest an overall contribution of inherited genes or a shared environment in the development of malignant disease. We performed a meta-analysis on familial clustering of prostate cancer. Out of 74 studies reporting data on familial aggregation of prostate cancer in unselected populations retrieved by a Pubmed search and browsing references, 33 independent studies meeting the inclusion criteria were used in the analysis performed with the random effects model. The pooled rate ratio (RR for first-degree family history, i.e. affected father or brother, is 2.48 (95% confidence interval: 2.25-2.74. The incidence rate for men who have a brother who got prostate cancer increases 3.14 times (CI:2.37-4.15, and for those with affected father 2.35 times (CI:2.02-2.72. The pooled estimate of RR for two or more affected first-degree family members relative to no history in father and in brother is 4.39 (CI:2.61-7.39. First-degree family history appears to increase the incidence rate of prostate cancer more in men under 65 (RR:2.87, CI:2.21-3.74, than in men aged 65 and older (RR:1.92, CI:1.49-2.47, p for interaction = 0.002. The attributable fraction among those having an affected first-degree relative equals to 59.7% (CI:55.6-63.5% for men at all ages, 65.2% (CI:57.7-71.4% for men younger than 65 and 47.9% (CI:37.1-56.8% for men aged 65 or older. For those with a family history in 2 or more first-degree family members 77.2% (CI:65.4-85.0% of prostate cancer incidence can be attributed to the familial clustering. Our combined estimates show strong familial clustering and a significant effect-modification by age meaning that familial aggregation was associated with earlier disease onset (before age 65.

  5. The EGFR family of receptors sensitizes cancer cells towards UV light

    DEFF Research Database (Denmark)

    Petersen, Steffen B.; Neves Petersen, Teresa; Olsen, Birgitte

    2008-01-01

    A combination of bioinformatics, biophysical, advanced laser studies and cell biology lead to the realization that laser-pulsed UV light stops cancer growth and induces apoptosis. We have previously shown that laser-pulsed UV (LP-UV) illumination of two different skin-derived cancer cell lines both...... bridges. The EGF receptor is often overexpressed in cancers and other proliferative skin disorders, it might be possible to significantly reduce the proliferative potential of these cells making them good targets for laser-pulsed UV-light treatment. The discovery that UV light can be used to open...... that are sensitive to UV light lead to the prediction that UV light could modify these receptors permanently and stop cancer proliferation. We hereby show that the EGFR family of receptors has the necessary structural motifs that make this family of proteins highly sensitive to UV light....

  6. [Participation of the family in hospital-based palliative cancer care: perspective of nurses].

    Science.gov (United States)

    da Silva, Marcelle Miranda; Lima, Lorhanna da Silva

    2014-12-01

    The objective was to understand the perspective of nurses about the participation of the family in palliative cancer care and to analyze the nursing care strategies to meet their needs. Descriptive and qualitative research, conducted at the National Cancer Institute between January and March 2013, with 17 nurses. Elements of the Roy Adaptation Model were used for the interpretation of the data. Two categoriesemergedfrom the thematic analysis: perspective of nurses about the presence and valuation of family in the hospital; and appointing strategies to encourage family participation in care and meet their needs. This participation is essentialand represents a training opportunity for the purpose of homecare. Nurses create strategies to encourage it and seek to meet the needs. The results contribute to promote the family adaptation and integrity, in order to balance the dependent and independent behaviors, aimingfor quality of life and comfort. Further studies are neededdue to the challenges of the specialty. PMID:25842775

  7. Genome instability in blood cells of a BRCA1+ breast cancer family

    International Nuclear Information System (INIS)

    BRCA1 plays an essential role in maintaining genome stability. Inherited BRCA1 germline mutation (BRCA1+) is a determined genetic predisposition leading to high risk of breast cancer. While BRCA1+ induces breast cancer by causing genome instability, most of the knowledge is known about somatic genome instability in breast cancer cells but not germline genome instability. Using the exome-sequencing method, we analyzed the genomes of blood cells in a typical BRCA1+ breast cancer family with an exon 13-duplicated founder mutation, including six breast cancer-affected and two breast cancer unaffected members. We identified 23 deleterious mutations in the breast cancer-affected family members, which are absent in the unaffected members. Multiple mutations damaged functionally important and breast cancer-related genes, including transcriptional factor BPTF and FOXP1, ubiquitin ligase CUL4B, phosphorylase kinase PHKG2, and nuclear receptor activator SRA1. Analysis of the mutations between the mothers and daughters shows that most mutations were germline mutation inherited from the ancestor(s) while only a few were somatic mutation generated de novo. Our study indicates that BRCA1+ can cause genome instability with both germline and somatic mutations in non-breast cells

  8. Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases

    International Nuclear Information System (INIS)

    ERBB family receptor tyrosine kinases are overexpressed in a significant subset of breast cancers. One of these receptors, HER2/neu, or ErbB-2, is the target for a new rational therapeutic antibody, Herceptin. Other inhibitors that target this receptor, and another family member, the epidermal growth factor (EGF) receptor, are moving into clinical trials. Both of these receptors are sometimes overexpressed in breast cancer, and still subject to regulation by hormones and other physiological regulators. Optimal use of therapeutics targeting these receptors will require consideration of the several modes of regulation of these receptors and their interactions with steroid receptors

  9. Gatekeeper role of gastroenterologists and surgeons in recognising and discussing familial colorectal cancer.

    Science.gov (United States)

    Douma, Kirsten F L; Dekker, Evelien; Smets, Ellen M A; Aalfs, Cora M

    2016-04-01

    This study aimed to gain insight into the gatekeeper role of surgeons and gastroenterologists (including residents) during a first consultation at a tertiary gastro-intestinal centre regarding referral for genetic counselling, and to test the feasibility of a checklist for indications for referral. Consecutive patients were invited before and after introduction of a checklist, to complete a questionnaire assessing their perception of discussing cancer genetic topics. Initial consultations were audiotaped to assess the quality of this discussion by gastroenterologists and surgeons. Data on completeness of the checklist and referral were collected from medical files. No significant differences were found between the Before and After group regarding patients' reports of discussing cancer in the family (77%, n = 34 vs 89%, n = 33, p = 0.16). In 28% (n = 10) of the audiotaped consultations family history was adequately discussed, in 58% (n = 21) it was considered inadequate and in 14% (n = 5) of consultations it was not discussed at all. A checklist was present in 53% (n = 27) of the medical files. Of these, 5 (19%) were incomplete. Gastroenterologists and surgeons (in training) have difficulty in fulfilling their gatekeeper role of recognizing patients at familial risk for CRC. Although they often discuss familial cancer during the initial consultation, their exploration seems insufficient to reveal indications for referral for genetic counselling. Therefore, healthcare professionals should not only understand genetics and the importance of cancer family history, but also be effective in the communication of this subject to enable more adequate referral of patients for genetic counselling.

  10. Colorectal Cancer in the Family: Psychosocial Distress and Social Issues in the Years Following Genetic Counselling

    OpenAIRE

    Bleiker Eveline MA; Menko Fred H; Kluijt Irma; Taal Babs G; Gerritsma Miranda A; Wever Lidwina DV; Aaronson Neil K

    2007-01-01

    Abstract Background This study examined: (1) levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC); (2) associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3) the impact of genetic counselling on family relationships, and (4) social consequences of genetic counselling. Methods In this cross-sectional study, individuals who had received genetic counselling for HNPCC dur...

  11. Quality of life of adolescents with cancer: family risks and resources

    Directory of Open Access Journals (Sweden)

    Marmer Paige L

    2010-06-01

    Full Text Available Abstract Purpose The goal of this study was to evaluate the relative contribution of treatment intensity, family sociodemographic risk, and family resources to health-related quality of life (QOL of 102 adolescents in treatment for cancer. Methods Adolescents and parents completed self-report measures of teen QOL, family functioning, and parent-child bonding. Based on parent report of family sociodemographic variables, an additive risk index was computed. A pediatric oncologist rated treatment intensity. Results Simultaneous regression analyses demonstrated the significant contribution of roles in family functioning and quality of parent-child relationship to prediction of psychosocial QOL (parent and teen-reported as well as parent-reported teen physical QOL over and above the contribution of treatment intensity. Family sociodemographic risk did not contribute to QOL in these regression analyses. In additional analyses, specific diagnosis, types of treatment and individual sociodemographic risk variables were not associated with QOL. Parent and teen ratings of family functioning and quality of life were concordant. Conclusions Family functioning, including quality of parent-child relationship, are central and potentially modifiable resistance factors in teen QOL while under treatment for cancer. Even more important than relying on diagnosis or treatment, screening for roles and relationships early in treatment may be an important aspect of determining risk for poor QOL outcomes.

  12. CANCER CAN BE PREVENTED

    Directory of Open Access Journals (Sweden)

    Akula Annapurna

    2013-09-01

    Full Text Available Life style factors are contributing significantly in cancer prevention. With the intake of proper and balanced diet ,cancer prevention is possible. Many foods are associated either with incidence or prevention of cancer. Plant based foods like fresh fruits, vegetables and whole grains rich in fiber, b-carotene, vitamins and antioxidants can prevent cancer. Fiber rich foods increase bowel movement, decreasing the absorption of cholesterol. Pumpkin, carrots contain b-carotenes. Leafy vegetables, broccoli, cabbage, cauliflower, peas and beans are rich in fiber and stimulate cancer preventing enzyme induction. Vitamin C rich citrus fruits can stimulate immune system. Garlic and onions can stimulate enzymes that can suppress tumor growth. Turmeric used in cooking can prevent colorectal cancer. Topical application of turmeric can prevent breast cancer in women. On the other hand, certain foods can cause cancer. Refined foods, high fat foods, deep fried foods, processed foods and low fiber foods increase cancer risk. Red meat, processed meat and barbeques contain a carcinogen called acrylamide. Foods prepared with hydrogenated fats contain transfats which increase risk for breast, ovarian, cervical and lung cancer. Consumption of alcohol increasing the risk for cancers of digestive system. LET US EAT RIGHT FOODS AND AVOID WRONG FOODS.

  13. Experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer

    OpenAIRE

    Gláucia Sousa Oliveira; Marina Bavaresco; Cibelle Barcelos Fillipini; Sara Rodrigues Rosado; Eliza Maria Rezende Dázio; Silvana Maria Coelho Leite Fava

    2014-01-01

    This is a study with the objective to know the experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer. A qualitative research, grounded on the humanization referential, made in 2013, through serialized semi-structured interviews and inductive analysis. It was approved by the Ethics and Research Committee under legal opinion no. 237,771. Seven family caregivers participated in this study in a county of southern Minas Gerais state, Brazil. Three categori...

  14. Lung cancer susceptibility model based on age, family history and genetic variants.

    Directory of Open Access Journals (Sweden)

    Robert P Young

    Full Text Available BACKGROUND: Epidemiological and pedigree studies suggest that lung cancer results from the combined effects of age, smoking, impaired lung function and genetic factors. In a case control association study of healthy smokers and lung cancer cases, we identified genetic markers associated with either susceptibility or protection to lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: We screened 157 candidate single nucleotide polymorphisms (SNP in a discovery cohort of 439 subjects (200 controls and 239 lung cancer cases and identified 30 SNPs associated with either the healthy smokers (protective or lung cancer (susceptibility phenotype. After genotyping this 30 SNP panel in a validation cohort of 491 subjects (248 controls and 207 lung cancers and, using the same protective and susceptibility genotypes from our discovery cohort, a 20 SNP panel was selected based on replication of SNP associations in the validation cohort. Following multivariate logistic regression analyses, including the selected SNPs from runs 1 and 2, we found age and family history of lung cancer to be significantly and independently associated with lung cancer. Numeric scores were assigned to both the SNP and demographic data, and combined to form a simple algorithm of risk. CONCLUSIONS/SIGNIFICANCE: Significant differences in the distribution of the lung cancer susceptibility score was found between normal controls and lung cancer cases, which remained after accounting for differences in lung function. Validation in other case-control and prospective cohorts are underway to further define the potential clinical utility of this model.

  15. Communicating with Terminally Ill Cancer Patients and Their Families.

    Science.gov (United States)

    Hjorleifsdottir, Elisabet; Carter, Diana E.

    2000-01-01

    Interviews with 12 fourth-year student nurses in Scotland indicated that they found communicating with terminally ill and dying patients and their families difficult. Although lectures on death and dying were helpful, support and guidance for dealing with these issues in clinical practice were needed. (SK)

  16. The rationale for targeting the LOX family in cancer

    DEFF Research Database (Denmark)

    Barker, Holly E; Cox, Thomas R; Erler, Janine T

    2012-01-01

    The therapeutic targeting of extracellular proteins is becoming hugely attractive in light of evidence implicating the tumour microenvironment as pivotal in all aspects of tumour initiation and progression. Members of the lysyl oxidase (LOX) family of proteins are secreted by tumours and are the...

  17. An effect from anticipation also in hereditary nonpolyposis colorectal cancer families without identified mutations

    DEFF Research Database (Denmark)

    Timshel, Susanne; Therkildsen, Christina; Bendahl, Pär-Ola;

    2009-01-01

    Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC...... the Amsterdam criteria for HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene mutation. In total, 319 cancers from 212 parent-child pairs in 99 families were identified. A paired t-test and a bivariate statistical model were used to assess anticipation. Both methods demonstrated...

  18. H. pylori-associated gastric cancer in a husband-wife pair: a veritable family affair.

    Science.gov (United States)

    Dasanu, Constantin A; Rathmann, Joerg; Alexandrescu, Doru T

    2009-11-01

    Family environment probably represents a high route of transmission for H. pylori, a bacterium associated with gastric cancer (GC). We report two cases of GC in a husband-wife pair of immigrants from Romania. The disease was first diagnosed in the wife, and three years later in her husband of 55 years. Both patients had active H. pylori-related inflammation. Household family members of GC patients could be infected with a shared H. pylori strain, putting them at risk for developing the disease. Therefore, it may be justified to identify and eradicate the H. pylori infection in such family members early, before the neoplastic changes become irreversible.

  19. Approach to early-onset colorectal cancer:Clinicopathological,familial,molecular and immunohistochemical characteristics

    Institute of Scientific and Technical Information of China (English)

    Jose; Perea; Edurne; Alvaro; Yolanda; Rodríguez; Cristina; Gravalos; Eva; Sánchez-Tomé; Barbara; Rivera; Francisco; Colina; Pablo; Carbonell; Rogelio; González-Sarmiento; Manuel; Hidalgo; Miguel; Urioste

    2010-01-01

    AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC aged 45 or younger were included in the study.Clinical information,a three-generation family history,and tumor samples were obtained.MSI status was analyzed and mismatch repair genes were examined in the MSI families.Tumors were included in a tissue microarray and an immunohistochemical study w...

  20. No evidence of increased breast cancer risk for proven noncarriers from BRCA1 and BRCA2 families

    DEFF Research Database (Denmark)

    Nielsen, Henriette Roed; Petersen, Janne; Krogh, Lotte;

    2016-01-01

    In families screened for mutations in the BRCA1 or BRCA2 genes and found to have a segregating mutation the breast cancer risk for women shown not to carry the family-specific mutation might be at above "average" risk. We assessed the risk of breast cancer in a clinic based cohort of 725 female...

  1. Familial prostate cancer: outcome following radiation therapy with or without adjuvant androgen ablation

    International Nuclear Information System (INIS)

    Purpose: To compare the outcome of familial versus sporadic prostate carcinoma after definitive external radiation. Methods and Materials: Between 1987 and 1996, 1214 men with clinically localized prostate cancer (T1-T4, N0/NX, M0) received definitive radiation therapy in our department. By retrospective review of charts and questioning of patients, a record on the presence or absence of prostate cancer in a first degree relative was obtained in 1164 men. Univariate and multivariate analysis was performed on these cases with relapse or rising prostate-specific antigen (PSA), local recurrence, metastasis, and survival as endpoints. Results: Familiar prostate cancer was present in 148 of 1164 men (13%). Men with familial disease were slightly but significantly younger (mean 66 years) at diagnosis than those with sporadic disease (mean 68 years) (p = 0.02). Apart from this there were no significant differences between the two groups in T-stage, Gleason score, pretreatment PSA levels, DNA ploidy, or serum testosterone levels. There were no significant differences in treatment parameters including radiation dose and the use of adjuvant androgen ablation. With a median follow-up of 42 months, there was no difference in freedom from relapse or rising PSA at 6 years between those with a family history (54%) and those without a family history (58%) (p = 0.171). Likewise there was no difference between the two groups when local recurrence or metastasis was the endpoint. Multiple subgroup analyses (younger and older; T1/T2 and T3; low Gleason and high Gleason; no androgen ablation and androgen ablation; race) failed to reveal any differences in outcome in any category between familial and sporadic disease. Among patients with a rising post-treatment PSA profile, PSA doubling times were similar in those with sporadic and familial disease. Conclusions: This study provides no evidence for any substantial difference between familial and sporadic prostate cancer either in

  2. Expression of OATP family members in hormone-related cancers: potential markers of progression.

    Directory of Open Access Journals (Sweden)

    Heather Pressler

    Full Text Available The organic anion transporting polypeptide (OATP family of transporters has been implicated in prostate cancer disease progression probably by transporting hormones or drugs. In this study, we aimed to elucidate the expression, frequency, and relevance of OATPs as a biomarker in hormone-dependent cancers. We completed a study examining SLCO1B3, SLCO1B1 and SLCO2B1 mRNA expression in 381 primary, independent patient samples representing 21 cancers and normal tissues. From a separate cohort, protein expression of OATP1B3 was examined in prostate, colon, and bladder tissue. Based on expression frequency, SLCO2B1 was lower in liver cancer (P = 0.04 which also trended lower with decreasing differentiation (P = 0.004 and lower magnitude in pancreatic cancer (P = 0.05. SLCO2B1 also had a higher frequency in thyroid cancer (67% than normal (0% and expression increased with stage (P = 0.04. SLCO1B3 was expressed in 52% of cancerous prostate samples and increased SLCO1B3 expression trended with higher Gleason score (P = 0.03. SLCO1B3 expression was also higher in testicular cancer (P = 0.02. SLCO1B1 expression was lower in liver cancer (P = 0.04 which trended lower with liver cancer grade (P = 0.0004 and higher with colon cancer grade (P = 0.05. Protein expression of OATP1B3 was examined in normal and cancerous prostate, colon, and bladder tissue samples from an independent cohort. The results were similar to the transcription data, but showed distinct localization. OATPs correlate to differentiation in certain hormone-dependent cancers, thus may be useful as biomarkers for assessing clinical treatment and stage of disease.

  3. Identification of familial clustering for cancer through the family health strategy program in the municipality of Angra dos Reis, Rio de Janeiro, Brazil

    OpenAIRE

    Vieira, Daniela Koeller Rodrigues; Attianezi, Margareth; Esposito, Ana Carolina; Barth, Anneliese; Sequeira, Cecília; Krause, Nathália; Oliveira, Vivian; Lucidi, Alexandre; Serao, Cassio; Llerena, Juan C

    2014-01-01

    Identification of families with history of cancer in the municipality of Angra dos Reis, Rio de Janeiro (Brazil), through the Brazilian Unified Primary Health Care System was explored based in the Community Health Agents (CHA) program. This study was divided into two phases: a descriptive one with a cross-sectional epidemiological data of families with history of cancer based on CHA-collected data from home visits in four primary health care units. The second phase consisted in identifying fa...

  4. Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

    Science.gov (United States)

    Ashkani, Jahanshah; Naidoo, Kevin J.

    2016-05-01

    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

  5. Accuracy of Self-Reported Breast Cancer Information among Women from the Ontario Site of the Breast Cancer Family Registry

    Directory of Open Access Journals (Sweden)

    Andriana Barisic

    2012-01-01

    Full Text Available Obtaining complete medical record information can be challenging and expensive in breast cancer studies. The current literature is limited with respect to the accuracy of self-report and factors that may influence this. We assessed the agreement between self-reported and medical record breast cancer information among women from the Ontario site of the Breast Cancer Family Registry. Women aged 20–69 years diagnosed with incident breast cancer 1996–1998 were identified from the Ontario Cancer Registry, sampled on age and family history. We calculated kappa statistics, proportion correct, sensitivity, specificity, and positive and negative predictive values and conducted unconditional logistic regression to examine whether characteristics of the women influenced agreement. The proportions of women who correctly reported having received a broad category of therapy (hormone therapy, chemotherapy, radiation, or surgery as well as sensitivity and specificity were above 90%, and the kappa statistics were above 0.80. The specific type of hormonal or chemotherapy was reported with low-to-moderate agreement. Aside from recurrence, no factors were consistently associated with agreement. Thus, most women were able to accurately report broad categories of treatment but not necessarily specific treatment types. The finding of this study can aid researchers in the use and design of self-administered treatment questionnaires.

  6. Factors Associated with Colorectal Cancer Risk Perception: The Role of Polyps and Family History

    Science.gov (United States)

    Stark, Jennifer Rider; Bertone-Johnson, Elizabeth R.; Costanza, Mary E.; Stoddard, Anne M.

    2006-01-01

    It is unclear how objective risk factors influence the factors associated with colorectal cancer (CRC) risk perception. The goals of this study were to investigate factors associated with perceived risk of CRC and to explore how these relationships were modified by personal history of polyps or family history of CRC. The study involved a mailed…

  7. Risk of Breast Cancer in Families with Cleft Lip and Palate

    DEFF Research Database (Denmark)

    Dietz, Alexander; Pedersen, Dorthe Almind; Jacobsen, Rune;

    2012-01-01

    PURPOSE: To test whether female subjects in families with cleft lip and/or palate (CL/P) have an increased risk of breast cancer. METHODS: By using the Danish Facial Cleft Registry, we identified female subjects with CL/P, mothers of children with CL/P, and sisters to CL/P cases for the Danish...

  8. Coping and family functioning predict longitudinal psychological adaptation of siblings of childhood cancer patients

    NARCIS (Netherlands)

    Houtzager, BA; Oort, FJ; Hoekstra-Weebers, JEHM; Caron, HN; Grootenhuis, MA; Last, BF

    2004-01-01

    Objective To assess associations of coping and family functioning with psychosocial adjustment in siblings of pediatric cancer patients at 1, 6, 12, and 24 months after diagnosis. Methods Eighty-three siblings (ages 7-19 years) participated. Effects on anxiety, quality of life, behavioral-emotional

  9. The impact of stratifying by family history in colorectal cancer screening programs

    NARCIS (Netherlands)

    S.L. Goede (S. Lucas); L. Rabeneck (L.); I. Lansdorp-Vogelaar (Iris); A. Zauber (Ann); L.F. Paszat (Lawrence F.); J.S. Hoch (Jeffrey S.); J.H.E. Yong (Jean H.E.); F. Van Hees (Frank); J. Tinmouth (Jill); M. van Ballegooijen (Marjolein)

    2015-01-01

    textabstractIn the province-wide colorectal cancer (CRC) screening program in Ontario, Canada, individuals with a family history of CRC are offered colonoscopy screening and those without are offered guaiac fecal occult blood testing (gFOBT, Hemoccult II). We used microsimulation modeling to estimat

  10. Recommendations to improve identification of hereditary and familial colorectal cancer in Europe

    NARCIS (Netherlands)

    Vasen, H. F. A.; Moeslein, G.; Alonso, A.; Aretz, S.; Bernstein, I.; Bertario, L.; Blanco, I.; Bulow, S.; Burn, J.; Capella, G.; Colas, C.; Engel, C.; Frayling, I.; Rahner, N.; Hes, F. J.; Hodgson, S.; Mecklin, J. -P.; Moller, P.; Myrhoj, T.; Nagengast, F. M.; Parc, Y.; de Leon, M. Ponz; Renkonen-Sinisalo, L.; Sampson, J. R.; Stormorken, A.; Tejpar, S.; Thomas, H. J. W.; Wijnen, J.; Lubinski, J.; Jarvinen, H.; Claes, E.; Heinimann, K.; Karagiannis, J. A.; Lindblom, A.; Dove-Edwin, I.; Mueller, H.

    2010-01-01

    Familial colorectal cancer (CRC) accounts for 10-15% of all CRCs. In about 5% of all cases, CRC is associated with a highly penetrant dominant inherited syndrome. The most common inherited form of non-polyposis CRC is the Lynch syndrome which is responsible for about 2-4% of all cases. Surveillance

  11. Interaction of Dietary Fatty Acids with Tumour Necrosis Factor Family Cytokines during Colon Inflammation and Cancer

    Directory of Open Access Journals (Sweden)

    Jiřina Hofmanová

    2014-01-01

    Full Text Available Intestinal homeostasis is precisely regulated by a number of endogenous regulatory molecules but significantly influenced by dietary compounds. Malfunction of this system may result in chronic inflammation and cancer. Dietary essential n-3 polyunsaturated fatty acids (PUFAs and short-chain fatty acid butyrate produced from fibre display anti-inflammatory and anticancer activities. Both compounds were shown to modulate the production and activities of TNF family cytokines. Cytokines from the TNF family (TNF-α, TRAIL, and FasL have potent inflammatory activities and can also regulate apoptosis, which plays an important role in cancer development. The results of our own research showed enhancement of apoptosis in colon cancer cells by a combination of either docosahexaenoic acid (DHA or butyrate with TNF family cytokines, especially by promotion of the mitochondrial apoptotic pathway and modulation of NFκB activity. This review is focused mainly on the interaction of dietary PUFAs and butyrate with these cytokines during colon inflammation and cancer development. We summarised recent knowledge about the cellular and molecular mechanisms involved in such effects and outcomes for intestinal cell behaviour and pathologies. Finally, the possible application for the prevention and therapy of colon inflammation and cancer is also outlined.

  12. A risk management model for familial breast cancer: A new application using Fuzzy Cognitive Map method.

    Science.gov (United States)

    Papageorgiou, Elpiniki I; Jayashree Subramanian; Karmegam, Akila; Papandrianos, Nikolaos

    2015-11-01

    Breast cancer is the most deadly disease affecting women and thus it is natural for women aged 40-49 years (who have a family history of breast cancer or other related cancers) to assess their personal risk for developing familial breast cancer (FBC). Besides, as each individual woman possesses different levels of risk of developing breast cancer depending on their family history, genetic predispositions and personal medical history, individualized care setting mechanism needs to be identified so that appropriate risk assessment, counseling, screening, and prevention options can be determined by the health care professionals. The presented work aims at developing a soft computing based medical decision support system using Fuzzy Cognitive Map (FCM) that assists health care professionals in deciding the individualized care setting mechanisms based on the FBC risk level of the given women. The FCM based FBC risk management system uses NHL to learn causal weights from 40 patient records and achieves a 95% diagnostic accuracy. The results obtained from the proposed model are in concurrence with the comprehensive risk evaluation tool based on Tyrer-Cuzick model for 38/40 patient cases (95%). Besides, the proposed model identifies high risk women by calculating higher accuracy of prediction than the standard Gail and NSAPB models. The testing accuracy of the proposed model using 10-fold cross validation technique outperforms other standard machine learning based inference engines as well as previous FCM-based risk prediction methods for BC. PMID:26220142

  13. A BAP1 mutation in a Danish family predisposes to uveal melanoma and other cancers.

    Directory of Open Access Journals (Sweden)

    Lauren G Aoude

    Full Text Available Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (BAP1 have been reported in families predisposed to developing a wide range of different cancer types including uveal melanoma and cutaneous melanoma. There has also been an association between amelanotic tumor development and germline BAP1 mutation suggesting a possible phenotypic characteristic of BAP1 mutation carriers. Though there have been many types of cancer associated with germline BAP1 mutation, the full spectrum of disease association is yet to be ascertained. Here we describe a Danish family with predominantly uveal melanoma but also a range of other tumor types including lung, neuroendocrine, stomach, and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing identified a BAP1 splice mutation located at c.581-2A>G, which leads to a premature truncation of BAP1 in an individual with uveal melanoma. This mutation was carried by several other family members with melanoma or various cancers. The finding expands on the growing profile of BAP1 as an important uveal and cutaneous melanoma tumor suppressor gene and implicates its involvement in the development of lung, and stomach cancer.

  14. Colorectal Cancer in the Family: Psychosocial Distress and Social Issues in the Years Following Genetic Counselling

    Directory of Open Access Journals (Sweden)

    Bleiker Eveline MA

    2007-06-01

    Full Text Available Abstract Background This study examined: (1 levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC; (2 associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3 the impact of genetic counselling on family relationships, and (4 social consequences of genetic counselling. Methods In this cross-sectional study, individuals who had received genetic counselling for HNPCC during 1986–1998 completed a self-report questionnaire by mail. Results 116 individuals (81% response rate completed the questionnaire, on average 4 years after the last counselling session. Of all respondents, 6% had clinically significant levels of cancer-specific distress (Impact of Event Scale, IES. Having had contact with a professional psychosocial worker for cancer risk in the past 10 years was significantly associated with higher levels of current cancer specific distress. Only a minority of the counselees reported any adverse effects of genetic counselling on: communication about genetic counselling with their children (9%, family relationships (5%, obtaining life insurance (8%, choice or change of jobs (2%, and obtaining a mortgage (2%. Conclusion On average, four years after genetic counselling for HNPCC, only a small minority of counselled individuals reports clinically significant levels of distress, or significant family or social problems.

  15. The Attitudes of Chinese Cancer Patients and Family Caregivers toward Advance Directives

    Directory of Open Access Journals (Sweden)

    Qiu Zhang

    2016-08-01

    Full Text Available Advance directives (ADs have been legislated in many countries to protect patient autonomy regarding medical decisions at the end of life. China is facing a serious cancer burden and cancer patients’ quality at the end of life should be a concern. However, limited studies have been conducted locally to gather information about attitudes toward ADs. The purpose of this study was to investigate the attitudes of Chinese cancer patients and family caregivers toward ADs and to explore the predictors that are associated with attitudes. The study indicated that although there was low awareness of ADs, most cancer patients and family caregivers had positive attitudes toward ADs after related information was explained to them. Participants preferred to discuss ADs with medical staff when they were diagnosed with a life-threatening disease. Preferences for refusing life-sustaining treatment and choosing Hospice-Palliative Care (HPC at the end of life would increase the likelihood of agreeing with ADs. This suggests that some effective interventions to help participants better understand end-of-life treatments are helpful in promoting ADs. Moreover, the development of HPC would contribute to Chinese cancer patients and family caregivers agreeing with ADs.

  16. Does family history of cancer modify the effects of lifestyle risk factors on esophageal cancer? A population-based case-control study in China

    NARCIS (Netherlands)

    Wu, M.; Zhang, Z.F.; Kampman, E.; Zhou, J.Y.; Han, R.Q.; Yang, J.; Zhang, X.F.; Gu, X.P.; Liu, A.M.; Veer, P. van 't; Kok, F.J.; Zhao, J.K.

    2011-01-01

    A population-based case-control study on esophageal cancer has been conducted since 2003 in Jiangsu Province, China. The aim of this analysis is to provide further evidence on the relationship between family history of cancer in first-degree relatives (FH-FDRs) and the risk of esophageal cancer, and

  17. A BAP1 Mutation in a Danish Family Predisposes to Uveal Melanoma and Other Cancers

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin; Bojesen, Anders;

    2013-01-01

    Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (BAP1) have been reported in families predisposed to developing a wide range of different cancer types including uveal melanoma and cutaneous melanoma. There has also been an association between amelanotic tumor...... development and germline BAP1 mutation suggesting a possible phenotypic characteristic of BAP1 mutation carriers. Though there have been many types of cancer associated with germline BAP1 mutation, the full spectrum of disease association is yet to be ascertained. Here we describe a Danish family...... with predominantly uveal melanoma but also a range of other tumor types including lung, neuroendocrine, stomach, and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing identified a BAP1 splice mutation located at c.581-2A>G, which leads to a premature truncation of BAP1 in an individual...

  18. Association of in vitro radiosensitivity and cancer in a family with acute myelogenous leukemia

    International Nuclear Information System (INIS)

    The γ-ray sensitivity of skin fibroblasts from six members of a cancer family was investigated using a colony-forming assay. Fibroblasts from the three members with cancer (two sisters with acute myelogenous leukemia and the mother with cervical carcinoma) showed a significant ( p > 0.05) increase in radiosensitivity, while three members without cancer (the father and two sons) showed a normal radioresponse. The possiblity that the increased γ-ray sensitivity was due to defective DNA repair was investigated using assays for DNA repair replication, single-strand break rejoining, and removal of enzyme-sensitive sites in γ-irradiated DNA. Results of these assays indicate that the kinetics of enzymatic repair of radiogenic DNA damage in general, and the rejoining of single-strand scissions and excision repair of base and sugar radioproducts in partigular, were the same in the cell lines from the sensitive and clinically normal family members

  19. MicroRNA-200 Family Profile: A Promising Ancillary Tool for Accurate Cancer Diagnosis.

    Science.gov (United States)

    Liu, Xiaodong; Zhang, Jianhua; Xie, Botao; Li, Hao; Shen, Jihong; Chen, Jianheng

    2016-01-01

    Cancer is one of the most threatening diseases in the world and great interests have been paid to discover accurate and noninvasive methods for cancer diagnosis. The value of microRNA-200 (miRNA-200, miR-200) family has been revealed in many studies. However, the results from various studies were inconsistent, and thus a meta-analysis was designed and performed to assess the overall value of miRNA200 in cancer diagnosis. Relevant studies were searched electronically from the following databases: PubMed, Embase, Web of Science, the Cochrane Library, and Chinese National Knowledge Infrastructure. Keyword combined with "miR-200," "cancer," and "diagnosis" in any fields was used for searching relevant studies. Then, the pooled sensitivity, specificity, area under the curve (AUC), and partial AUC were calculated using the random-effects model. Heterogeneity among individual studies was also explored by subgroup analyses. A total of 28 studies from 18 articles with an overall sample size of 3676 subjects (2097 patients and 1579 controls) were included in this meta-analysis. The overall sensitivity and specificity with 95% confidence intervals (95% CIs) are 0.709 (95% CI: 0.657-0.755) and 0.667 (95% CI: 0.617-0.713), respectively. Additionally, AUC and partial AUC for the pooled data is 0.735 and 0.627, respectively. Subgroup analyses revealed that using miRNA-200 family for cancer diagnosis is more effective in white than in Asian ethnic groups. In addition, cancer diagnosis by miRNA using circulating specimen is more effective than that using noncirculating specimen. Finally, miRNA is more accurate in diagnosing endometrial cancer than other types of cancer, and some miRNA family members (miR-200b and miR-429) have superior diagnostic accuracy than other miR-200 family members. In conclusion, the profiling of miRNA-200 family is likely to be a valuable tool in cancer detection and diagnosis.

  20. IGFBP1 and IGFBP3 polymorphisms predict circulating IGFBP-3 levels among women from high-risk breast cancer families

    OpenAIRE

    Rosendahl, Ann; Hietala, Maria; Henningson, Maria; Olsson, Håkan; Jernström, Helena

    2010-01-01

    Abstract The insulin-like growth factor (IGF) pathway has been implicated as risk modifier in premenopausal breast cancer. In this study, associations between single nucleotide polymorphisms (SNPs) and diplotypes in the IGFBP1 and IGFBP3 genes and circulating IGFBP-3 levels, BRCA family status and breast cancer among women from high-risk breast cancer families were investigated. Nine IGFBP1 and IGFBP3 SNPs were genotyped with PCR-based methods in 323 women. Nine IGFBP1 and ten IGFB...

  1. Germline mutations in MAP3K6 are associated with familial gastric cancer.

    Directory of Open Access Journals (Sweden)

    Daniel Gaston

    2014-10-01

    Full Text Available Gastric cancer is among the leading causes of cancer-related deaths worldwide. While heritable forms of gastric cancer are relatively rare, identifying the genes responsible for such cases can inform diagnosis and treatment for both hereditary and sporadic cases of gastric cancer. Mutations in the E-cadherin gene, CDH1, account for 40% of the most common form of familial gastric cancer (FGC, hereditary diffuse gastric cancer (HDGC. The genes responsible for the remaining forms of FGC are currently unknown. Here we examined a large family from Maritime Canada with FGC without CDH1 mutations, and identified a germline coding variant (p.P946L in mitogen-activated protein kinase kinase kinase 6 (MAP3K6. Based on conservation, predicted pathogenicity and a known role of the gene in cancer predisposition, MAP3K6 was considered a strong candidate and was investigated further. Screening of an additional 115 unrelated individuals with non-CDH1 FGC identified the p.P946L MAP3K6 variant, as well as four additional coding variants in MAP3K6 (p.F849Sfs*142, p.P958T, p.D200Y and p.V207G. A somatic second-hit variant (p.H506Y was present in DNA obtained from one of the tumor specimens, and evidence of DNA hypermethylation within the MAP3K6 gene was observed in DNA from the tumor of another affected individual. These findings, together with previous evidence from mouse models that MAP3K6 acts as a tumor suppressor, and studies showing the presence of somatic mutations in MAP3K6 in non-hereditary gastric cancers and gastric cancer cell lines, point towards MAP3K6 variants as a predisposing factor for FGC.

  2. Supporting families with Cancer: A patient centred survivorship model of care.

    Science.gov (United States)

    Craft, Emily Victoria; Billington, Caron; O'Sullivan, Rory; Watson, Wendy; Suter-Giorgini, Nicola; Singletary, Joanne; King, Elizabeth; Perfirgines, Matthew; Cashmore, Annette; Barwell, Julian

    2015-12-01

    In 2011, the Leicestershire Clinical Genetics Department in collaboration with Macmillan Cancer Support initiated a project called Supporting Families with Cancer (SFWC). The project aimed to raise awareness of inherited cancers amongst both healthcare professionals and the general public and develop a patient-centred collaborative approach to cancer treatment and support services. This paper describes the project's development of a range of community outreach events and a training scheme for primary healthcare professionals designed to improve familial cancer referral rates in Leicester. Following consultation with patients and support groups, a series of interactive 'medical supermarket' events were held in Leicester. These events focused on providing patients with a forum for sharing research data, information about diagnosis and treatments and access to support groups and other allied healthcare services with additional information being made available digitally via SFWC webpages and a series of short videos available on a YouTube channel. Qualitative and quantitative data presented here indicate that the SFWC medical supermarket model has been well received by patients and offers a patient-centred, holistic approach to cancer treatment. PMID:26077135

  3. The ADAMs family of proteases: new biomarkers and therapeutic targets for cancer?

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2011-06-09

    Abstract The ADAMs are transmembrane proteins implicated in proteolysis and cell adhesion. Forty gene members of the family have been identified, of which 21 are believed to be functional in humans. As proteases, their main substrates are the ectodomains of other transmembrane proteins. These substrates include precursor forms of growth factors, cytokines, growth factor receptors, cytokine receptors and several different types of adhesion molecules. Although altered expression of specific ADAMs has been implicated in different diseases, their best-documented role is in cancer formation and progression. ADAMs shown to play a role in cancer include ADAM9, ADAM10, ADAM12, ADAM15 and ADAM17. Two of the ADAMs, i.e., ADAM10 and 17 appear to promote cancer progression by releasing HER\\/EGFR ligands. The released ligands activate HER\\/EGFR signalling that culminates in increased cell proliferation, migration and survival. Consistent with a causative role in cancer, several ADAMs are emerging as potential cancer biomarkers for aiding cancer diagnosis and predicting patient outcome. Furthermore, a number of selective ADAM inhibitors, especially against ADAM10 and ADAM17, have been shown to have anti-cancer effects. At least one of these inhibitors is now undergoing clinical trials in patients with breast cancer.

  4. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes

    DEFF Research Database (Denmark)

    Wandall, Hans H; Blixt, Ola; Tarp, Mads A;

    2010-01-01

    -glycopeptide microarray was developed that detected IgG antibodies to aberrant O-glycopeptide epitopes in patients vaccinated with a keyhole limpet hemocyanin-conjugated truncated MUC1 peptide. We detected cancer-associated IgG autoantibodies in sera from breast, ovarian, and prostate cancer patients against different...... evaluated whether autoantibodies generated to aberrant O-glycoforms of MUC1 might serve as sensitive diagnostic biomarkers for cancer. Using an antibody-based glycoprofiling ELISA assay, we documented that aberrant truncated glycoforms were not detected in sera of cancer patients. An O......Autoantibodies to cancer antigens hold promise as biomarkers for early detection of cancer. Proteins that are aberrantly processed in cancer cells are likely to present autoantibody targets. The extracellular mucin MUC1 is overexpressed and aberrantly glycosylated in many cancers; thus, we...

  5. A hypothesis-generating search for new genetic breast cancer syndromes - a national study in 803 Swedish families

    Directory of Open Access Journals (Sweden)

    von Wachenfeldt Anna

    2007-03-01

    Full Text Available Abstract Among Swedish families with an inherited predisposition for breast cancer, less than one third segregate mutations in genes known to be associated with an increased risk of breast cancer in combination with other types of tumours. In a search for new putative familial breast cancer syndromes we studied Swedish families undergoing genetic counselling during 1992-2000. Four thousand families from counselling clinics in Sweden were eligible for study. Families with breast cancer only were excluded, as were families with mutations in genes already known to be associated with malignant diseases. We identified 803 families with two or more cases of breast cancer and at least one other type of cancer. The observed proportion of different types of non-breast cancer was compared with the percentage distribution of non-breast cancer tumours in Sweden in 1958 and 1999. We found tumours in the colon, ovary, endometrium, pancreas and liver, as well as leukaemia in a significantly larger proportion of the study population than in the general population in both years. These tumours were also seen among families where several members had one additional tumour, suggesting that malignancies at these sites, in combination with breast tumours, could constitute genetic syndromes. Endometrial carcinoma has not previously been described in the context of breast cancer syndromes and the excess of malignancies at this site could not be explained by secondary tumours. Thus, we suggest that endometrial carcinoma and breast cancer constitute a new breast cancer syndrome. Further investigation is warranted to categorize phenotypes of both breast and endometrial tumours in this subgroup.

  6. [Parental cancer--parents ways of coping, family functioning, and psychosocial adjustment of dependent children].

    Science.gov (United States)

    Krattenmacher, Thomas; Kühne, Franziska; Führer, Daniel; Ernst, Johanna; Brähler, Elmar; Herzog, Wolfgang; von Klitzing, Kai; Flechtner, Hans-Henning; Bergelt, Corinna; Romer, Georg; Möller, Birgit

    2012-01-01

    Children exposed to parental cancer have an increased risk of mental health problems. However, the parental illness itself and its features do not predict children's psychological adjustment. Parent- and family-related factors are more predictive for children's well-being and the incidence of psychopathological symptoms, respectively. This study focuses on parental ways of coping with illness from both, the ill and healthy parent's perspective, and the relationship with family functioning and children's adjustment. Results show a significant impact of parental coping styles on children's health-related quality of life and psychopathological symptoms and, furthermore, that this relationship is mediated by aspects of family functioning. This study support the importance of family systems approaches. Implications for further studies and practical issues are discussed. PMID:22950338

  7. Recommendations to improve identification of hereditary and familial colorectal cancer in Europe

    DEFF Research Database (Denmark)

    Vasen, H F A; Möslein, G; Alonso, A;

    2010-01-01

    the general population. In almost all countries, the family history is assessed when a patient visits a general practitioner or hospital. However, the quality of family history taking was felt to be rather poor. Microsatellite instability testing (MSI) or immunohistochemical analysis (IHC) of CRC are usually...... recommended as tools to select high-risk patients for genetic testing and are performed in most countries in patients suspected of Lynch syndrome. In one country, IHC was recommended in all new cases of CRC. In most countries there are no specific programs on cancer genetics in the teaching curriculum....... Immunohistochemical analysis or MSI-analysis of all CRCs may be an effective tool for identifying all Lynch syndrome families. The cost-effectiveness of this approach should be further evaluated. All countries with a CRC population screening program should obtain a full family history as part of patient assessment....

  8. Recurrent BRCA1 and BRCA2 mutations in breast cancer patients of African ancestry.

    Science.gov (United States)

    Zhang, Jing; Fackenthal, James D; Zheng, Yonglan; Huo, Dezheng; Hou, Ningqi; Niu, Qun; Zvosec, Cecilia; Ogundiran, Temidayo O; Hennis, Anselm J; Leske, Maria Cristina; Nemesure, Barbara; Wu, Suh-Yuh; Olopade, Olufunmilayo I

    2012-07-01

    Recurrent mutations constituted nearly three quarters of all BRCA1 mutations and almost half of all BRCA2 mutations identified in the first cohort of the Nigerian Breast Cancer Study. To further characterize breast/ovarian cancer risks associated with BRCA1/BRCA2 mutations in the African diaspora, we genotyped recurrent mutations among Nigerian, African American, and Barbadian breast cancer patients. A replication cohort of 356 Nigerian breast cancer patients was genotyped for 12 recurrent BRCA1/2 mutant alleles (Y101X, 1742insG, 4241delTG, M1775R, 4359insC, C64Y, 1623delTTAAA, Q1090X, and 943ins10 from BRCA1, and 1538delAAGA, 2630del11, and 9045delGAAA from BRCA2) by means of SNaPshot followed by direct sequencing or by direct sequencing alone. In addition, 260 African Americans and 118 Barbadians were genotyped for six of the recurrent BRCA1 mutations by SNaPshot assay. Of all the BRCA1/2 recurrent mutations we identified in the first cohort, six were identified in 11 patients in the replication study. These mutation carriers constitute 3.1 % [95 % Confidence Interval (CI) 1.6-5.5 %] of the replication cohort. By comparison, 6.9 % (95 % CI 4.7-9.7 %) of the discovery cohort carried BRCA1/2 recurrent mutations. For the subset of recurrent mutations we tested in breast cancer cases from Barbados or the United States, only two 943ins10 carriers were identified in African Americans. Nigerian breast cancer patients from Ibadan carry a broad and unique spectrum of BRCA1/2 mutations. Our data suggest that BRCA1/2 mutation testing limited to recurrent mutations is not sufficient to understand the BRCA1/2-associated breast cancer risk in African populations in the diaspora. As the cost of Sanger sequencing is considerably reduced, deploying innovative technologies such as high throughput DNA sequencing of BRCA1/2 and other cancer susceptibility genes will be essential for identifying high-risk individuals and families to reduce the burden of aggressive early onset breast

  9. FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Cetta

    2015-01-01

    Full Text Available Familial Nonmedullary Thyroid Carcinoma (FNMTC makes up to 5–10% of all thyroid cancers, also including those FNMTC occurring as a minor component of familial cancer syndromes, such as Familial Adenomatous Polyposis (FAP. We give evidence that this extracolonic manifestation of FAP is determined by the same germline mutation of the APC gene responsible for colonic polyps and cancer but also shows some unusual features (F : M ratio = 80 : 1, absence of LOH for APC in the thyroid tumoral tissue, and indolent biological behaviour, despite frequent multicentricity and lymph nodal involvement, suggesting that the APC gene confers only a generic susceptibility to thyroid cancer, but perhaps other factors, namely, modifier genes, sex-related factors, or environmental factors, are also required for its phenotypic expression. This great variability is against the possibility of classifying all FNMTC as a single entity, not only with a unique or prevalent causative genetic factor, but also with a unique or common biological behavior and a commonly dismal prognosis. A new paradigm is also suggested that could be useful (1 for a proper classification of FAP associated PTC within the larger group of FNMTC and (2 for making inferences to sporadic carcinogenesis, based on the lesson from FAP.

  10. Needs of family caregivers of advanced cancer patients: a survey in Shanghai of China.

    Science.gov (United States)

    Cui, J; Song, L J; Zhou, L J; Meng, H; Zhao, J J

    2014-07-01

    It is important to understand the unmet needs of family caregivers of advanced cancer patients for developing and refining services to address the identified gaps in cancer care. To explore their needs in Chinese mainland and the possible factors associated with their needs, a self-developed questionnaire was used to survey a sample of 649 participants in 15 hospitals of Shanghai. The data were analysed using descriptive statistics, factor analysis, t-test, one-way ANOVA, and Fishers least significant difference t-test. All statistical analyses were performed using SPSS 13.0. Seven dimensions of needs (maintaining health, support from healthcare professionals, knowledge about the disease and treatment, support on funeral, information on hospice care, psychological support for patients and symptoms control for patients) were extracted from the results by factor analysis. The dimension with the highest score was 'knowledge about the disease and treatment' (4.37), and that with the lowest score named 'support on funeral' (2.85). The results showed that the factors including burden of payment for treatment, former caregiving experience of family caregivers and length of caregiving time were associated with their needs. Cancer services need to consider how to tailor resources and interventions to meet these needs of family caregivers of advanced cancer patients.

  11. Support after the completion of cancer treatment: perspectives of Australian adolescents and their families.

    Science.gov (United States)

    Wakefield, C E; McLoone, J; Butow, P; Lenthen, K; Cohn, R J

    2013-07-01

    Young people recovering from cancer may lack adequate support post-treatment, yet little is known about the types of support and information young Australians and their families need. This study investigated adolescent/young adult cancer survivors' and their families' perceptions of care and support needs after completing cancer treatment. Seventy semi-structured interviews were conducted with 19 survivors (mean age 16.1 years), 21 mothers, 15 fathers and 15 siblings. Interviews were recorded, transcribed and analysed using the conceptual framework of Miles and Huberman. Post-treatment, participants regarded medical staff positively but were reluctant to ask for their help fearing it may deflect resources away from patients still receiving treatment. Appraisals of social workers' and psychologists' support post-treatment were mixed. Formal emotional support was rarely accessed and participants reported that any additional funds should be directed to greater psychological support in this period. Participants also reported the need for additional financial support post-treatment. Clinicians need to be aware that while young people and their families may not demand support post-treatment, they may 'suffer in silence' or burden family members and friends with the responsibility of providing emotional support, though they may be experiencing distress also. PMID:23730980

  12. Evaluation of the Families SHARE workbook: an educational tool outlining disease risk and healthy guidelines to reduce risk of heart disease, diabetes, breast cancer and colorectal cancer

    OpenAIRE

    Koehly, Laura M.; Morris, Bronwyn A.; Skapinsky, Kaley; Goergen, Andrea; Ludden, Amanda

    2015-01-01

    Background Common diseases such as heart disease, diabetes, and cancer are etiologically complex with multiple risk factors (e.g., environment, genetic, lifestyle). These risk factors tend to cluster in families, making families an important social context for intervention and lifestyle-focused disease prevention. The Families Sharing Health Assessment and Risk Evaluation (SHARE) workbook was designed as an educational tool outlining family health history based risk of heart disease, type 2 d...

  13. Family-oriented psychosocial intervention in children with cancer: A systematic review

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    Leila Ostadhashemi

    2016-09-01

    Full Text Available Introduction: In recent years, evidence has shown the growing trend of published studies on family-oriented interventions in children with cancer. Besides shedding light on the current status of knowledge, a review of the existing evidence can serve an effective step toward designing and implementing appropriate interventions in this domain. Methods: This systematic review was carried out to categorize and report the findings of all types of psychosocial interventions on the family caregivers of children with cancer. The English keywords "family career", "family caregiver", “children with cancer", "psychosocial", "intervention”, “educational", and "childhood cancer" were searched in CINAHL, Web of Science (ISI, PsychINFO, Pubmed and Scopus databanks, and equivalent Persian keywords were searched in the SID of Jihad University, IRANDOC, and IranPsych and Magiran databanks. From among 819 papers found between 1994 and 2014, a total of 17 articles were included in the study after qualitative evaluation. Results: Interventions were often performed on mothers and indicated various interventional approaches. The majority of the interventions were cognitive-behavioral which were reported to be effective in improving the measured criteria such as increasing the quality of life, decreasing emotional distress, anxiety and depression, and increasing adaptive behaviors. Conclusion: The findings were generally reported to be hopeful and most of interventions were reported to have positive effects on the participants, among which behavioral-cognitive interventions were found to show the strongest evidence. Supportive interventions must be considered as an indispensable part of care for children with cancer.

  14. Considerations of Culture and Social Class for Families Facing Cancer: The Need for a New Model for Health Promotion and Psychosocial Intervention

    Science.gov (United States)

    Marshall, Catherine A.; Larkey, Linda K.; Curran, Melissa A.; Weihs, Karen L.; Badger, Terry A.; Armin, Julie; García, Francisco

    2012-01-01

    Cancer is a family experience, and family members often have as much, or more, difficulty in coping with cancer as does the person diagnosed with cancer. Using both family systems and sociocultural frameworks, we call for a new model of health promotion and psychosocial intervention that builds on the current understanding that family members, as well as the individuals diagnosed with cancer, are themselves survivors of cancer. We argue that considering culture, or the values, beliefs, and customs of the family, including their choice of language, is necessary to understand fully a family’s response to cancer. Likewise, acknowledging social class is necessary to understand how access to, and understanding of, otherwise available interventions for families facing cancer can be limited. Components of the model as conceptualized are discussed and provide guidance for psychosocial cancer health disparities research and the development of family-focused, strength-based, interventions. PMID:21688902

  15. The Occurrence and Contribution of Germline BRCA1/2 Sequence Alterations in Iranian Patients With Breast Cancer

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    Zeinali S

    2011-12-01

    Full Text Available Background: Breast cancer is the most common form of hereditary cancer worldwide and is an important cause of morbidity and mortality. Approximately 5-10% of breast and ovarian cancers are due to the highly penetrating germline mutations in cancer predisposing genes. Two genes, BRCA1 and BRCA2, account for at least half of these cases. The demand for BRCA1 and BRCA2 mutation screening is rapidly increasing as their identification will affect the medical management of people at increased risk for the disease. Therefore, the aim of this study was to investigate BRCA1/2 mutations in 100 high risk Iranian families.Methods: One hundred families who met the minimal risk factors for breast/ovarian cancer were screened among the families referred to Kawsar Human Genetics Research Center for the diseases in 2009-2011. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened for by direct sequencing and MLPA in both patients and the controls.Results: In the present study, we could detect the following novel mutations: p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Asn1403Asp, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Leu6Val, p.Arg7Cys, p.Leu15Ile, p.Ser177Thr, IVS7+83(-TT, IVS8 -70(-CATT, IVS2+9(G>C, IVS1-20(G>A, IVS1-8(A>G, p.Met1Ile, IVS2+24(A>G, IVS5-8 (A>G, IVS2(35-39TTcctatGAT, IVS13+9 G>C in BRCA1 and p.Glu1391Gly, p. Val1852Ile, IVS6-70(T>G, 1994-1995 (InsA in BRCA2.Conclusion: Ten mutations seemed to be pathogenic and the disease-causing mutations were seen in 16% of the families. In addition, from the total number of substitutions and reassortments (42, 80% related to BRCA1 and 20% to mutations in BRCA2 genes.

  16. Dyadic associations between cancer-related stress and fruit and vegetable consumption among colorectal cancer patients and their family caregivers.

    Science.gov (United States)

    Shaffer, Kelly M; Kim, Youngmee; Llabre, Maria M; Carver, Charles S

    2016-02-01

    This study examined how stress from cancer affects fruit and vegetable consumption (FVC) in cancer patients and their family caregivers during the year following diagnosis. Colorectal cancer patients and their caregivers (92 dyads) completed questionnaires at two (T1), six (T2), and 12 months post-diagnosis (T3). Individuals reported perceived cancer-related stress (CRS) at T1 and days of adequate FVC at T1 through T3. Both patients and caregivers reported inadequate FVC during the first year post-diagnosis. Latent growth modeling with actor-partner interdependence modeling revealed that, at T1, one's own greater CRS was associated with one's partner having fewer concurrent days of adequate FVC (ps = .01). Patients' greater CRS predicted their own more pronounced rebound pattern in FVC (p = .01); both patients' and caregivers' CRS marginally predicted their partners' change in FVC (p = .09). Findings suggest that perceived stress from cancer hinders FVC around the diagnosis, but motivates positive dietary changes by the end of the first year.

  17. Radiation dose to family members of hyperthyroidism and thyroid cancer patients treated with 131I

    International Nuclear Information System (INIS)

    The thermoluminescence dosemeter (TLD) was used for measuring radiation dose to family members of thyrotoxicosis and thyroid cancer patients treated with 131I using CaSO4:Dy discs. There were 45 family members of thyrotoxicosis patients, who were divided into two groups with 22 in the first and 23 in the second group. Radiation safety instructions were the same for both the groups except in the second group where the patients were advised to use a separate bed at home for the first 3 d of dose administration. An activity ranging from 185 to 500 MBq was administered to these patients. The whole-body dose to family members ranged from 0.4 to 2.4 mSv (mean 1.1 mSv) in the first group and 0-1.9 mSv (mean 0.6 mSv) in the second group. A total of 297 family members of thyroid cancer patients were studied for whole-body dose estimation. An activity ranging from 0.925 to 7.4 GBq was administered to the thyroid cancer patients. The family members were divided into three groups depending upon the mode of transport and facilities available at home to avoid close proximity with the patient. Group A with 25 family members received a dose ranging from 0 to 0.9 mSv (mean 0.4 mSv), group B with 96 family members received a dose ranging from 0 to 8.5 mSv (mean 0.8 mSv) and group C with 176 family members received a dose ranging from 0 to 5.0 mSv (mean 0.8 mSv). The thyroid monitoring was also done in 103 family members who attended the patients in isolation wards for >2 d. Thyroid dose in them ranged from 0 to 2.5 mGy (mean 0.1 mGy). (authors)

  18. No germline mutations in the histone acetyltransferase gene EP300 in BRCA1 and BRCA2 negative families with breast cancer and gastric, pancreatic, or colorectal cancer

    International Nuclear Information System (INIS)

    Mutations in BRCA1, BRCA2, ATM, TP53, CHK2 and PTEN account for many, but not all, multiple-case breast and ovarian cancer families. The histone acetyltransferase gene EP300 may function as a tumour suppressor gene because it is sometimes somatically mutated in breast, colorectal, gastric and pancreatic cancers, and is located on a region of chromosome 22 that frequently undergoes loss of heterozygosity in many cancer types. We hypothesized that germline mutations in EP300 may account for some breast cancer families that include cases of gastric, pancreatic and/or colorectal cancer. We screened the entire coding region of EP300 for mutations in the youngest affected members of 23 non-BRCA1/BRCA2 breast cancer families with at least one confirmed case of gastric, pancreatic and/or colorectal cancer. These families were ascertained in Australia through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. Denaturing HPLC analysis identified a heterozygous alteration at codon 211, specifically a GGC to AGC (glycine to serine) alteration, in two individuals. This conservative amino acid change was not within any known functional domains of EP300. The frequency of the Ser211 variant did not differ significanlty between a series of 352 breast cancer patients (4.0%) and 254 control individuals (2.8%; P = 0.5). The present study does not support a major role for EP300 mutations in breast and ovarian cancer families with a history of gastric, pancreatic and/or colorectal cancer

  19. The meaning and validation of social support networks for close family of persons with advanced cancer

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    Sjolander Catarina

    2012-09-01

    Full Text Available Abstract Background To strengthen the mental well-being of close family of persons newly diagnosed as having cancer, it is necessary to acquire a greater understanding of their experiences of social support networks, so as to better assess what resources are available to them from such networks and what professional measures are required. The main aim of the present study was to explore the meaning of these networks for close family of adult persons in the early stage of treatment for advanced lung or gastrointestinal cancer. An additional aim was to validate the study’s empirical findings by means of the Finfgeld-Connett conceptual model for social support. The intention was to investigate whether these findings were in accordance with previous research in nursing. Methods Seventeen family members with a relative who 8–14 weeks earlier had been diagnosed as having lung or gastrointestinal cancer were interviewed. The data were subjected to qualitative latent content analysis and validated by means of identifying antecedents and critical attributes. Results The meaning or main attribute of the social support network was expressed by the theme Confirmation through togetherness, based on six subthemes covering emotional and, to a lesser extent, instrumental support. Confirmation through togetherness derived principally from information, understanding, encouragement, involvement and spiritual community. Three subthemes were identified as the antecedents to social support: Need of support, Desire for a deeper relationship with relatives, Network to turn to. Social support involves reciprocal exchange of verbal and non-verbal information provided mainly by lay persons. Conclusions The study provides knowledge of the antecedents and attributes of social support networks, particularly from the perspective of close family of adult persons with advanced lung or gastrointestinal cancer. There is a need for measurement instruments that could

  20. Targeted therapy for hereditary cancer syndromes: hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Cancer genetics has rapidly evolved in the last two decades. Understanding and exploring the several genetic pathways in the cancer cell is the foundation of targeted therapy. Several genomic aberrations have been identified and their role in carcinogenesis is being explored. In contrast to most cancers where these mutations are acquired, patients with hereditary cancer syndromes have inherited genomic aberrations. The understanding of the molecular pathobiology in hereditary cancer syndromes has advanced dramatically. In addition, many molecularly targeted therapies have been developed that could have potential roles in the treatment of patients with hereditary cancer syndromes. In this review, we outline the presentation, molecular biology, and possible targeted therapies for two of the most widely recognized hereditary cancer syndromes -- hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). We will also discuss other syndromes such as familial adenomatous polyposis and Li-Fraumeni syndrome (TP53). PMID:25549704

  1. BRCA1 status in Pakistani breast cancer patients with moderate family history

    International Nuclear Information System (INIS)

    Objective: To determine BRCA1 status in breast carcinoma patients of Pakistani origin. Study Design: Observational study. Place and Duration of Study: The Oncology Clinics of the Aga Khan University Hospital, Karachi, between May 2005 and December 2009. Methodology: Fifty three breast cancer patients based on clinical and laboratory diagnosis were recruited for this study. Moderate family history was defined as having a close relative (mother, daughter, sister) diagnosed with breast cancer under 45 years. Peripheral blood samples were collected from each patient in a 5 ml tube containing EDTA as anticoagulant. Subsequent to DNA extraction, mutational analysis of BRCA1 exons 2, 5, 6, 16, 20 and 22 was carried out using single strand conformation polymorphism (SSCP) assay while protein truncation test (PTT) was used to examine mutations in exon 11. All BRCA1 sequence variants were confirmed by DNA sequencing. Results: Twenty-three patients were diagnosed with early onset breast cancer, 30 patients had moderate family history. At the time of diagnosis, the median age of enrolled patients was 39 years (range 24-65 years). Out of 53 patients, analyzed by SSCP assay, mobility shift was detected in exon 6, 16 and 20 of three patients, whereas one patient was tested positive for mutation in exon 11 by PTT assays. All patients with BRCA1 mutations were further confirmed by DNA sequencing analysis. In exon 16 c.4837A > G was confirmed, which is a common polymorphism reported in several populations including Asians. Moreover, mutations in exon 6 (c.271T > G), exon 20 (c.5231 del G) and exon 11 (c.1123 T > G) were reported first time in the Pakistani population. Several BRCA1 mutations were observed in Pakistani breast cancer patients with moderate family history. Therefore, mutation-based genetic counselling for patients with moderate family history can facilitate management, if one first or second degree relative or early onset disease is apparent. (author)

  2. Interaction of Dietary Fatty Acids with Tumour Necrosis Factor Family Cytokines during Colon Inflammation and Cancer

    OpenAIRE

    Jiřina Hofmanová; Nicol Straková; Alena Hyršlová Vaculová; Zuzana Tylichová; Barbora Šafaříková; Belma Skender; Alois Kozubík

    2014-01-01

    Intestinal homeostasis is precisely regulated by a number of endogenous regulatory molecules but significantly influenced by dietary compounds. Malfunction of this system may result in chronic inflammation and cancer. Dietary essential n-3 polyunsaturated fatty acids (PUFAs) and short-chain fatty acid butyrate produced from fibre display anti-inflammatory and anticancer activities. Both compounds were shown to modulate the production and activities of TNF family cytokines. Cytokines from the ...

  3. Higher cytoplasmic and nuclear poly(ADP-ribose) polymerase expression in familial than in sporadic breast cancer.

    Science.gov (United States)

    Klauke, Marie-Luise; Hoogerbrugge, Nicoline; Budczies, Jan; Bult, Peter; Prinzler, Judith; Radke, Cornelia; van Krieken, J Han J M; Dietel, Manfred; Denkert, Carsten; Müller, Berit Maria

    2012-10-01

    Poly(ADP-ribose) polymerase 1 (PARP) is a key element of the single-base excision pathway for repair of DNA single-strand breaks. To compare the cytoplasmic and nuclear poly(ADP-ribose) expression between familial (BRCA1, BRCA2, or non BRCA1/2) and sporadic breast cancer, we investigated 39 sporadic and 39 familial breast cancer cases. The two groups were matched for hormone receptor status and human epidermal growth factor receptor 2 status. Additionally, they were matched by grading with a maximum difference of ±1 degree (e.g., G2 instead of G3). Cytoplasmic PARP (cPARP) expression was significantly higher in familial compared to sporadic breast cancer (P = 0.008, chi-squared test for trends) and a high nuclear PARP expression (nPARP) was significantly more frequently observed in familial breast cancer (64 %) compared with sporadic breast cancer (36 %) (P = 0.005, chi-squared test). The overall PARP expression was significantly higher in familial breast cancer (P = 0.042, chi-squared test). In familial breast cancer, a combination of high cPARP and high nPARP expression is the most common (33 %), whereas in sporadic breast cancer, a combination of low cPARP and intermediate nPARP expression is the most common (39 %). Our results show that the overall PARP expression in familial breast cancer is higher than in sporadic breast cancer which might suggest they might respond better to treatment with PARP inhibitors.

  4. Mutation analysis of the ATR gene in breast and ovarian cancer families

    International Nuclear Information System (INIS)

    Mutations in BRCA1, BRCA2, ATM, TP53, CHK2 and PTEN account for only 20–30% of the familial aggregation of breast cancer, which suggests the involvement of additional susceptibility genes. The ATR (ataxia-telangiectasia- and Rad3-related) kinase is essential for the maintenance of genomic integrity. It functions both in parallel and cooperatively with ATM, but whereas ATM is primarily activated by DNA double-strand breaks induced by ionizing radiation, ATR has been shown to respond to a much broader range of DNA damage. Upon activation, ATR phosphorylates several important tumor suppressors, including p53, BRCA1 and CHK1. Based on its central function in the DNA damage response, ATR is a plausible candidate gene for susceptibility to cancer. We screened the entire coding region of the ATR gene for mutations in affected index cases from 126 Finnish families with breast and/or ovarian cancer, 75 of which were classified as high-risk and 51 as moderate-risk families, by using conformation sensitive gel electrophoresis and direct sequencing. A large number of novel sequence variants were identified, four of which – Glu254Gly, Ser1142Gly, IVS24-48G>A and IVS26+15C>T – were absent from the tested control individuals (n = 300). However, the segregation of these mutations with the cancer phenotype could not be confirmed, partly because of the lack of suitable DNA samples. The present study does not support a major role for ATR mutations in hereditary susceptibility to breast and ovarian cancer

  5. Progesterone and adiponectin receptor family member 3 expression and clinical significance in breast cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Xiao-Qiang Dai; Hai-Liang Zhang; Hong-Mei Li

    2016-01-01

    Objective:To discuss progesterone and adiponectin receptor family member 3 expression and clinical significance in breast cancer tissues. Method:A total of 90 cases with breast cancer who were admitted in our hospital from Jan 2000 to Jan 2010 were selected. Meanwhile, normal tumor-adjacent breast tissues were selected as comparison. Diagnosis of all patients was confirmed by postoperative pathological examinations. Immunohistochemistry method was adopted to detect PAQR3 protein expression in breast cancer tissues and normal tumor-adjacent breast tissues and its clinical significance was discussed. Results:PAQR3 protein positive expression rate in breast cancer tissues was 25.6%, which was significantly lower than that (78.9%) in normal tumor-adjacent breast tissues;PAQR3 protein positive expression rate had nothing to do with age, tumor size, pathological types and differentiated degree of patients, but had significant correlation with TNM staging and lymphatic metastasis existence of patients. Kaplan–Meier survival analysis results showed that five years survival rate of patients with PAQR3 protein positive expression was significantly higher than whom with negative expression. Conclusion:PAQR3 protein expression in breast cancer tissues was significantly reduced, which indicated that PAQR3 protein possibly played an important role in pathogenesis of breast cancer.

  6. Sequencing analysis of SLX4/FANCP gene in Italian familial breast cancer cases.

    Directory of Open Access Journals (Sweden)

    Irene Catucci

    Full Text Available Breast cancer can be caused by germline mutations in several genes that are responsible for different hereditary cancer syndromes. Some of the genes causing the Fanconi anemia (FA syndrome, such as BRCA2, BRIP1, PALB2, and RAD51C, are associated with high or moderate risk of developing breast cancer. Very recently, SLX4 has been established as a new FA gene raising the question of its implication in breast cancer risk. This study aimed at answering this question sequencing the entire coding region of SLX4 in 526 familial breast cancer cases from Italy. We found 81 different germline variants and none of these were clearly pathogenic. The statistical power of our sample size allows concluding that in Italy the frequency of carriers of truncating mutations of SLX4 may not exceed 0.6%. Our results indicate that testing for SLX4 germline mutations is unlikely to be relevant for the identification of individuals at risk of breast cancer, at least in the Italian population.

  7. Prognostic Significance of Apoptosis Related Gene Family bcl-2 in Human Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the prognostic effect of bcl-2 oncogene and its gene family members bax, bcl-x expression in breast cancer patients. Methods: expression of bcl-2, bax proteins in 91 human breast cancer tissue sections were studied by immunohistochemical method. Bcl-x1 mRNA expression in frozen tissues from 16 breast cancer patients were detected using Northern blot method. Results: bcl-2 protein positivity was found in 60/91 (65.9%) patients, and bax positivity 59/91 (64.8%). Bcl-2 and bax expression levels were associated with apoptotic index(AI), histological grade, axillary lymph node metastasis, postoperative local recurrence and metastasis. Bcl-2 expression was related to ER positivity. In univariate analysis for disease free survival (DFS), bcl-2 and bax protein levels, and Al were all found to have prognostic value. The result of Cox's model multivariate analysis showed that bcl-2 protein level was an independent prognostic factor. In 16 frozen breast cancer tissues, 8/16(50%) had higher level of bcl-x1 mRNA, which showed correlation with bcl-2 protein expression and axillary lymph node metastasis. Conclusion: The findings indicate that dysregulated expressions of bcl-2, bax and bcl-x1 apoptosis-related genes, suggestive of serious deregulation of apoptotic process, may contribute to the biologic aggressiveness of breast cancer. Bcl-2 protein is an independent indicator of prognosis in breast cancer patients.

  8. Small Molecule Inhibitors of Bcl-2 Family Proteins for Pancreatic Cancer Therapy

    International Nuclear Information System (INIS)

    Pancreatic cancer (PC) has a complex etiology and displays a wide range of cellular escape pathways that allow it to resist different treatment modalities. Crucial signaling molecules that function downstream of the survival pathways, particularly at points where several of these pathways crosstalk, provide valuable targets for the development of novel anti-cancer drugs. Bcl-2 family member proteins are anti-apoptotic molecules that are known to be overexpressed in most cancers including PC. The anti-apoptotic machinery has been linked to the observed resistance developed to chemotherapy and radiation and therefore is important from the targeted drug development point of view. Over the past ten years, our group has extensively studied a series of small molecule inhibitors of Bcl-2 against PC and provide solid preclinical platform for testing such novel drugs in the clinic. This review examines the efficacy, potency, and function of several small molecule inhibitor drugs targeted to the Bcl-2 family of proteins and their preclinical progress against PC. This article further focuses on compounds that have been studied the most and also discusses the anti-cancer potential of newer class of Bcl-2 drugs

  9. Evolutionary origin and human-specific expansion of a cancer/testis antigen gene family.

    Science.gov (United States)

    Zhang, Qu; Su, Bing

    2014-09-01

    Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here, we presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multiexon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats. Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution. PMID:24916032

  10. Experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer

    Directory of Open Access Journals (Sweden)

    Gláucia Sousa Oliveira

    2014-04-01

    Full Text Available This is a study with the objective to know the experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer. A qualitative research, grounded on the humanization referential, made in 2013, through serialized semi-structured interviews and inductive analysis. It was approved by the Ethics and Research Committee under legal opinion no. 237,771. Seven family caregivers participated in this study in a county of southern Minas Gerais state, Brazil. Three categories emerged from the data: Relation with the disease and its treatments; Impact facing treatment and rehabilitation and Nets of support. The representation of the disease associated to finitude is reaffirmed. In order to lessen anguish and suffering, the family caregivers search support, mainly in spirituality. The impact resulting from the illness and the rehabilitation process imposes a new order to the caregivers, with personal and social renouncing, which provides a closer and more dedicated relation with the patient.

  11. Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium.

    NARCIS (Netherlands)

    Cote, M.L.; Liu, M.; Bonassi, S.; Neri, M.; Schwartz, A.G.; Christiani, D.C.; Spitz, M.R.; Muscat, J.E.; Rennert, G.; Aben, K.K.H.; Andrew, A.S.; Bencko, V.; Bickeboller, H.; Boffetta, P.; Brennan, P.; Brenner, H.; Duell, E.J.; Fabianova, E.; Field, J.K.; Foretova, L.; Friis, S.; Harris, C.C.; Holcatova, I.; Hong, Y.C.; Isla, D.; Janout, V.; Kiemeney, L.A.L.M.; Kiyohara, C.; Lan, Q.; Lazarus, P.; Lissowska, J.; Marchand, L. le; Mates, D.; Matsuo, K.; Mayordomo, J.I.; McLaughlin, J.R.; Morgenstern, H.; Mueller, H.; Orlow, I.; Park, B.J.; Pinchev, M.; Raji, O.Y.; Rennert, H.S.; Rudnai, P.; Seow, A.; Stucker, I.; Szeszenia-Dabrowska, N.; Teare, M.D.; Tjonnelan, A.; Ugolini, D.; Heijden, E. van der; Wichmann, E.; Wiencke, J.K.; Woll, P.J.; Yang, P.; Zaridze, D.; Zhang, Z.F.; Etzel, C.J.; Hung, R.J.

    2012-01-01

    BACKGROUND AND METHODS: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies i

  12. El cáncer hereditario en mujeres

    OpenAIRE

    Morales Chamorro, Rafael; Chirivella González, Isabel; Llort Pursals, Gemma; Sánchez Heras, Ana Beatriz; Serrano Blanch, Raquel; Teule Vega, Alexandre; Guillén Ponce, Carmen; Graña Suárez, Begoña

    2015-01-01

    Most cases of cancer are sporadic, whereas 5-10% are hereditary and about 20-30% of cancers tend to cluster in families. Families and individuals who are suspected of suffering from hereditary cancer need to undergo a process known as genetic counseling, which is of considerable importance in the prevention and early detection of malignant tumours. The most common hereditary cancer syndromes are: hereditary breast-ovarian cancer syndrome, familial adenomatous polyposis and Lynch syndrome. Gen...

  13. Family Life

    Science.gov (United States)

    ... Family and Friends > Family Life Request Permissions Family Life Approved by the Cancer.Net Editorial Board , 07/ ... treatment become as overwhelming for others in your life as they are for you. Understanding the potential ...

  14. Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer

    DEFF Research Database (Denmark)

    Wiklund, Erik D; Bramsen, Jesper B; Hulf, Toby;

    2011-01-01

    MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and miR-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the t...

  15. PS1-08: Genetic Service Providers Identify Barriers Related to Referral, Counseling and Testing for Familial Cancer

    OpenAIRE

    Jackson, Jody; Rolnick, Cheri; Rahm, Alanna; Nekhlyudov, Larissa; Goddard, Katrina; Field, Terry; McCarty, Catherine; Nakasato, Cynthia; ROBLIN, DOUGLAS; Anderson, Christopher; Valdez, Rodolfo

    2010-01-01

    Background and Aims: Little of what we know about the use of family history and genetic risk assessment services has been gathered from those engaged in counseling. To fill this gap, we conducted a survey to understand the processes of identifying and referring high-risk patients for genetic counseling and testing for familial cancer from the perspective of genetic service providers.

  16. A compendium of familial relative risks of cancer among first degree relatives: A population-based study

    NARCIS (Netherlands)

    Zeegers, M.P.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2008-01-01

    Familial clustering of cancer is expected to occur at practically all anatomical sites. However, few studies have had sufficient size to investigate different sites simultaneously and with adjustment for confounders. We evaluated familial clustering in the Netherlands Cohort Study in which 120,852 m

  17. Low prevalence of germline hMSH6 mutations in colorectal cancer families from Spain

    Institute of Scientific and Technical Information of China (English)

    Ana Sánchez de Abajo; Trinidad Caldes; Miguel de la Hoya; Alicia Tosar; Javier Godino; Juan Manuel Fernández; Jose Lopez Asenjo; Beatriz Perez Villamil; Pedro Perez Segura; Eduardo Diaz-Rubio

    2005-01-01

    AIM: To investigate the prevalence and penetrance of hMSH6 mutations in Spanish HNPCC families that was negative for mutation in hMLH1 or hMSH2.METHODS: We used PCR-based DGGE assay and direct Sequencing to screen for hMSH6 gene in 91 HNPCC families.RESULTS: we have identified 10 families with germ-line mutations in the DNA sequence. These mutations included two intronic variation, three missense mutation, one nonsense mutation, and four silent mutations. Among the 10 germ-line mutations identified in the Spanish cohort,8 were novel, perhaps, suggesting different mutational spectra in the Spanish population. Detailed pedigrees were constructed for the three families with a possible pathogenic hMSH6 mutation. The two silent mutations H388H and L758L, detected in a person affected of colorectal cancer at age 29, produce loss of the wild-type allele in the tumor sample. Immunohistochemical analysis showed that expression of MSH6 protein was lost only in the tumors from the carriers of V878A and Q263X mutations.CONCLUSION: Altogether, our results indicate that disease-causing germ-line mutations of hMSH6 are very less frequent in Spanish HNPCC families.

  18. Differential effects of wine consumption on colorectal cancer outcomes based on family history of the disease.

    Science.gov (United States)

    Zell, Jason A; McEligot, Archana J; Ziogas, Argyrios; Holcombe, Randall F; Anton-Culver, Hoda

    2007-01-01

    Potentially favorable effects of wine consumption on colorectal cancer (CRC) incidence have been reported, but effects on clinical outcomes are unknown. This case-only analysis was designed to investigate outcomes among familial (n = 141) and sporadic (n = 358) CRC patients enrolled in the University of California Irvine CRC gene-environment study during 1994-1996 based on their reported frequency of wine consumption in the year prior to diagnosis. Cases were categorized as either regular or infrequent wine consumers. Univariate survival rate analyses were estimated using the Kaplan and Meier method and log-rank test. Multivariate survival analyses were performed using Cox proportional hazards ratios (HRs). Earlier stage at presentation (P = 0.034) was noted for familial (but not sporadic) CRC cases reporting regular wine consumption. An overall survival (OS) benefit was observed for familial (but not sporadic) CRC cases that were regular (10-yr OS = 75%) versus infrequent wine consumers (10-yr OS = 47%; P = 0.002). This survival improvement for familial CRC cases remained after adjustment for age, stage, treatment, and other clinically relevant factors (HR = 0.50, 95% confidence interval = 0.25-0.99). Our findings implicate favorable effects of wine consumption on stage at presentation and survival in CRC, selectively among familial CRC cases.

  19. Family caregiver perspective-taking and accuracy in estimating cancer patient symptom experiences.

    Science.gov (United States)

    Lobchuk, Michelle M; Vorauer, Jacquie D

    2003-12-01

    As family caregivers assume more prominent roles in the provision of home care to persons with serious illness, investigators must test the effectiveness of novel interventions to facilitate family caring for cancer patients. This article is based on results derived from a larger study carried out in Canada that was designed to compare 98 advanced cancer patient and family caregiver perceptions of 32 patient symptom experiences as captured by the Memorial Symptom Assessment Scale. We examined two main questions: (1) whether "natural" family caregivers' perceptions of patient lack of energy and worrying are more closely related to a self- or patient-oriented viewpoint and (2) whether induced "imagine-patient" perspective-taking can assist caregivers to achieve better perceptual accuracy. The caregiver's natural responses to neutral instructions that neither encouraged nor discouraged perspective-taking served as the baseline comparison with three other instructional sets, in which caregivers were prompted to: (1) provide a self-report on their own symptom experiences, (2) imagine how they would feel in the patient's situation (imagine-self), or (3) imagine how the patient would respond to his or her symptom situation (imagine-patient). Findings suggested that the family caregivers' natural judgments correspond most closely to what they do under an imagine-patient set than to what they do under any other set. Findings with respect to accuracy indicated that instructions to imagine the patient's perspective helped to prompt adjustments down from a self-oriented viewpoint, although definitive conclusions were precluded by difficulties with order effects.

  20. Frequency of the ATM IVS10-6T→G variant in Australian multiple-case breast cancer families

    International Nuclear Information System (INIS)

    Germline mutations in the genes BRCA1 and BRCA2 account for only a proportion of hereditary breast cancer, suggesting that additional genes contribute to hereditary breast cancer. Recently a heterozygous variant in the ataxia–telangiectasia mutated (ATM) gene, IVS10-6T→G, was reported by an Australian multiple-case breast cancer family cohort study (the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer) to confer a substantial breast cancer risk. Although this variant can result in a truncated ATM product, its clinical significance as a high-penetrance breast cancer allele or its role as a low-penetrance risk-modifier is controversial. We determined the frequency of ATM IVS10-6T→G variants in a cohort of individuals affected by breast and/or ovarian cancer who underwent BRCA1 and BRCA2 genetic testing at four major Australian familial cancer clinics. Seven of 495 patients (1.4%) were heterozygous for the IVS10-6T→G variant; the carrier rate in unselected Australian women with no family history of breast cancer is reported to be 6 of 725 (0.83%) (P = 0.4). Two of the seven probands also harboured a pathogenic BRCA1 mutation and one patient had a BRCA1 unclassified variant of uncertain significance. These findings indicate that the ATM IVS10-6T→G variant does not seem to occur at a significantly higher frequency in affected individuals from high-risk families than in the general population. A role for this variant as a low-penetrance allele or as a modifying gene in association with other genes (such as BRCA1) remains possible. Routine testing for ATM IVS10-6T→G is not warranted in mutation screening of affected individuals from high-risk families

  1. A Novel WRN Frameshift Mutation Identified by Multiplex Genetic Testing in a Family with Multiple Cases of Cancer.

    Science.gov (United States)

    Yang, Liu; Wang, Guosheng; Zhao, Xinyi; Ye, Song; Shen, Peng; Wang, Weilin; Zheng, Shusen

    2015-01-01

    Next-generation sequencing technology allows simultaneous analysis of multiple susceptibility genes for clinical cancer genetics. In this study, multiplex genetic testing was conducted in a Chinese family with multiple cases of cancer to determine the variations in cancer predisposition genes. The family comprises a mother and her five daughters, of whom the mother and the eldest daughter have cancer and the secondary daughter died of cancer. We conducted multiplex genetic testing of 90 cancer susceptibility genes using the peripheral blood DNA of the mother and all five daughters. WRN frameshift mutation is considered a potential pathogenic variation according to the guidelines of the American College of Medical Genetics. A novel WRN frameshift mutation (p.N1370Tfs*23) was identified in the three cancer patients and in the youngest unaffected daughter. Other rare non-synonymous germline mutations were also detected in DICER and ELAC2. Functional mutations in WRN cause Werner syndrome, a human autosomal recessive disease characterized by premature aging and associated with genetic instability and increased cancer risk. Our results suggest that the WRN frameshift mutation is important in the surveillance of other members of this family, especially the youngest daughter, but the pathogenicity of the novel WRN frameshift mutation needs to be investigated further. Given its extensive use in clinical genetic screening, multiplex genetic testing is a promising tool in clinical cancer surveillance.

  2. Australian clinicians and chemoprevention for women at high familial risk for breast cancer

    Directory of Open Access Journals (Sweden)

    Keogh Louise A

    2009-05-01

    Full Text Available Abstract Objectives Effective chemoprevention strategies exist for women at high risk for breast cancer, yet uptake is low. Physician recommendation is an important determinant of uptake, but little is known about clinicians' attitudes to chemoprevention. Methods Focus groups were conducted with clinicians at five Family Cancer Centers in three Australian states. Discussions were recorded, transcribed and analyzed thematically. Results Twenty three clinicians, including genetic counselors, clinical geneticists, medical oncologists, breast surgeons and gynaecologic oncologists, participated in six focus groups in 2007. The identified barriers to the discussion of the use of tamoxifen and raloxifene for chemoprevention pertained to issues of evidence (evidence for efficacy not strong enough, side-effects outweigh benefits, oophorectomy superior for mutation carriers, practice (drugs not approved for chemoprevention by regulatory authorities and not government subsidized, chemoprevention not endorsed in national guidelines and not many women ask about it, and perception (clinicians not knowledgeable about chemoprevention and women thought to be opposed to hormonal treatments. Conclusion The study demonstrated limited enthusiasm for discussing breast cancer chemoprevention as a management option for women at high familial risk. Several options for increasing the likelihood of clinicians discussing chemoprevention were identified; maintaining up to date national guidelines on management of these women and education of clinicians about the drugs themselves, the legality of "off-label" prescribing, and the actual costs of chemopreventive medications.

  3. Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients.

    Science.gov (United States)

    Benitez-Buelga, C; Sanchez-Barroso, L; Gallardo, M; Apellániz-Ruiz, María; Inglada-Pérez, L; Yanowski, K; Carrillo, J; Garcia-Estevez, L; Calvo, I; Perona, R; Urioste, M; Osorio, A; Blasco, M A; Rodriguez-Antona, C; Benitez, J

    2015-01-01

    Recently, we observed that telomeres of BRCA1/2 mutation carriers were shorter than those of controls or sporadic breast cancer patients, suggesting that mutations in these genes might be responsible for this event. Given the contradictory results reported in the literature, we tested whether other parameters, such as chemotherapy, could be modifying telomere length (TL). We performed a cross-sectional study measuring leukocyte TL of 266 sporadic breasts cancer patients treated with first-line chemotherapy, with a median follow-up of 240 days. Additionally, we performed both cross-sectional and longitudinal studies in a series of 236 familial breast cancer patients that included affected and non-affected BRCA1/2 mutation carriers. We have measured in leukocytes from peripheral blood: the TL, percentage of short telomeres (cases we found that chemotherapy exerts a transient telomere shortening effect (around 2 years) that varies depending on the drug combination. In familial cases, only patients receiving treatment were associated with telomere shortening but they recovered normal TL after a period of 2 years. Chemotherapy affects TL and should be considered in the studies that correlate TL with disease susceptibility. PMID:25528024

  4. A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer

    DEFF Research Database (Denmark)

    Mesher, David; Dove-Edwin, Isis; Sasieni, Peter;

    2014-01-01

    centers. DNA mismatch repair deficiency was excluded by genetic testing. Families were classified as FCC type X if they fulfilled the original Amsterdam criteria (AC) and late onset (LOFCC) if they fulfilled the AC apart from not having a cancer aged under 50. The most advanced findings on colonoscopy...... were analyzed. One thousand five hundred eighty-five individuals (median age 47.3, 44% male) from 530 FCC families (349 FCC type X) underwent a total of 4,992 colonoscopies with 7,904 patient-years of follow-up. Results for FCC type X and LOFCC were very similar. At baseline, 22 prevalent asymptomatic...... colorectal cancers were diagnosed, 120 (7.6%) individuals had high-risk adenomas and 225 (14.2%) simple adenomas. One thousand eighty-eight individuals had a further colonoscopy (median follow-up of 6.2 years). Of nine individuals diagnosed with cancer, eight had a previous history of at least one polyp...

  5. Asymmetry in family history implicates nonstandard genetic mechanisms: application to the genetics of breast cancer.

    Directory of Open Access Journals (Sweden)

    Clarice R Weinberg

    2014-03-01

    Full Text Available Genome-wide association studies typically target inherited autosomal variants, but less studied genetic mechanisms can play a role in complex disease. Sex-linked variants aside, three genetic phenomena can induce differential risk in maternal versus paternal lineages of affected individuals: 1. maternal effects, reflecting the maternal genome's influence on prenatal development; 2. mitochondrial variants, which are inherited maternally; 3. autosomal genes, whose effects depend on parent of origin. We algebraically show that small asymmetries in family histories of affected individuals may reflect much larger genetic risks acting via those mechanisms. We apply these ideas to a study of sisters of women with breast cancer. Among 5,091 distinct families of women reporting that exactly one grandmother had breast cancer, risk was skewed toward maternal grandmothers (p<0.0001, especially if the granddaughter was diagnosed between age 45 and 54. Maternal genetic effects, mitochondrial variants, or variant genes with parent-of-origin effects may influence risk of perimenopausal breast cancer.

  6. Coaching Family Caregivers to Become Better Problem Solvers When Caring for Persons with Advanced Cancer.

    Science.gov (United States)

    Dionne-Odom, J Nicholas; Lyons, Kathleen D; Akyar, Imatullah; Bakitas, Marie A

    2016-01-01

    Family caregivers of persons with advanced cancer often take on responsibilities that present daunting and complex problems. Serious problems that go unresolved may be burdensome and result in negative outcomes for caregivers' psychological and physical health and affect the quality of care delivered to the care recipients with cancer, especially at the end of life. Formal problem-solving training approaches have been developed over the past several decades to assist individuals with managing problems faced in daily life. Several of these problem-solving principles and techniques were incorporated into ENABLE (Educate, Nurture, Advise, Before Life End), an "early" palliative care telehealth intervention for individuals diagnosed with advanced cancer and their family caregivers. A hypothetical case resembling the situations of actual caregiver participants in ENABLE that exemplifies the complex problems that caregivers face is presented, followed by presentation of an overview of ENABLE's problem-solving key principles, techniques, and steps in problem-solving support. Though more research is needed to formally test the use of problem-solving support in social work practice, social workers can easily incorporate these techniques into everyday practice. PMID:27143574

  7. Clinical importance of Familial Pancreatic Cancer Registry in Japan: a report from kick-off meeting at International Symposium on Pancreas Cancer 2012.

    Science.gov (United States)

    Wada, Keita; Takaori, Kyoichi; Traverso, L William; Hruban, Ralph H; Furukawa, Toru; Brentnall, Teresa A; Hatori, Takashi; Sano, Keiji; Takada, Tadahiro; Majima, Yoshiyuki; Shimosegawa, Tooru

    2013-08-01

    Pancreatic cancer is still a highly lethal disease with a 5-year survival rate of approximately 5 %. Early detection offers one of the best hopes for improving survival. Previous cohort studies and case-control studies showed that 4-10 % of pancreatic cancers have a hereditary basis, and individuals with a family history have an increased risk of developing pancreatic and extra-pancreatic malignancies. Since individuals with a family history of pancreatic cancer and those with a known genetic syndrome that predisposes to pancreatic cancer will be the first to benefit from early detection tests as they become available, familial pancreatic cancer (FPC) registries have been established in the US and Europe, but not yet in Japan. Such registries form the basis for epidemiological studies, clinical trials, and basic research on familial pancreatic cancer. There is a need for FPC registries in Japan as cancer risk varies among different populations and discoveries made in Western populations may not translate to the Japanese population. These registries in Japan will align with ongoing international efforts and add to a better understanding of the natural history, risk factors, screening strategies, and responsible genes, for improving survival of this dismal disease.

  8. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG families

    Directory of Open Access Journals (Sweden)

    Bailey-Wilson Joan E

    2012-06-01

    Full Text Available Abstract Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG. Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD of 1.28, and an allele-sharing lod score (LOD of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM. For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission

  9. The role of the family environment and computer-mediated social support on breast cancer patients' coping strategies.

    Science.gov (United States)

    Yoo, Woohyun; Shah, Dhavan V; Shaw, Bret R; Kim, Eunkyung; Smaglik, Paul; Roberts, Linda J; Hawkins, Robert P; Pingree, Suzanne; McDowell, Helene; Gustafson, David H

    2014-09-01

    Despite the importance of family environment and computer-mediated social support (CMSS) for women with breast cancer, little is known about the interplay of these sources of care and assistance on patients' coping strategies. To understand this relation, the authors examined the effect of family environment as a predictor of the use of CMSS groups as well as a moderator of the relation between group participation and forms of coping. Data were collected from 111 patients in CMSS groups in the Comprehensive Health Enhancement Support System "Living with Breast Cancer" intervention. Results indicate that family environment plays a crucial role in (a) predicting breast cancer patient's participation in CMSS groups and (b) moderating the effects of use of CMSS groups on breast cancer patients' coping strategies such as problem-focused coping and emotion-focused coping. PMID:24511907

  10. Evaluation and integration of cancer gene classifiers: identification and ranking of plausible drivers.

    Science.gov (United States)

    Liu, Yang; Tian, Feng; Hu, Zhenjun; DeLisi, Charles

    2015-05-11

    The number of mutated genes in cancer cells is far larger than the number of mutations that drive cancer. The difficulty this creates for identifying relevant alterations has stimulated the development of various computational approaches to distinguishing drivers from bystanders. We develop and apply an ensemble classifier (EC) machine learning method, which integrates 10 classifiers that are publically available, and apply it to breast and ovarian cancer. In particular we find the following: (1) Using both standard and non-standard metrics, EC almost always outperforms single method classifiers, often by wide margins. (2) Of the 50 highest ranked genes for breast (ovarian) cancer, 34 (30) are associated with other cancers in either the OMIM, CGC or NCG database (P plausible. Biological implications are briefly discussed. Source codes and detailed results are available at http://www.visantnet.org/misi/driver_integration.zip.

  11. Identification of 2R-ohnologue gene families displaying the same mutation-load skew in multiple cancers.

    Science.gov (United States)

    Tinti, Michele; Dissanayake, Kumara; Synowsky, Silvia; Albergante, Luca; MacKintosh, Carol

    2014-01-01

    The complexity of signalling pathways was boosted at the origin of the vertebrates, when two rounds of whole genome duplication (2R-WGD) occurred. Those genes and proteins that have survived from the 2R-WGD-termed 2R-ohnologues-belong to families of two to four members, and are enriched in signalling components relevant to cancer. Here, we find that while only approximately 30% of human transcript-coding genes are 2R-ohnologues, they carry 42-60% of the gene mutations in 30 different cancer types. Across a subset of cancer datasets, including melanoma, breast, lung adenocarcinoma, liver and medulloblastoma, we identified 673 2R-ohnologue families in which one gene carries mutations at multiple positions, while sister genes in the same family are relatively mutation free. Strikingly, in 315 of the 322 2R-ohnologue families displaying such a skew in multiple cancers, the same gene carries the heaviest mutation load in each cancer, and usually the second-ranked gene is also the same in each cancer. Our findings inspire the hypothesis that in certain cancers, heterogeneous combinations of genetic changes impair parts of the 2R-WGD signalling networks and force information flow through a limited set of oncogenic pathways in which specific non-mutated 2R-ohnologues serve as effectors. The non-mutated 2R-ohnologues are therefore potential therapeutic targets. These include proteins linked to growth factor signalling, neurotransmission and ion channels.

  12. Awareness and Perceptions of Clinical Trials in Cancer Patients and Their Families in Saudi Arabia.

    Science.gov (United States)

    Bazarbashi, Shouki; Hassan, Anees; Eldin, Ahmed Mohi; Soudy, Hussein; Hussain, Fazal

    2015-12-01

    Despite the increasing number of medical articles being published from the Middle East, clinical research is still lagging behind compared to other regions. Enrolling participants into clinical trials presents an important challenge. We wanted to explore the perception, knowledge, and willingness of cancer patients to participate in oncology clinical trials and to recommend strategies to overcome these challenges. A 31-item questionnaire was administered to cancer patients and their family members in an outpatient clinic. Two hundred four patients and family members were enrolled between December 2011 and February 2013. Fifty-eight percent of the participants were aware of clinical trials. Some misconceptions included the following: 22% believed that no clinical trials were conducted in the Arab world, 19% believed that clinical trials in the Arab world were not under any regulatory authority supervision, and 15% believed that local clinical trials are conducted on subjects without their consent. One third of patients assumed that clinical trials are executed on animals instead of humans, and greater than 40% believed that clinical trials are performed for new medications only. Finally, 61% of the survey participants who were aware of clinical trials expressed their willingness to participate in trials. This large cohort survey demonstrated that a relatively significant number of Saudi cancer patients and their families are aware of clinical trials and a similarly high number of participants are willing to participate in clinical trials. This leads us to believe that patients' awareness and perception of clinical trials are not a significant limiting factor in clinical trial recruitment in our region.

  13. Structure and Cancer Immunotherapy of the B7 Family Member B7x

    Directory of Open Access Journals (Sweden)

    Hyungjun Jeon

    2014-11-01

    Full Text Available B7x (B7-H4 or B7S1 is a member of the B7 family that can inhibit T cell function. B7x protein is absent in most normal human tissues and immune cells, but it is overexpressed in human cancers and often correlates with negative clinical outcome. The expression pattern and function of B7x suggest that it may be a potent immunosuppressive pathway in human cancers. Here, we determined the crystal structure of the human B7x immunoglobulin variable (IgV domain at 1.59 Å resolution and mapped the epitopes recognized by monoclonal antibodies. We developed an in vivo system to screen therapeutic monoclonal antibodies against B7x and found that the clone 1H3 significantly inhibited growth of B7x-expressing tumors in vivo via multiple mechanisms. Furthermore, the surviving mice given 1H3 treatment were resistant to tumor rechallenge. Our data suggest that targeting B7x on tumors is a promising cancer immunotherapy and humanized 1H3 may be efficacious for immunotherapy of human cancers.

  14. EMSY links breast cancer gene 2 to the 'Royal Family'

    International Nuclear Information System (INIS)

    Although the role of the breast cancer gene 2 (BRCA2) tumor suppressor gene is well established in inherited breast and ovarian carcinomas, its involvement in sporadic disease is still uncertain. The recent identification of a novel BRCA2 binding protein, EMSY, as a putative oncogene implicates the BRCA2 pathway in sporadic tumors. Furthermore, EMSY's binding to members of the 'Royal Family' of chromatin remodeling proteins may lead to a better understanding of the physiological function of BRCA2 and its role in chromatin remodeling

  15. Families of microRNAs Expressed in Clusters Regulate Cell Signaling in Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Luis Steven Servín-González

    2015-06-01

    Full Text Available Tumor cells have developed advantages to acquire hallmarks of cancer like apoptosis resistance, increased proliferation, migration, and invasion through cell signaling pathway misregulation. The sequential activation of genes in a pathway is regulated by miRNAs. Loss or gain of miRNA expression could activate or repress a particular cell axis. It is well known that aberrant miRNA expression is well recognized as an important step in the development of cancer. Individual miRNA expression is reported without considering that miRNAs are grouped in clusters and may have similar functions, such as the case of clusters with anti-oncomiRs (23b~27b~24-1, miR-29a~29b-1, miR-29b-2~29c, miR-99a~125b-2, miR-99b~125a, miR-100~125b-1, miR-199a-2~214, and miR-302s or oncomiRs activity (miR-1-1~133a-2, miR-1-2~133a-1, miR-133b~206, miR-17~92, miR-106a~363, miR183~96~182, miR-181a-1~181b-1, and miR-181a-2~181b-2, which regulated mitogen-activated protein kinases (MAPK, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K, NOTCH, proteasome-culling rings, and apoptosis cell signaling. In this work we point out the pathways regulated by families of miRNAs grouped in 20 clusters involved in cervical cancer. Reviewing how miRNA families expressed in cluster-regulated cell path signaling will increase the knowledge of cervical cancer progression, providing important information for therapeutic, diagnostic, and prognostic methodology design.

  16. Oncogenic intra-p53 family member interactions in human cancers

    Directory of Open Access Journals (Sweden)

    Maria eFerraiuolo

    2016-03-01

    Full Text Available The p53 gene family members p53, p73 and p63 display several isoforms derived from the presence of internal promoters and alternative splicing events. They are structural homologues but hold peculiar functional properties. p53, p73 and p63 are tumor suppressor genes that promote differentiation, senescence and apoptosis. p53, unlike p73 and p63, is frequently mutated in cancer often displaying oncogenic gain of function (GOF activities correlated with the induction of proliferation, invasion, chemoresistance and genomic instability in cancer cells. These oncogenic functions are promoted either by the aberrant transcriptional cooperation of mutant p53 (mutp53 with transcription cofactors (e.g., NF-Y, E2F1, Vitamin D Receptor (VDR, Ets-1, NF-kB and YAP or by the interaction with the p53 family members, p73 and p63, determining their functional inactivation. The instauration of these aberrant transcriptional networks leads to increased cell growth, low activation of DNA damage response pathways (DNA damage response (DDR, DNA double-strand breaks (DSBs response, enhanced invasion and high chemoresistance to different conventional chemotherapeutic treatments. Several studies have clearly shown that different cancers harboring mutant p53 proteins exhibit a poor prognosis when compared to those carrying wild type p53 (wt-p53 protein. The interference of mutantp53/p73 and/or mutantp53/p63 interactions, thereby restoring p53, p73 and p63 tumor suppression functions, could be among the potential therapeutic strategies for the treatment of mutant p53 human cancers.

  17. Quality of Life and Mortality of Long-Term Colorectal Cancer Survivors in the Seattle Colorectal Cancer Family Registry.

    Directory of Open Access Journals (Sweden)

    Scott V Adams

    Full Text Available Because most colorectal cancer patients survive beyond five years, understanding quality of life among these long-term survivors is essential to providing comprehensive survivor care. We sought to identify personal characteristics associated with reported quality of life in colorectal cancer survivors, and sub-groups of survivors potentially vulnerable to very low quality of life.We assessed quality of life using the Veterans RAND 12-item Health Survey within a population-based sample of 1,021 colorectal cancer survivors in the Seattle Colorectal Cancer Family Registry, approximately 5 years post-diagnosis. In this case-only study, mean physical component summary scores and mental component summary scores were examined with linear regression. To identify survivors with substantially reduced ability to complete daily tasks, logistic regression was used to estimate odds ratios for "very low" summary scores, defined as a score in the lowest decile of the reference US population. All cases were followed for vital status following QoL assessment, and mortality was analyzed with Cox proportional hazards regression.Lower mean physical component summary score was associated with older age, female sex, obesity, smoking, and diabetes or other co-morbidity; lower mean mental component summary score was associated with younger age and female sex. Higher odds of very low physical component summary score was associated with older age, obesity, less education, smoking, co-morbidities, and later stage at diagnosis; smoking was associated with higher odds of very low mental component summary score. A very low physical component score was associated with higher risk of mortality (hazard ratio (95% confidence interval: 3.97 (2.95-5.34.Our results suggest that identifiable sub-groups of survivors are vulnerable to very low physical components of quality of life, decrements that may represent meaningful impairment in completing everyday tasks and are associated with

  18. Expression of myc family oncoproteins in small-cell lung-cancer cell lines and xenografts

    DEFF Research Database (Denmark)

    Rygaard, K; Vindeløv, L L; Spang-Thomsen, M

    1993-01-01

    . WE examined the expression of myc proto-oncogenes at the mRNA and protein level in 23 cell lines or xenografts. In the cell lines, the doubling time and the cell-cycle distribution, as determined by flow-cytometric DNA analysis, were examined to establish whether the level of myc......A number of genes have altered activity in small-cell lung cancer (SCLC), but especially genes of the myc family (c-myc, L-myc and N-myc) are expressed at high levels in SCLC. Most studies have explored expression at the mRNA level, whereas studies of myc family oncoprotein expression are sparse......-gene-family expression correlated with proliferative parameters. All tumours expressed at least one myc family member at the mRNA level. Exclusive c-myc mRNA expression was demonstrated in 8 tumours, L-myc in 7 and N-myc in I. Five tumours expressed both c-myc and L-myc, and 2 tumours expressed both c-myc and N-myc...

  19. Cost-effectiveness of surveillance programs for families at high and moderate risk of hereditary non-polyposis colorectal cancer

    DEFF Research Database (Denmark)

    Rose Olsen, Kim; Bojesen, Stig E; Gerdes, Anne-Marie M;

    2007-01-01

    OBJECTIVES: Surveillance programs are recommended to both families at high risk (Amsterdam-positive families with known- and unknown mutation) and moderate risk (families not fulfilling all Amsterdam criteria) of colorectal cancer (CRC). Cost-effectiveness has so far only been estimated...... for the group at high risk. The aim of the present study is to determine cost-effectiveness of surveillance programs where families at both high and moderate risk of HNPCC participate. METHODS: A decision analytic model (Markov model) is developed to assess surveillance programs where families at high...... and moderate risk of HNPCC are offered surveillance from age 25 and age 45, respectively. The model includes costs for all families referred to genetic counseling, including genetic risk assessment, mutation analysis, and surveillance in relevant families with or without known mutation, plus the costs related...

  20. The influence of family history of cancer, irradiation and anticancer medication (mitomycin C), on the occurrence of multiple primary neoplasms with breast cancer

    International Nuclear Information System (INIS)

    The influence of family history of cancer, radiation therapy and anticancer drug therapy (mitomycin C) on the occurrence of multiple primary neoplasms, following treatment of a first primary cancer of the breast, was analyzed by the person-year method in 1,359 patients, in Japan. During 14,371.8 person-years of observation, 111 multiple primary neoplasms including bilateral breast cancers were found in 109 patients. The incidence rate of multiple primary neoplasms were 0.00772 per person-year. The incidence in patients with a family history of cancer was 1.29 times greater than that in patients without such a family history, and the incidence in patients with a family history of breast cancer was about three times greater than that in those without it (p < 0.01). Radiation therapy raised the occurrence of subsequent primary neoplasms 1.28-fold (or 1.62 fold after 5 years), and mitomycin C (a total dose of 0.8 mg/kg) therapy caused no increase in the occurrence of subsequent primary cancers, after an observation of 10 years or so. (author)

  1. Breast cancer-specific intrusions are associated with increased cortisol responses to daily life stressors in healthy women without personal or family histories of breast cancer.

    Science.gov (United States)

    Dettenborn, Lucia; James, Gary D; Valdimarsdottir, Heiddis B; Montgomery, Guy H; Bovbjerg, Dana H

    2006-10-01

    Studies indicate that women fear breast cancer more than any other disease and that women's levels of breast cancer-specific intrusions are related to their perceived risk of breast cancer. Here, we explore possible biological consequences of higher breast cancer risk perceptions and intrusions in healthy women without personal or family histories of the disease. We hypothesized that women with higher perceived risk would have more intrusions about breast cancer, which would constitute a background stressor sufficient to increase hypothalamus-pituitary-adrenal axis (HPA) responsivity to daily stress. HPA responses to an ordinary life stressor (work) were assessed in 141 employed women (age = 37.2+/-9.2) without personal or family histories of breast cancer. Urinary cortisol excretion rates were assessed with timed sample collections at work, home, and during sleep. Repeated measures ANOVA revealed a significant Group by Time interaction with higher work cortisol levels in women with breast cancer-specific intrusions compared to women without intrusions (p cancer risk is associated with higher levels of breast cancer-specific intrusions that can result in increased cortisol responsivity to daily stressors. This heightened responsivity could have long-term negative health implications. PMID:16944305

  2. Hereditary/familial versus sporadic prostate cancer: few indisputable genetic differences and many similar clinicopathological features.

    Science.gov (United States)

    Alberti, C

    2010-01-01

    Genetic factors and their interactions with environmental conditions and internal microenvironment influence the prostate cancer (PC) development, so that gene expression couldn't strictly occur on the basis of reductionist determinisms of DNA causality but should also conform to multifactorial and stochastic events, moreover, considering the pre-RNA alternative splicing-mediated multi-protein assemblying mechanisms. Nevertheless, after age and ethnic background, the strongest epidemiological risk factor for PC is a positive family history. However, apart from RNaseL-, ElaC2-, MSR1-genes, there are not other identified high-risk genetic variants which might be considered responsible for hereditary PC, moreover suggesting that familial PC is a genetically heterogeneous disease, many gene loci rather than a specific major susceptibility gene predisposing to it. Gene-environment interactions play a crucial role in cancer development especially when low penetrance genes, such as in case of genetic polymorphisms, are the major players. Several epidemiological studies show, in some families, a possible, either syncronous or metachronous, association of other tumors (breast, brain, gastrointestinal tumors, lymphomas) with PC, thus suggesting a common genetic background. As far as the role of androgen metabolism and androgen receptor (AR)-related genes in the development of familial PC is concerned, a small number of either guanine-guanine-cytosine (risk. Regarding the expression of both androgen and estrogen receptor-related genes in sporadic and hereditary PC, the immunohistochemistry findings show that the percentage of AR-positive cancer cells is higher in hereditary PC than in sporadic forms, whereas the mean number of estrogen-alpha-receptor-positive stromal cells is higher in sporadic PC rather than in that hereditary. As for 5-alpha-steroid-reductase-2 gene, the dinucleotide thymine-adenine repeated 18 times on the last exon, confers an increased PC predisposition

  3. A meta-analysis of qualitative studies on living with oesophageal and clinically similar forms of cancer, seen from the perspective of patients and family members

    OpenAIRE

    Andreassen, Sissel; Randers, Ingrid; Ternulf Nyhlin, Kerstin; Mattiasson, Anne-Cathrine

    2010-01-01

    This study is part of a research programme of which the aim is to generate knowledge about patients' and family members' experiences of living with oesophageal cancer from their perspective. The aim of the present study was to extend this knowledge by adding other forms of cancer: other upper gastrointestinal cancer, and head and neck cancer. These cancer forms have clinical similarities with oesophageal cancer and the survival rates are similar. This study is a qualitative metaanalysis that ...

  4. Single nucleotide polymorphisms in the mitochondrial displacement loop and age-at-onset of familial breast cancer.

    Science.gov (United States)

    Lee, Haiping; Geng, Cuizhi; Cheng, Meng; Lee, Zheng; Guo, Zhanjun

    2016-09-01

    Single nucleotide polymorphisms (SNPs) are accumulated frequently in the mitochondrial displacement loop (D-loop) in various types of cancer, and their association with cancer risk and disease outcome has been extensively identified. We have identified specific risk-associated SNP for familial breast cancer patients previously. In this study, we investigated the association between age-at-onset and the SNPs in familial breast cancer patients. The SNP sites of nucleotides 16 311 T/C were identified for their association with age-at-onset using the log-rank test. The age-at-onset of the patients with the minor allele C genotype was significantly earlier than that of patients carrying the T genotype at the site 16 311 (p = 0.032). Accordingly, the genetic polymorphisms in the mitochondrial D-loop are predictive markers for age-at-onset in familial breast cancer patients, which may help to identify familial breast cancer patient subgroups at high risk of early onset. PMID:27158866

  5. Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival.

    Science.gov (United States)

    Syamala, Volga S; Sreeja, Leelakumari; Syamala, Vani; Raveendran, Praveenkumar B; Balakrishnan, Rajan; Kuttan, Ratheesan; Ankathil, Ravindran

    2008-01-01

    Identifying genes associated with familial inheritance of breast cancer continues to be a major goal of current research as the known high penetrance genes could be attributable for only a small percentage of the risk. So, it is hypothesized that the low penetrance genes may also modify the risk for familial breast cancer. In the present case-control study, undertaken to examine the influence of polymorphisms of GSTs in familial and sporadic breast cancer susceptibility, 597 women including 222 sporadic breast cancer patients, 125 familial breast cancer patients and 250 females with no history of cancer as controls were genotyped by PCR based methods. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were calculated by unconditional logistic regression adjusted to age. Interestingly, GSTM1 deletion was found to be significantly associated only with familial breast cancer (OR = 2.0; 95%CI = 1.252-3.128) while GSTT1 was associated only with sporadic breast cancer (OR = 2.3; 95%CI = 1.336-3.970). GSTP1 Ile105Val polymorphism was associated neither with sporadic nor familial breast cancer susceptibility (P value > 0.05). The GST genotypes did not have any effect on the survival of both familial and sporadic breast cancer patients. However, familial breast cancer patients with GSTM1 null genotype had a relative risk of 0.42 (95%CI = 0.18-0.97) for an advanced disease stage. The results indicate that, in addition to the known high penetrance genes, certain low penetrance genes may also play a role, in the familial inheritance of breast cancer. It is also noticed that all the polymorphisms associated with sporadic breast cancer are not associated with familial breast cancer. PMID:18080216

  6. Family medicine, 'La Herencia' and breast cancer; understanding the (dis)continuities of predictive genetics in Cuba.

    Science.gov (United States)

    Gibbon, Sahra

    2011-06-01

    Building on social science research examining the relationship between genetic knowledge, identity and the family this paper takes the cultural context of Cuba as a site for critical ethnographic engagement. The paper makes use of research working with a range of Cuban public and genetic professionals as part of a collaborative research project exploring the social and cultural context of health beliefs about breast cancer. It illuminates the contrasting ways in which genomic knowledge linked to an increased risk of breast cancer is perceived, communicated, and acted upon. It is argued that the particular meaning and significance of genetic risk linked to breast cancer in this context must be examined in relation to long standing institutional practices relating to public health care provision. The focus on 'the family' in the provision of Cuban health provides a particularly viable foundation for the expansion of what is described as 'community genetics', including the collation of family history details for common complex diseases such as breast cancer. Nevertheless specific public perceptions of risk related to breast cancer and the difficulties of discussing a diagnosis of cancer openly in the family point to the very specific challenges for the translation and application of predictive interventions in Cuba. In summary the dynamic interrelationship between public health, perceptions of risk or health beliefs about the causes of the disease and attitudes towards cancer diagnosis within the family point to both continuities and discontinuities in the way that genomic interventions linked to breast cancer are unfolding as part of a dynamic yet still ostensibly socialist project of health care in Cuba.

  7. Striving to be prepared for the painful: Management strategies following a family member's diagnosis of advanced cancer

    Directory of Open Access Journals (Sweden)

    Hedberg Berith

    2011-10-01

    Full Text Available Abstract Background Cancer has consequences not only for the sick person but also for those who have a close relationship with that person. Greater knowledge about how family members manage the situation in the period immediately following the diagnosis means greater opportunity to provide the best possible support for the family. The purpose of this study was to explore management strategies that family members use when the patient is in the early stage of treatment for advanced cancer. Methods Twenty family members of cancer patients were included in the study shortly after the diagnosis. The patients had been diagnosed 8-14 weeks earlier with advanced lung cancer or gastrointestinal cancer. The data were collected in interviews with family members and subjected to qualitative latent content analysis. Through the identification of similarities and dissimilarities in the units of meaning, abstraction into codes and sub-themes became possible. The sub-themes were then brought together in one overarching theme. Results The overall function of management strategies is expressed in the theme Striving to be prepared for the painful. The family members prepare themselves mentally for the anticipated tragedy. Family relationships become increasingly important, and family members want to spend all their time together. They try to banish thoughts of the impending death and want to live as normal a life as possible. It becomes important to family members to live in the present and save their energy for the time when they will need it the most. How participants handle their worries, anxiety and sadness can be categorized into seven sub-themes or management strategies: Making things easier in everyday life, Banishing thoughts about the approaching loss, Living in the present, Adjusting to the sick person's situation, Distracting oneself by being with others, Shielding the family from grief, and Attempting to maintain hope. Conclusions The findings revealed

  8. Differential Roles for DUSP Family Members in Epithelial-to-Mesenchymal Transition and Cancer Stem Cell Regulation in Breast Cancer.

    Science.gov (United States)

    Boulding, Tara; Wu, Fan; McCuaig, Robert; Dunn, Jennifer; Sutton, Christopher R; Hardy, Kristine; Tu, Wenjuan; Bullman, Amanda; Yip, Desmond; Dahlstrom, Jane E; Rao, Sudha

    2016-01-01

    Dual-specificity phosphatases (DUSPs) dephosphorylate threonine/serine and tyrosine residues on their substrates. Here we show that DUSP1, DUSP4, and DUSP6 are involved in epithelial-to-mesenchymal transition (EMT) and breast cancer stem cell (CSC) regulation. DUSP1, DUSP4, and DUSP6 are induced during EMT in a PKC pathway signal-mediated EMT model. We show for the first time that the key chromatin-associated kinase PKC-θ directly regulates a subset of DUSP family members. DUSP1, DUSP4, and DUSP6 globally but differentially co-exist with enhancer and permissive active histone post-translational modifications, suggesting that they play distinct roles in gene regulation in EMT/CSCs. We show that nuclear DUSP4 associates with the key acetyltransferase p300 in the context of the chromatin template and dynamically regulates the interplay between two key phosphorylation marks: the 1834 (active) and 89 (inhibitory) residues central to p300's acetyltransferase activity. Furthermore, knockdown with small-interfering RNAs (siRNAs) shows that DUSP4 is required for maintaining H3K27ac, a mark mediated by p300. DUSP1, DUSP4, and DUSP6 knockdown with siRNAs shows that they participate in the formation of CD44hi/CD24lo/EpCAM+ breast CSCs: DUSP1 knockdown reduces CSC formation, while DUSP4 and DUSP6 knockdown enhance CSC formation. Moreover, DUSP6 is overexpressed in patient-derived HER2+ breast carcinomas compared to benign mammary tissue. Taken together, these findings illustrate novel pleiotropic roles for DUSP family members in EMT and CSC regulation in breast cancer. PMID:26859151

  9. Differential Roles for DUSP Family Members in Epithelial-to-Mesenchymal Transition and Cancer Stem Cell Regulation in Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Tara Boulding

    Full Text Available Dual-specificity phosphatases (DUSPs dephosphorylate threonine/serine and tyrosine residues on their substrates. Here we show that DUSP1, DUSP4, and DUSP6 are involved in epithelial-to-mesenchymal transition (EMT and breast cancer stem cell (CSC regulation. DUSP1, DUSP4, and DUSP6 are induced during EMT in a PKC pathway signal-mediated EMT model. We show for the first time that the key chromatin-associated kinase PKC-θ directly regulates a subset of DUSP family members. DUSP1, DUSP4, and DUSP6 globally but differentially co-exist with enhancer and permissive active histone post-translational modifications, suggesting that they play distinct roles in gene regulation in EMT/CSCs. We show that nuclear DUSP4 associates with the key acetyltransferase p300 in the context of the chromatin template and dynamically regulates the interplay between two key phosphorylation marks: the 1834 (active and 89 (inhibitory residues central to p300's acetyltransferase activity. Furthermore, knockdown with small-interfering RNAs (siRNAs shows that DUSP4 is required for maintaining H3K27ac, a mark mediated by p300. DUSP1, DUSP4, and DUSP6 knockdown with siRNAs shows that they participate in the formation of CD44hi/CD24lo/EpCAM+ breast CSCs: DUSP1 knockdown reduces CSC formation, while DUSP4 and DUSP6 knockdown enhance CSC formation. Moreover, DUSP6 is overexpressed in patient-derived HER2+ breast carcinomas compared to benign mammary tissue. Taken together, these findings illustrate novel pleiotropic roles for DUSP family members in EMT and CSC regulation in breast cancer.

  10. Cancer Research Repository for Individuals With Cancer Diagnosis and High Risk Individuals.

    Science.gov (United States)

    2014-12-12

    Pancreatic Cancer; Thyroid Cancer; Lung Cancer; Esophageal Cancer; Thymus Cancer; Colon Cancer; Rectal Cancer; GIST; Anal Cancer; Bile Duct Cancer; Duodenal Cancer; Gallbladder Cancer; Gastric Cancer; Liver Cancer; Small Intestine Cancer; Peritoneal Surface Malignancies; Familial Adenomatous Polyposis; Lynch Syndrome; Bladder Cancer; Kidney Cancer; Penile Cancer; Prostate Cancer; Testicular Cancer; Ureter Cancer; Urethral Cancer; Hypopharyngeal Cancer; Laryngeal Cancer; Lip Cancer; Oral Cavity Cancer; Nasopharyngeal Cancer; Oropharyngeal Cancer; Paranasal Sinus Cancer; Nasal Cavity Cancer; Salivary Gland Cancer; Skin Cancer; CNS Tumor; CNS Cancer; Mesothelioma

  11. CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families

    Directory of Open Access Journals (Sweden)

    Jamile Abud

    2012-12-01

    Full Text Available CONTEXT: CHEK2 encodes a cell cycle checkpoint kinase that plays an important role in the DNA damage repair pathway, activated mainly by ATM (Ataxia Telangiectasia Mutated in response to double-stranded DNA breaks. A germline mutation in CHEK2, 1100delC, has been described as a low penetrance allele in a significant number of families with breast and colorectal cancer in certain countries and is also associated with increased risk of contralateral breast cancer in women previously affected by the disease. About 5%-10% of all breast and colorectal cancers are associated with hereditary predisposition and its recognition is of great importance for genetic counseling and cancer risk management. OBJECTIVES: Here, we have assessed the frequency of the CHEK2 1100delC mutation in the germline of 59 unrelated Brazilian individuals with clinical criteria for the hereditary breast and colorectal cancer syndrome. METHODS: A long-range PCR strategy followed by gene sequencing was used. RESULTS: The 1100delC mutation was encountered in the germline of one (1.7% individual in this high risk cohort. This indicates that the CHEK2 1100delC is not commonly encountered in Brazilian families with multiple diagnoses of breast and colorectal cancer. CONCLUSION: These results should be confirmed in a larger series of families and further testing should be undertaken to investigate the molecular mechanisms underlying the hereditary breast and colorectal cancer phenotype.

  12. Germline SFTPA1 mutation in familial idiopathic interstitial pneumonia and lung cancer.

    Science.gov (United States)

    Nathan, Nadia; Giraud, Violaine; Picard, Clément; Nunes, Hilario; Dastot-Le Moal, Florence; Copin, Bruno; Galeron, Laurie; De Ligniville, Alice; Kuziner, Nathalie; Reynaud-Gaubert, Martine; Valeyre, Dominique; Couderc, Louis-Jean; Chinet, Thierry; Borie, Raphaël; Crestani, Bruno; Simansour, Maud; Nau, Valérie; Tissier, Sylvie; Duquesnoy, Philippe; Mansour-Hendili, Lamisse; Legendre, Marie; Kannengiesser, Caroline; Coulomb-L'Hermine, Aurore; Gouya, Laurent; Amselem, Serge; Clement, Annick

    2016-04-15

    Idiopathic interstitial pneumonias (IIPs) comprise a heterogeneous group of rare lung parenchyma disorders with high morbidity and mortality, which can occur at all ages. In adults, the most common form of IIPs, idiopathic pulmonary fibrosis (IPF), has been associated with an increased frequency of lung cancer. The molecular basis of IIPs remains unknown in most cases. This study investigates IIP pathophysiology in 12 families affected by IPF and lung cancer. We identified, in a multigenerational family, nine members carrying a heterozygous missense mutation with evidence of pathogenicity inSFTPA1that encodes the surfactant protein (SP)-A1. The mutation (p.Trp211Arg), which segregates with a disease phenotype characterized by either isolated IIP/IPF, or IPF associated with lung adenocarcinoma, is located in the carbohydrate recognition domain (CRD) of SP-A1 and involves a residue invariant throughout evolution, not only in SP-A1, but also in its close paralog SP-A2 and other CRD-containing proteins. As shown through functional studies, the p.Trp211Arg mutation impairs SP-A1 secretion. Immunohistochemistry studies on patient alveolar epithelium showed an altered SP-A expression pattern. Overall, this first report of a germline molecular defect inSFTPA1unveils the key role of SP-A1 in the occurrence of several chronic respiratory diseases, ranging from severe respiratory insufficiency occurring early in life to the association of lung fibrosis and cancer in adult patients. These data also clearly show that, in spite of their structural and functional similarities, SP-A1 and SP-A2 are not redundant. PMID:26792177

  13. Expression of activator protein-1 (AP-1) family members in breast cancer

    International Nuclear Information System (INIS)

    The activator protein-1 (AP-1) transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer. We studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Expression levels of Ubiquitin C (UBC) were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student’s t-test, one-way ANOVA, logistic regression and Pearson’s correlation coefficient for statistical analyses. We found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues (p < 0.001), whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues (p < 0.001). In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative (p = 0.012) and PR negative (p = 0.037). Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas (p = 0.01). Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer

  14. Low penetrance alleles as risk modifiers in familial and sporadic breast cancer.

    Science.gov (United States)

    Esteban Cardeñosa, Eva; de Juan Jiménez, Inmaculada; Palanca Suela, Sarai; Chirivella González, Isabel; Segura Huerta, Angel; Santaballa Beltran, Ana; Casals El Busto, María; Barragán González, Eva; Fuster Lluch, Oscar; Bermúdez Edo, José; Bolufer Gilabert, Pascual

    2012-12-01

    The aim of the study is to investigate the relevance of rs1056663 and rs2708861 HUS1 polymorphisms, and rs104548, rs2981582 and rs2910164 polymorphisms of CASP8, FGFR2 and micro RNA 146A genes, respectively, as risk modifiers in hereditary breast or ovarian cancer (BC/OC) and risk factors in sporadic BC. We performed a case-control study in 189 healthy controls (CG) and 538 BC/OC cases, 340 with familial history of BC/OC (130 carriers of BRCA1/2 mutations and 210 non-carriers) and 198 sporadic BC/OC. The polymorphisms were assessed by real-time PCR using primers and fluorescent-labelled hybridization probes. We found statistically significant differences between familial BC/OC and CG for rs1056663 and rs2708861 HSU1 polymorphisms and rs2981582 FGFR2 polymorphism, particularly in non-carriers of BRCA1/2 mutations. In this group we found statistical differences for rs1056663 HSU1 and rs2981582 FGFR2 polymorphisms (p-trend risk of cancer (OR = 1.87; 95 % CI 1.19, 2.92). Furthermore, we found that the presence of rs1056663 and rs2708861 HUS1 polymorphisms is associated with early age of presentation of BC (p = 0.015) in the group of non-carriers of BRCA1/2 mutations. In addition, no association of the polymorphisms studied in sporadic BC was observed. In conclusion, the HUS1 and FGFR2 polymorphisms act as risk BC modifiers in familial BC/OC, particularly in the group of non-carriers of BRCA1/2 mutations. PMID:22926736

  15. Hypoxia-induced modulation of apoptosis and BCL-2 family proteins in different cancer cell types.

    Directory of Open Access Journals (Sweden)

    Audrey Sermeus

    Full Text Available Hypoxia plays an important role in the resistance of tumour cells to chemotherapy. However, the exact mechanisms underlying this process are not well understood. Moreover, according to the cell lines, hypoxia differently influences cell death. The study of the effects of hypoxia on the apoptosis induced by 5 chemotherapeutic drugs in 7 cancer cell types showed that hypoxia generally inhibited the drug-induced apoptosis. In most cases, the effect of hypoxia was the same for all the drugs in one cell type. The expression profile of 93 genes involved in apoptosis as well as the protein level of BCL-2 family proteins were then investigated. In HepG2 cells that are strongly protected against cell death by hypoxia, hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2 family proteins while none of them are decreased in A549 cells that are not protected against cell death by hypoxia. In HepG2 cells, hypoxia decreased NOXA and BAD abundance and modified the electrophoretic mobility of BIM(EL. BIM and NOXA are important mediators of etoposide-induced cell death in HepG2 cells and the hypoxia-induced modification of these proteins abundance or post-translational modifications partly account for chemoresistance. Finally, the modulation of the abundance and/or of the post-translational modifications of most proteins of the BCL-2 family by hypoxia involves p53-dependent and -independent pathways and is cell type-dependent. A better understanding of these cell-to-cell variations is crucial in order to overcome hypoxia-induced resistance and to ameliorate cancer therapy.

  16. Early detection of ovarian cancer in FB&H - role of family medicine team

    Directory of Open Access Journals (Sweden)

    Dž. Ljuca

    2007-08-01

    Full Text Available Assessment of problems with ovarian malignancy in the Federation B&H requires a comprehensive and precise analysis of the population characteristics with particular focus on risk factors such as age, parity, hereditary factors, menstrual cycle characteristics (short cycle, early menarche, late menopause. A retrospective study of medical documentation involving 272 patients with ovarian cancer within the Federation of BiH in the period from 1996 to 2000 was conducted. Usual statistical methods were used (T- test, 2 -Test, Fisher exact test. The research showed that the disease was in most cases diagnosed too late, in the stages III and IV (60% whereas histology of the tissue showed epithelial cancer in 88,6% cases, most frequently between the age of 55 to 70. Out of 272 patients null-parity was recorded in 16,9 %, whereas 19,8 % of patients had just one pregnancy. Menstrual cycle duration shorter than 21 days was recorded in 26,5% cases. Approximately 1,8% patients had close relatives that suffered of cancer of breast, ovary or colon. Prerequisites for application of algorhithms in diagnostic procedures would be met by identification of risk groups consisting of those with one or more risk factors in their history. Bearing in mind the role of the family doctors in the future health system reform, it can be concluded that they could have an important role in the process.

  17. Experiences and perceived needs of children and teenagers with cancer and their families

    Directory of Open Access Journals (Sweden)

    Pilar González Carrión

    2005-06-01

    Full Text Available Purpose:- To know the experiencies and perceived needs of children and teenagers with cancer and their care givers regarding the received care and their oncological process. - To identify proposals for improving care.Methodology: A qualitative study based on individual semistructured interviews and focus interviews with children and teenagers diagnosed of cancer was designed. Results: Hospitalization, therapeutic and diagnose procedures, side effects and isolation when neutropenia, were identified as the main traumatic experiencies suffered by children and relatives. These issues were related to physic, psycologic, social and educational problems. Mothers showed sad and other depression feelings, although those feelings changed as the process of the illness evolved. Some improvement proposals were made by relatives, including the need of a better correlation between health resources and patient/relatives needs. The proffesional support and the care received were given great value.Conclusions: The illness was associated to physic, psycologic and social consequencies for both patients and relatives. Taking their opinion into account is very useful to improve the quality of the health servicies offered to children with cancer and their family.

  18. Trefoil factor family (TFF) proteins as potential serum biomarkers in patients with metastatic colorectal cancer.

    Science.gov (United States)

    Vocka, M; Langer, D; Petrtyl, J; Vockova, P; Hanus, T; Kalousova, M; Zima, T; Petruzelka, L

    2015-01-01

    Trefoil factor family (TFF) is composed of three secretory proteins (TFF1, TFF2 and TFF3) that play an important role in mucosal protection of gastrointestinal tract. Their overexpression in colorectal tumors seems to be associated with more aggressive disease. We collected serum samples from 79 healthy controls and 97 patients with metastatic colorectal cancer at the time of diagnosis or at progression. Serum levels of TTF1-3, CEA and CA19-9 were measured by ELISA. Serum TFF1 and TFF3 levels were significantly higher in patients with colorectal cancer compared to healthy controls (p TFF3 correlated with extent of liver involvement in patient without pulmonary metastases and patients with higher TFF3 levels had significantly worse outcome (p TFF3 had higher sensitivity and the same specificity. Our results indicate that TFF3 is an effective biomarker in patients with metastatic colorectal cancer with higher sensitivity than CEA a CA19-9. TFF3 levels strongly correlate with extension of liver disease and seem to have prognostic value.

  19. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

    2015-11-01

    Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells. PMID:26058357

  20. The Caregiving Experience in a Racially Diverse Sample of Cancer Family Caregivers

    Science.gov (United States)

    Siefert, Mary Lou; Williams, Anna-leila; Dowd, Michael F.; Chappel-Aiken, Lolita; McCorkle, Ruth

    2009-01-01

    The literature supports a variety of predictor variables to account for the psychological and stress burden experienced by cancer family caregivers. Missing among the predictor variables are the differences by or influence of race/ethnicity. The purpose of this study was to describe the sample, explore differences in outcomes by patient and family caregiver characteristics, and determine if any of the patient and family characteristics, including race/ethnicity, predicted outcomes. Cross-sectional surveys were used to determine sociodemographics, psychological and physical health, and burdens of caregiving among 54 caregivers. The analysis consisted of descriptive methods, including frequencies and t tests, and regression modeling. The sample was 35% African American or Hispanic. African American and Hispanic caregivers were younger than white caregivers and more often women, were rarely the spouse of the patient, and frequently had other dependents, including children and older parents. African American and Hispanic caregivers reported lower incomes and more burden related to finances and employment than did white caregivers. When controlling for sociodemographic factors, there was no difference by race/ethnicity on the outcome measures. The experience of caregiving may supersede race/ethnicity and may be its own cultural entity. Areas of concern include the interrelationship between socioeconomic status and race/ethnicity, the absence of cultural frameworks to direct caregiver research, and the question of cultural relevance of measurement tools. PMID:18772665

  1. Protecting Family Interests: An Interview Study with Foreign-Born Parents Struggling On in Childhood Cancer Care

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    Pernilla Pergert

    2012-01-01

    Full Text Available Sweden's population is gradually changing to become more multiethnic and diverse and that applies also for recipients of health care, including childhood cancer care. A holistic view on the sick child in the context of its family has always been a cornerstone in childhood cancer care in Sweden. The purpose of this study was to gain knowledge about the experiences and main concern of foreign-born parents in the context of paediatric cancer care. Interviews were performed with eleven foreign-born parents and data were analysed using a classic grounded theory approach. Foreign-born parents often feel in a position of powerless dependence, but family interests are protected in their approaches to interaction with healthcare staff, through cooperation, contesting, and reluctant resigning. Healthcare staff need to listen to foreign-born parents and deal with their concerns seriously to prevent powerless-dependence and work for trustful cooperation in the common fight against childhood cancer.

  2. Effect of Family History on Outcomes in Patients Treated With Definitive Brachytherapy for Clinically Localized Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: To determine the impact familial prostate cancer has on prognosis in men treated with brachytherapy for clinically localized prostate cancer. Methods and Materials: A total of 1,738 consecutive patients with prostate cancer (cT1-3, N0/X, M0) received low-dose-rate brachytherapy alone or in combination with external beam radiation therapy or hormone ablation from 1992 to 2005. The primary end-point was freedom from biochemical failure (FFBF) using the Phoenix definition. Minimum follow-up was 2 years and the median follow-up was 60 months (range, 24-197 months). Results: A total of 187 of 1,738 men (11%) had a family history of prostate cancer in a first-degree relative. For the low-risk patients, both groups had similar actuarial 5-year FFBF (97.2% vs. 95.5%, p = 0.516). For intermediate-risk patients, there was a trend toward improved biochemical control in men positive for family history (5-yr FFBF 100% vs. 93.6%, p = 0.076). For the high-risk patients, men with a positive family history had similar 5-year FFBF (92.8% vs. 85.2%, p = 0.124). On multivariate analysis, family history was not significant; use of hormones, high biologic effective dose, initial prostate-specific antigen value, and Gleason score were the significant variables predicting biochemical control. Conclusions: This is the first study to examine the relationship of familial prostate cancer and outcomed in men treated with brachytherapy alone or in combination therapy. Men with a positive family history have clinicopathologic characteristics and biochemical outcomes similar to those with sporadic disease

  3. Low incidence of germline mutation in BRCA1 Exon 11 among early-onset and familial Filipino breast cancer patients

    International Nuclear Information System (INIS)

    Breast cancer susceptibility gene, type 1 (BRCA1) has been thought to be responsible for about 45% of families with multiple breast carcinoma cases and for more than 80% of hereditary breast and ovarian cancer (HBOC) families. About 61-75% of the reported distinct alterations that result in truncated protein products have been found in exon 11 which comprises 61% (3427bp) of the coding sequence of BRCA1(5592bp). Protein truncation test (PTT) has become a popular method as an efficient means of screening mutations in a coding sequence that lead to a truncated protein product. In this study, 34 early-onset and/or familial breast cancer (FBC) patients were investigated. Twenty-six patients are early-onset B(o)C cases (diagnosed≤40 years old), 14 of which have familiality of the disease. Among the 8 patients that have been diagnosed above 40 years old, 7 have familial clustering. Through radioactive PTT analysis of the 34 BC cases in a 5-20% denaturing gradient polyacrylamide gel, we found only one mutation in exon 11 having a 29.7 kDa truncated protein product. Our results corroborate the findings of a recently reported study of unselected incident breast cancer cases in the Philippines where the prevalence of BRCA1 mutation is also low. This would, however, be the second documented mutation in BRCA1 exon 11 in a Filipino BC patient since 1998. (author)

  4. Family medicine, ‘La Herencia’ and breast cancer; understanding the (dis)continuities of predictive genetics in Cuba

    Science.gov (United States)

    Gibbon, Sahra

    2011-01-01

    Building on social science research examining the relationship between genetic knowledge, identity and the family this paper takes the cultural context of Cuba as a site for critical ethnographic engagement. The paper makes use of research working with a range of Cuban publics and genetic professionals as part of a collaborative research project exploring the social and cultural context of health beliefs about breast cancer. It illuminates the contrasting ways in which genomic knowledge linked to an increased risk of breast cancer is perceived, communicated, and acted upon. It is argued that the particular meaning and significance of genetic risk linked to breast cancer in this context must be examined in relation to long standing institutional practices relating to public health care provision. The focus on ‘the family’ in the provision of Cuban health provides a particularly viable foundation for the expansion of what is described as ‘community genetics’, including the collation of family history details for common complex diseases such as breast cancer. Nevertheless specific public perceptions of risk related to breast cancer and the difficulties of discussing a diagnosis of cancer openly in the family point to the very specific challenges for the translation and application of predictive interventions in Cuba. In summary the dynamic interrelationship between public health, perceptions of risk or health beliefs about the causes of the disease and attitudes towards cancer diagnosis within the family point to both continuities and discontinuities in the way that genomic interventions linked to breast cancer are unfolding as part of a dynamic yet still ostensibly socialist project of health care in Cuba. PMID:21239101

  5. Odin (ANKS1A is a Src family kinase target in colorectal cancer cells

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    Feller Stephan M

    2008-10-01

    Full Text Available Abstract Background Src family kinases (SFK are implicated in the development of some colorectal cancers (CRC. One SFK member, Lck, is not detectable in normal colonic epithelium, but becomes aberrantly expressed in a subset of CRCs. Although SFK have been extensively studied in fibroblasts and different types of immune cells, their physical and functional targets in many epithelial cancers remain poorly characterised. Results 64 CRC cell lines were tested for expression of Lck. SW620 CRC cells, which express high levels of Lck and also contain high basal levels of tyrosine phosphorylated (pY proteins, were then analysed to identify novel SFK targets. Since SH2 domains of SFK are known to often bind substrates after phosphorylation by the kinase domain, the LckSH2 was compared with 14 other SH2s for suitability as affinity chromatography reagent. Mass spectrometric analyses of LckSH2-purified pY proteins subsequently identified several proteins readily known as SFK kinase substrates, including cortactin, Tom1L1 (SRCASM, GIT1, vimentin and AFAP1L2 (XB130. Additional proteins previously reported as substrates of other tyrosine kinase were also detected, including the EGF and PDGF receptor target Odin. Odin was further analysed and found to contain substantially less pY upon inhibition of SFK activity in SW620 cells, indicating that it is a formerly unknown SFK target in CRC cells. Conclusion Rapid identification of known and novel SFK targets in CRC cells is feasible with SH2 domain affinity chromatography. The elucidation of new SFK targets like Odin in epithelial cancer cells is expected to lead to novel insight into cancer cell signalling mechanisms and may also serve to indicate new biomarkers for monitoring tumor cell responses to drug treatments.

  6. Association of common ATM variants with familial breast cancer in a South American population

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    Peralta Octavio

    2008-04-01

    Full Text Available Abstract Background The ATM gene has been frequently involved in hereditary breast cancer as a low-penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory. Methods In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G>A missense variant and the IVS38-8T>C and the IVS24-9delT polymorphisms. Results In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T>C, or 5557G>A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T>C (OR = 3.09 [95%CI 1.11–8.59], p = 0.024. The IVS24-9 T/(-T, IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [95%CI 1.16–8.89], p = 0.021. The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1. We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population. Conclusion The IVS24-9 T/(-T, IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic inestability or by altering the effect of the normal DNA damage response.

  7. Association of common ATM variants with familial breast cancer in a South American population

    International Nuclear Information System (INIS)

    The ATM gene has been frequently involved in hereditary breast cancer as a low-penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory. In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G>A missense variant and the IVS38-8T>C and the IVS24-9delT polymorphisms. In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T>C, or 5557G>A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T>C (OR = 3.09 [95%CI 1.11–8.59], p = 0.024). The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [95%CI 1.16–8.89], p = 0.021). The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1). We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population. The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic inestability or by altering the effect of the normal DNA damage response

  8. The psychological impact of mammographic screening on women with a family history of breast cancer--a systematic review.

    Science.gov (United States)

    Watson, Eila K; Henderson, Bethan J; Brett, Joanne; Bankhead, Clare; Austoker, Joan

    2005-11-01

    This systematic review aims to assess the psychological impact of mammographic screening on women with a family history of breast cancer. Women with a family history, and hence increased risk, of breast cancer are known to experience higher levels of anxiety about cancer. They are also often offered screening from an earlier age. The psychological consequences of screening are therefore of particular importance for this group of women. A comprehensive search of 4 electronic databases was conducted from 1982 to 2003, combining sets of terms relating to (1) breast screening or mammography (breast screen*; mammogra*), (2) psychological impact (adverse effects; anxi*; distress; nervous; psych*, psychological consequences; stress; worry) and (3) family history. Reference lists from relevant papers were examined for additional papers. The review identified seven papers from four countries. Overall, the findings indicate that, similar to women in the general population, most women with a family history do not appear to experience high levels of anxiety associated with mammographic screening. Although women who are recalled for further tests do experience increased anxiety the levels appear to be no greater than for women without a family history. We conclude that further research on this topic is required--this should include studies designed specifically to consider both the negative and positive impact of mammographic screening on women with a family history, using validated measures of anxiety and worry in combination with qualitative research.

  9. MiRNA Profiles in Lymphoblastoid Cell Lines of Finnish Prostate Cancer Families.

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    Daniel Fischer

    Full Text Available Heritable factors are evidently involved in prostate cancer (PrCa carcinogenesis, but currently, genetic markers are not routinely used in screening or diagnostics of the disease. More precise information is needed for making treatment decisions to distinguish aggressive cases from indolent disease, for which heritable factors could be a useful tool. The genetic makeup of PrCa has only recently begun to be unravelled through large-scale genome-wide association studies (GWAS. The thus far identified Single Nucleotide Polymorphisms (SNPs explain, however, only a fraction of familial clustering. Moreover, the known risk SNPs are not associated with the clinical outcome of the disease, such as aggressive or metastasised disease, and therefore cannot be used to predict the prognosis. Annotating the SNPs with deep clinical data together with miRNA expression profiles can improve the understanding of the underlying mechanisms of different phenotypes of prostate cancer.In this study microRNA (miRNA profiles were studied as potential biomarkers to predict the disease outcome. The study subjects were from Finnish high risk prostate cancer families. To identify potential biomarkers we combined a novel non-parametrical test with an importance measure provided from a Random Forest classifier. This combination delivered a set of nine miRNAs that was able to separate cases from controls. The detected miRNA expression profiles could predict the development of the disease years before the actual PrCa diagnosis or detect the existence of other cancers in the studied individuals. Furthermore, using an expression Quantitative Trait Loci (eQTL analysis, regulatory SNPs for miRNA miR-483-3p that were also directly associated with PrCa were found.Based on our findings, we suggest that blood-based miRNA expression profiling can be used in the diagnosis and maybe even prognosis of the disease. In the future, miRNA profiling could possibly be used in targeted screening

  10. Health care restructuring and family physician care for those who died of cancer

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    Johnston Grace

    2005-01-01

    Full Text Available Abstract Background During the 1990s, health care restructuring in Nova Scotia resulted in downsized hospitals, reduced inpatient length of stay, capped physician incomes and restricted practice locations. Concurrently, the provincial homecare program was redeveloped and out-of-hospital cancer deaths increased from 20% (1992 to 30% (1998. These factors all pointed to a transfer of end-of-life inpatient hospital care to more community-based care. The purpose of this study was to describe the trends in the provision of Family Physician (FP visits to advanced cancer patients in Nova Scotia (NS during the years of health care restructuring. Methods Design Secondary multivariate analysis of linked population-based datafiles including the Queen Elizabeth II Health Sciences Centre Oncology Patient Information System (NS Cancer Registry, Vital Statistics, the NS Hospital Admissions/Separations file and the Medical Services Insurance Physician Services database. Setting Nova Scotia, an eastern Canadian province (population: 950,000. Subjects: All patients who died of lung, colorectal, breast or prostate cancer between April 1992 and March 1998 (N = 7,212. Outcome Measures Inpatient and ambulatory FP visits, ambulatory visits by location (office, home, long-term care facility, emergency department, time of day (regular hours, after hours, total length of inpatient hospital stay and number of hospital admissions during the last six months of life. Results In total, 139,641 visits were provided by family physicians: 15% of visits in the office, 10% in the home, 5% in the emergency department (ED, 5% in a long-term-care centre and 64% to hospital inpatients. There was no change in the rate of FP visits received for office, home and long-term care despite the fact that there were 13% fewer hospital admissions, and length of hospital stay declined by 21%. Age-sex adjusted estimates using negative binomial regression indicate a decline in hospital inpatient FP

  11. Role of KCNMA1 in breast cancer.

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    Martin Oeggerli

    Full Text Available KCNMA1 encodes the α-subunit of the large conductance, voltage and Ca(2+-activated (BK potassium channel and has been reported as a target gene of genomic amplification at 10q22 in prostate cancer. To investigate the prevalence of the amplification in other human cancers, the copy number of KCNMA1 was analyzed by fluorescence-in-situ-hybridization (FISH in 2,445 tumors across 118 different tumor types. Amplification of KCNMA1 was restricted to a small but distinct fraction of breast, ovarian and endometrial cancer with the highest prevalence in invasive ductal breast cancers and serous carcinoma of ovary and endometrium (3-7%. We performed an extensive analysis on breast cancer tissue microarrays (TMA of 1,200 tumors linked to prognosis. KCNMA1 amplification was significantly associated with high tumor stage, high grade, high tumor cell proliferation, and poor prognosis. Immunofluorescence revealed moderate or strong KCNMA1 protein expression in 8 out of 9 human breast cancers and in the breast cancer cell line MFM223. KCNMA1-function in breast cancer cell lines was confirmed by whole-cell patch clamp recordings and proliferation assays, using siRNA-knockdown, BK channel activators such as 17ß-estradiol and the BK-channel blocker paxilline. Our findings revealed that enhanced expression of KCNMA1 correlates with and contributes to high proliferation rate and malignancy of breast cancer.

  12. Histopathological features of breast tumours in BRCA1, BRCA2 and mutation-negative breast cancer families

    International Nuclear Information System (INIS)

    Histopathological features of BRCA1 and BRCA2 tumours have previously been characterised and compared with unselected breast tumours; however, familial non-BRCA1/2 tumours are less well known. The aim of this study was to characterise familial non-BRCA1/2 tumours and to evaluate routine immunohistochemical and pathological markers that could help us to further distinguish families carrying BRCA1/2 mutations from other breast cancer families. Breast cancer tissue specimens (n = 262) from 25 BRCA1, 20 BRCA2 and 74 non-BRCA1/2 families were studied on a tumour tissue microarray. Immunohistochemical staining of oestrogen receptor (ER), progesterone receptor (PgR) and p53 as well as the histology and grade of these three groups were compared with each other and with the respective information on 862 unselected control patients from the archives of the Pathology Department of Helsinki University Central Hospital. Immunohistochemical staining of erbB2 was also performed among familial cases. BRCA1-associated cancers were diagnosed younger and were more ER-negative and PgR-negative, p53-positive and of higher grade than the other tumours. However, in multivariate analysis the independent factors compared with non-BRCA1/2 tumours were age, grade and PgR negativity. BRCA2 cases did not have such distinctive features compared with non-BRCA1/2 tumours or with unselected control tumours. Familial cases without BRCA1/2 mutations had tumours of lower grade than the other groups. BRCA1 families differed from mutation-negative families by age, grade and PgR status, whereas ER status was not an independent marker

  13. Rapid Mutation Scanning of Genes Associated with Familial Cancer Syndromes Using Denaturing High-Performance Liquid Chromatography

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    Deborah J. Marsh

    2001-01-01

    Full Text Available Germline mutations in tumor suppressor genes, or less frequently oncogenes, have been identified in up to 19 familial cancer syndromes including Li-Fraumeni syndrome, familial paraganglioma, familial adenomatous polyposis coli and breast and ovarian cancers. Multiple genes have been associated with some syndromes as approximately 26 genes have been linked to the development of these familial cancers. With this increased knowledge of the molecular determinants of familial cancer comes an equal expectation for efficient genetic screening programs. We have trialled denaturing highperformance liquid chromatography (dHPLC as a tool for rapid germline mutation scanning of genes implicated in three familial cancer syndromes - Cowden syndrome (PTEN mutation, multiple endocrine neoplasia type 2 (RET mutation and von Hippel-Lindau disease (VHL mutation. Thirty-two mutations, including 21 in PTEN, 9 in RET plus a polymorphism, and 2 in VHL, were analyzed using the WAVE DNA fragment analysis system with 100% detection efficiency. In the case of the tumor suppressor gene PTEN, mutations were scattered along most of the gene. However, mutations in the RET proto-oncogene associated with multiple endocrine neoplasia type 2 were limited to specific clusters or “hot spots”. The use of GC-clamped primers to scan for mutations scattered along PTEN exons was shown to greatly enhance the sensitivity of detection of mutant hetero- and homoduplex peaks at a single denaturation temperature compared to fragments generated using non-GC-clamped primers. Thus, when scanning tumor suppressor genes for germline mutation using dHPLC, the incorporation of appropriate GCclamped primers will likely increase the efficiency of mutation detection.

  14. Familial prostate cancer has a more aggressive course than sporadic prostate cancer after treatment for localized disease, mainly due to a higher rate of distant metastases

    International Nuclear Information System (INIS)

    Purpose: We had already established that familial prostate cancer, defined as prostate cancer diagnosed in a father or brother, was an independent predictor of biochemical failure after treatment for localized disease. Our aim was to determine whether differences in outcome could be observed with respect to clinical failures (either local or distant) between the two forms of prostate cancer. Methods: Of the 1685 consecutive cases with localized prostate carcinoma treated between 1986 and 1996, patients with the following were excluded from the present study: no pretreatment Prostatic Specific Antigen (iPSA) level (n=54), no biopsy Gleason score (bGS) (n=25), adjuvant or neoadjuvant treatment (n=234), no available follow-up PSA level (n=30). We also excluded 617 patients who did not have a minimum of 3 years potential follow-up. The analysis was performed on 725 cases. Radiotherapy (RT) was the primary treatment in 330 patients and radical prostatectomy (RP) in 395 patients. Five percent had clinical stage T3 disease (n=37). Positive family history was defined as the presence of prostate cancer in a first degree relative (father or brother). The outcomes of interest were biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), local relapse-free survival (locRFS), distant relapse-free survival (dRFS). We used proportional hazards to analyze the effect of family history and other potential confounding variables (i.e. age, race, treatment modality, stage, biopsy GS, and iPSA levels) on treatment outcome. We included pathologic findings (extracapsular extension, seminal vesicle involvement, surgical margin involvement, and lymph node metastases) in a separate analysis for RP patients. Results: The median follow-up was 45 months. Eight percent of all cases (n=57) had a positive family history. The 5-year bRFS rates for patients with negative and positive family history were 54% and 38%, respectively (p<0.001). The 5-year cRFS rates for patients

  15. Gendered Processes in Hospice Palliative Home Care for Seniors With Cancer and Their Family Caregivers.

    Science.gov (United States)

    Sutherland, Nisha; Ward-Griffin, Catherine; McWilliam, Carol; Stajduhar, Kelli

    2016-06-01

    There has been limited investigation into the processes that shape gender (in)equities in hospice palliative home care. As part of a larger critical ethnographic study, we examined how and why gender relations occur in this context. Using a critical feminist lens, we conducted in-depth interviews with clients living with terminal cancer, their family caregivers and primary nurses; observations of agency home visits; and review of institutional documents. A gender-based analysis revealed that gender enactments of Regulating Gender Relations were legitimized through ideological processes of Normalizing Gender Relations and Equalizing Gender Relations (Re)produced through institutional discourses of individualism and egalitarianism, these gendered processes both advantaged and disadvantaged men and women in hospice palliative home care. Findings suggest that to promote equity, health care providers and policy makers must attend to gender as a prevalent social determinant of health and health care. Implications for policy, practice, education, and research are discussed. PMID:26489710

  16. Psychosocial Interventions for Families with Parental Cancer and Barriers and Facilitators to Implementation and Use – A Systematic Review

    Science.gov (United States)

    Inhestern, Laura; Haller, Anne-Catherine; Wlodarczyk, Olga; Bergelt, Corinna

    2016-01-01

    Background Parental cancer has a significant impact on minor children and families. Psychosocial interventions for affected families can provide support where necessary. This systematic review aims at providing an overview of existing interventions and support programs and focuses on the systematic investigation of barriers and facilitators for using psychosocial interventions for families affected by parental cancer (PROSPERO; registration number CRD42014013020). Methods A search of five electronic databases (EMBASE, MEDLINE, PsycInfo, Psyndex, CINAHL) was conducted in June 2014, and updated in September 2015. We included any kind of studies reporting psychosocial support services or interventions for families affected by parental cancer. Study quality was assessed using the Mixed Method Assessment Tool. Narrative synthesis and thematic analyses were undertaken to examine the included interventions and to identify barriers and facilitators for use and implementation. Results A total of 36 studies covering 19 interventions and support services were included in the systematic review. Interventions focused on children, parents or several family members and analyses revealed a broad picture of theoretical background and primary aims. Several studies focused on developmental or implementation phases or descriptions of interventions. Other included studies reported results of evaluations using qualitative and quantitative methods. Results suggest that interventions are helpful and that participants improved in various outcomes. The thematic analyses indicate that barriers for use of support services refer to aspects concerning the patients and families, such as practical difficulties, perceived need for support or fear of stigma. Cancer patients who understood the need and benefit of support services may have used them more often. Additionally, intervention characteristics such as a flexible structure and accessibility were important to reach families affected by

  17. Two different BRCA2 mutations found in a multigenerational family with a history of breast, prostate, and lung cancers

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    Caporale DA

    2014-06-01

    Full Text Available Diane A Caporale, Erica E SwensonDepartment of Biology, University of Wisconsin – Stevens Point, Stevens Point, WI, USAAbstract: Breast and lung cancer are two of the most common malignancies in the United States, causing approximately 40,000 and 160,000 deaths each year, respectively. Over 80% of hereditary breast cancer cases are due to mutations in two breast cancer predisposition genes, BRCA1 and BRCA2. These are tumor-suppressor genes associated with DNA repair. Since the discovery of these two genes in the mid-1990s, several other breast cancer predisposition genes have been identified, such as the CHEK2 gene encoding a regulator of BRCA1. Recently, studies have begun investigating the roles of BRCA1 and BRCA2 gene expression in lung cancer. We conducted a family-based case study that included a bloodline of Italian heritage with several cases of breast cancer and associated cancers (prostate and stomach through multiple generations and on a nonblood relative of Scottish/Irish descent who was consecutively diagnosed with breast and lung cancer. Cancer history and environmental risk factors were recorded for each family member. To investigate possible genetic risks, we screened for mutations in specific hypervariable regions of the BRCA1, BRCA2, and CHEK2 genes. DNA was extracted and isolated from the individuals' hair follicles and cheek cells. Polymerase chain reaction (PCR, allele-specific PCR, and DNA sequencing were performed to identify and verify the presence or absence of mutations in these regions. Genotypes of several family members were determined and carriers of mutations were identified. Here we report for the first time the occurrence of two different BRCA2 frameshift mutations within the same family. Specifically, three Italian family members were found to be carriers of the BRCA2-c.2808_2811delACAA (3036delACAA mutation, a 4-nucleotide deletion in exon 11, which is a truncated mutation that causes deleterious function of

  18. Examining parents' assessments of objective and subjective social status in families of children with cancer.

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    Elizabeth A Gage-Bouchard

    Full Text Available INTRODUCTION: Understanding the social determinants of child health is a prominent area of research. This paper examines the measurement of socioeconomic position in a sample of families of children with cancer. Socioeconomic position is difficult to measure in pediatric health research due to sensitivity of asking about finances when research is conducted in health care delivery settings, financial volatility associated with periods of pediatric illness, and difficulty recruiting fathers to research. METHODS: Caregivers of children with cancer (n=76 completed a questionnaire that included the MacArthur Scale of Subjective Social Status (SSS. SSS was measured using two 10-rung ladders with differing referent groups: the US and respondents' communities. Respondents placed themselves on each ladder by placing an X on the rung that represented their social position in relation to the two referent groups. Individuals' SSS ratings and discrepancies in SSS ratings within couples were examined, and associations with objective social status measures were evaluated using Pearson correlations or t-tests. RESULTS: Parents' placement on the US and community ladders was positively associated with their income, education, wealth, household savings, and household savings minus debt. On average, respondents placed themselves higher on the US ladder compared to the community ladder. There was an average intra-couple discrepancy of 1.25 rungs in partner's placements on the US ladder and a 1.56 rung difference for the community ladder. This intra-couple discrepancy was not associated with gender. DISCUSSION: Results offer insight into the use of subjective social status measures to capture a more holistic assessment of socioeconomic position and the measurement of socioeconomic position in two-parent families.

  19. MR-guided intervention in women with a family history of breast cancer

    International Nuclear Information System (INIS)

    Objective: A study was undertaken to assess the clinical value of magnetic resonance (MR) imaging-guided interventions in women with a family history, but no personal history of breast cancer. Methods and patients: Retrospective review was performed on 63 consecutive women who had a family history, but no personal history of breast cancer. A total of 97 lesions were referred for an MR-guided intervention. Standardized MR examinations (1.0 T, T1-weighted 3D FLASH, 0.15 mmol Gd-DTPA/kg body weight, prone position) were performed using a dedicated system which allows vacuum assisted breast biopsy or wire localization. Results: Histologic findings in 87 procedures revealed 9 (10%) invasive carcinomas, 12 (14%) ductal carcinomas in situ, 2 atypical ductal hyperplasias (2.5%) and 2 atypical lobular hyperplasias (2.5%). Sixty-two (71%) benign histologic results are verified by an MR-guided intervention, retrospective correlation of imaging and histology and by subsequent follow-up. In ten lesions the indication dropped since the enhancing lesion was no longer visible. Absent enhancement was confirmed by short-term re-imaging of the noncompressed breast and by follow-up. Conclusion: Malignancy was found in 24%, high-risk lesions in 5% of successfully performed MR-guided biopsy procedures. A 57% of MR-detected malignancies were ductal carcinoma in situ. In 10% of the lesions the intervention was not performed, since no enhancing lesion could be reproduced at the date of anticipated intervention. Such problems may be avoided if the initial MRI is performed in the appropriate phase of the menstrual cycle and without hormonal replacement therapy

  20. Dietary practices in households as risk factors for stomach cancer: a familial study in Poland.

    Science.gov (United States)

    Jedrychowski, W; Boeing, H; Popiela, T; Wahrendorf, J; Tobiasz-Adamczyk, B; Kulig, J

    1992-06-01

    In the framework of a nationwide case-control study of risk factors for stomach cancer, a household survey was conducted on those food habits at the family level which were considered relevant for stomach cancer. The practices of 741 case and 741 control households were compared and relative risks calculated by the unconditional maximum likelihood method. For each household, the person responsible for cooking completed the survey. Respondents to the household survey were 35% of the cases and 40% of the controls of the case-control study and otherwise other household members. Case households relied more frequently on their own gardens as a major source of vegetables and fruit, and they cooked their vegetables more often than control households. The vegetable and fruit consumption during the summer period per family member was significantly less in case households compared to control households. The difference in per capita vegetable and fruit consumption between case and control households persisted, but was considerably less pronounced when the consumption of the index person (case or control) was subtracted from the household consumption. The consumption of mainly wholemeal bread showed a relative risk (RR) of 0.18 (95% CI 0.07-0.44) compared with mainly white bread consumption, whereas frequent frying and stewing of meat was associated with an increased risk compared to boiling of meat (RR = 2.06, 95% CI 1.48-2.87). No association with risk was found for long-term refrigerator use or other storage modalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1467778

  1. The CHEK2*1100delC variant acts as a breast cancer risk modifier in non-BRCA1/BRCA2 multiple-case families

    NARCIS (Netherlands)

    Oldenburg, RA; Kroeze-Jansema, K; Kraan, J; Morreau, H; Klijn, JGM; Hoogerbrugge, N; Ligtenberg, MJL; van Asperen, CJ; Vasen, HFA; Meijers, C; Meijers-Heijboer, H; de Bock, TH; Cornelisse, CJ; Devilee, P

    2003-01-01

    The frame-shifting mutation 1100delC in the cell-cycle-checkpoint kinase 2 gene (CHEK2) has been reported to be associated with familial breast cancer in families in which mutations in BRCA1 and BRCA2 were excluded. To investigate the role of,this variant as a candidate breast cancer susceptibility

  2. Identification of BRCA1/2 founder mutations in Southern Chinese breast cancer patients using gene sequencing and high resolution DNA melting analysis.

    Directory of Open Access Journals (Sweden)

    Ava Kwong

    Full Text Available BACKGROUND: Ethnic variations in breast cancer epidemiology and genetics have necessitated investigation of the spectra of BRCA1 and BRCA2 mutations in different populations. Knowledge of BRCA mutations in Chinese populations is still largely unknown. We conducted a multi-center study to characterize the spectra of BRCA mutations in Chinese breast and ovarian cancer patients from Southern China. METHODOLOGY/PRINCIPAL FINDINGS: A total of 651 clinically high-risk breast and/or ovarian cancer patients were recruited from the Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2011. Comprehensive BRCA1 and BRCA2 mutation screening was performed using bi-directional sequencing of all coding exons of BRCA1 and BRCA2. Sequencing results were confirmed by in-house developed full high resolution DNA melting (HRM analysis. Among the 451 probands analyzed, 69 (15.3% deleterious BRCA mutations were identified, comprising 29 in BRCA1 and 40 in BRCA2. The four recurrent BRCA1 mutations (c.470_471delCT, c.3342_3345delAGAA, c.5406+1_5406+3delGTA and c.981_982delAT accounted for 34.5% (10/29 of all BRCA1 mutations in this cohort. The four recurrent BRCA2 mutations (c.2808_2811delACAA, c.3109C>T, c.7436_7805del370 and c.9097_9098insA accounted for 40% (16/40 of all BRCA2 mutations. Haplotype analysis was performed to confirm 1 BRCA1 and 3 BRCA2 mutations are putative founder mutations. Rapid HRM mutation screening for a panel of the founder mutations were developed and validated. CONCLUSION: In this study, our findings suggest that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Southern Chinese population. Knowing the spectrum and frequency of the founder mutations in this population will assist in the development of a cost-effective rapid screening assay, which in turn facilitates genetic counseling and testing for the purpose of cancer risk assessment.

  3. Epidermolytic palmoplantar keratoderma cosegregates with a keratin 9 mutation in a pedigree with breast and ovarian cancer.

    Science.gov (United States)

    Torchard, D; Blanchet-Bardon, C; Serova, O; Langbein, L; Narod, S; Janin, N; Goguel, A F; Bernheim, A; Franke, W W; Lenoir, G M

    1994-01-01

    Epidermolytic palmoplantar keratosis (EPPK) cosegregates with breast and ovarian cancers in a large French pedigree, raising the possibility that a single genetic mutation might cause these conditions and offering a potential lead to the identification of a hereditary breast/ovarian cancer gene. We have performed linkage analysis and show that the EPPK locus lies on the long arm of chromosome 17 near the type I keratin gene cluster and the proposed breast cancer gene (BRCA1). The type I keratin 9 gene has been partially sequenced in four affected individuals. A single base mutation within the rod domain of the protein cosegregates with EPPK in all affected individuals tested. Although inheritance of this mutation is likely responsible for EPPK, it is unlikely to be the cause of the breast and ovarian cancer.

  4. A Grounded Theory of Students' Long-Distance Coping With a Family Member's Cancer.

    Science.gov (United States)

    Basinger, Erin D; Wehrman, Erin C; Delaney, Amy L; McAninch, Kelly G

    2015-08-01

    In this study, we explore how family members cope with one source of stress-cancer diagnosis and treatment. We suggest that coping away from one's family is characterized by constraints that are not common to proximal coping. We conducted six focus groups with college students (N = 21) at a university in the United States to investigate their long-distance coping experiences and used grounded theory methods to develop a model of college students' long-distance coping. Negotiating the tension between being here (at school) and being there (at home) was central to their experiences. Participants described four manifestations of their negotiation between here and there (i.e., expressing/hiding emotion, longing to care for the patient there/avoiding responsibility here, feeling shock at degeneration there/escaping degeneration by being here, and lacking information from there) and three strategies they used to cope (i.e., being here and withdrawing, being here and doing school, and seeking/not seeking support). PMID:25794524

  5. Psychological factors associated with the intention to choose for risk-reducing mastectomy in family cancer clinic attendees

    NARCIS (Netherlands)

    van Driel, C M G; Oosterwijk, J C; Meijers-Heijboer, E J; van Asperen, C J; Zeijlmans van Emmichoven, I A; de Vries, J; Mourits, M J E; Henneman, L; Timmermans, D R M; de Bock, G H

    2016-01-01

    OBJECTIVES: Women seeking counseling because of familial breast cancer occurrence face difficult decisions, such as whether and when to opt for risk-reducing mastectomy (RRM) in case of BRCA1/2 mutation. Only limited research has been done to identify the psychological factors associated with the de

  6. Higher cytoplasmic and nuclear poly(ADP-ribose) polymerase expression in familial than in sporadic breast cancer

    NARCIS (Netherlands)

    Klauke, M.L.; Hoogerbrugge-van der Linden, N.; Budczies, J.; Bult, P.; Prinzler, J.; Radke, C.; Krieken, J.H. van; Dietel, M.; Denkert, C.; Muller, B.M.

    2012-01-01

    Poly(ADP-ribose) polymerase 1 (PARP) is a key element of the single-base excision pathway for repair of DNA single-strand breaks. To compare the cytoplasmic and nuclear poly(ADP-ribose) expression between familial (BRCA1, BRCA2, or non BRCA1/2) and sporadic breast cancer, we investigated 39 sporadic

  7. How much colonoscopy screening should be recommended to individuals with various degrees of family history of colorectal cancer?

    NARCIS (Netherlands)

    J.A. Wilschut (Janneke); E.W. Steyerberg (Ewout); M.E. van Leerdam (Monique); I. Lansdorp-Vogelaar (Iris); J.D.F. Habbema (Dik); M. van Ballegooijen (Marjolein)

    2011-01-01

    textabstractBACKGROUND: Individuals with a family history of colorectal cancer (CRC) are at increased risk for CRC. Current screening recommendations for these individuals are based on expert opinion. The authors investigated optimal screening strategies for individuals with various degrees of famil

  8. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.

    2014-11-11

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

  9. Distance caregiving a family member with cancer: A review of the literature on distance caregiving and recommendations for future research.

    Science.gov (United States)

    Douglas, Sara L; Mazanec, Polly; Lipson, Amy; Leuchtag, Mary

    2016-04-10

    Distance caregivers (DCGs) are a growing phenomenon in the United States Family members are struggling to provide care to loved ones with chronic illnesses such as cancer, from a distance. Unlike local caregiving research, distance caregiving research is limited and inconsistent definitions of distance make it difficult to compare studies. To date, DCGs have not been afforded the opportunities for educational and emotional support that local caregivers have received from the health care teams. Because they are not usually present at medical appointments, DCGs do not receive first-hand information from the health care team about the patient's condition, disease progression, and/or treatment options. These caregivers report feeling left out of important family discussions. They experience anxiety related to the uncertainty of the family members' well-being and guilt related to not being available to help local caregivers more. The challenges of distance caregiving are especially evident when the distance caregiver has a parent with advanced cancer. Family-centered care, attending to the needs of the whole family regardless of their geographic location is critical for quality cancer care. In this manuscript, the sparse literature on distance caregiving is reviewed. Recommendations for future research and for the development of creative technologically advanced interventions for this underserved caregiving population are suggested.

  10. Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry

    International Nuclear Information System (INIS)

    Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (Ptrend < 0.001), which was stronger among MMR deficient cases (heterogeneity P = 0.059). Other worth noting associations, of borderline statistical significance after multiple testing correction, were a positive association between diets high in oven-broiled short ribs or spareribs and CRC risk (Ptrend = 0.002), which was also stronger among MMR-deficient cases, and an inverse association with grilled hamburgers (Ptrend = 0.002). Our results support the role of specific meat types and cooking practices as possible sources of human carcinogens relevant for CRC risk

  11. Variants in estrogen-biosynthesis genes CYP17 and CYP19 and breast cancer risk: a family-based genetic association study

    International Nuclear Information System (INIS)

    Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first family-based association study examining associations between female breast cancer risk and polymorphisms in two key estrogen-biosynthesis genes CYP17 (T→C promoter polymorphism) and CYP19 (TTTA repeat polymorphism). We conducted the study among 278 nuclear families containing one or more daughters with breast cancer, with a total of 1123 family members (702 with available constitutional DNA and questionnaire data and 421 without them). These nuclear families were selected from breast cancer families participating in the Metropolitan New York Registry, one of the six centers of the National Cancer Institute's Breast Cancer Family Registry. We used likelihood-based statistical methods to examine allelic associations. We found the CYP19 allele with 11 TTTA repeats to be associated with breast cancer risk in these families. We also found that maternal (but not paternal) carrier status of CYP19 alleles with 11 repeats tended to be associated with breast cancer risk in daughters (independently of the daughters' own genotype), suggesting a possible in utero effect of CYP19. We found no association of a woman's breast cancer risk either with her own or with her mother's CYP17 genotype. This family-based study indicates that a woman's personal and maternal carrier status of CYP19 11 TTTA repeat allele might be related to increased breast cancer risk. However, because this is the first study to report an association between CYP19 11 TTTA repeat allele and breast cancer, and because multiple comparisons have been made, the associations should be interpreted with caution and need confirmation in future family-based studies

  12. Large genomic rearrangement of BRCA1 and BRCA2 genes in familial breast cancer patients in Korea.

    Science.gov (United States)

    Cho, Ja Young; Cho, Dae-Yeon; Ahn, Sei Hyun; Choi, Su-Youn; Shin, Inkyung; Park, Hyun Gyu; Lee, Jong Won; Kim, Hee Jeong; Yu, Jong Han; Ko, Beom Seok; Ku, Bo Kyung; Son, Byung Ho

    2014-06-01

    We screened large genomic rearrangements of the BRCA1 and BRCA2 genes in Korean, familial breast cancer patients. Multiplex ligation-dependent probe amplification assay was used to identify BRCA1 and BRCA2 genomic rearrangements in 226 Korean familial breast cancer patients with risk factors for BRCA1 and BRCA2 mutations, who previously tested negative for point mutations in the two genes. We identified only one large deletion (c.4186-1593_4676-1465del) in BRCA1. No large rearrangements were found in BRCA2. Our result indicates that large genomic rearrangement in the BRCA1 and BRCA2 genes does not seem like a major determinant of breast cancer susceptibility in the Korean population. A large-scale study needs to validate our result in Korea.

  13. How do women at increased, but unexplained, familial risk of breast cancer perceive and manage their risk? A qualitative interview study

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    Keogh Louise A

    2011-09-01

    Full Text Available Abstract Background The perception of breast cancer risk held by women who have not had breast cancer, and who are at increased, but unexplained, familial risk of breast cancer is poorly described. This study aims to describe risk perception and how it is related to screening behaviour for these women. Methods Participants were recruited from a population-based sample (the Australian Breast Cancer Family Study - ABCFS. The ABCFS includes women diagnosed with breast cancer and their relatives. For this study, women without breast cancer with at least one first- or second-degree relative diagnosed with breast cancer before age 50 were eligible unless a BRCA1 or BRCA2 mutation had been identified in their family. Data collection consisted of an audio recorded, semi-structured interview on the topic of breast cancer risk and screening decision-making. Data was analysed thematically. Results A total of 24 interviews were conducted, and saturation of the main themes was achieved. Women were classified into one of five groups: don't worry about cancer risk, but do screening; concerned about cancer risk, so do something; concerned about cancer risk, so why don't I do anything?; cancer inevitable; cancer unlikely. Conclusions The language and framework women use to describe their risk of breast cancer must be the starting point in attempts to enhance women's understanding of risk and their prevention behaviour.

  14. Younger age of onset and multiple primary lesions associated with esophageal squamous cell carcinoma cases with a positive family history of the cancer suggests genetic predisposition

    Institute of Scientific and Technical Information of China (English)

    Jia Nan; Wen Xiaoduo; Zhang Nan; Yang Yi; Zhang Liwei; Wang Xiaoling; Wang Na

    2014-01-01

    Background Previous epidemiological studies have consistently found a positive family history of esophageal cancer is associated with a significantly increased risk of the cancer.However,whether the elevated risk could be attributed to common household exposure or inherited susceptibility is uncertain.This study aimed to highlight the effect of genetic predisposition by noting the significant differences in onset age and multiple primary cancers between esophageal squamous cell carcinoma (ESCC) cases with or without a positive family history of the cancer.Methods Age at onset and the percentage of multiple primary cancers were compared between ESCCs with (n=766) or without (n=1 776) a positive family history of the cancer in a consecutive surgery cohort at the Department of Thoracic Surgery of Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University.Results Overall,ESCCs with a positive family history of the cancer featured both a significantly younger age of onset and significantly more multiple primary cancers than those with a negative family history (onset age 51.83 vs.53.49 years old,P <0.01; percent of multiple primary cancers 5.50% vs.1.70%,x2=25.42,P <0.01).Both the differences were evident in subgroup analyses,but did not correlate.While age at onset differed significantly by family history among the male,smoking,and drinking groups,the difference of multiple primary cancers was significant among the otherwise nonsmoking,nondrinking,and younger onset age groups.Conclusions Younger age of onset and multiple primary cancers associated with ESCCs with a positive,as opposed to a negative family history of the cancer,suggest a genetic predisposition.The results of subgroup analyses indicate a younger age of ESCC development results from the interaction of environmental and genetic risk factors,but multiple primary cancers may be related only to genetic predisposition.

  15. Bcl2 Family Functions as Signaling Target in Nicotine-/NNK-Induced Survival of Human Lung Cancer Cells

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    Xingming Deng

    2014-01-01

    Full Text Available Lung cancer is the leading cause of cancer death and has a strong etiological association with cigarette smoking. Nicotine and nitrosamine 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK are two major components in cigarette smoke that significantly contribute to the development of human lung cancer. Nicotine is able to stimulate survival of both normal human lung epithelial and lung cancer cells. In contrast to nicotine, NNK is a more potent carcinogen that not only induces single-strand DNA breaks and oxidative DNA damage but also stimulates survival and proliferation of normal lung epithelial and lung cancer cells. However, the molecular mechanism(s by which nicotine and NNK promote cell survival, proliferation, and lung tumor development remains elusive. The fate of cells (i.e., survival or death is largely decided by the Bcl2 family members. In the past several years, multiple signaling links between nicotine/NNK and Bcl2 family members have been identified that regulate survival and proliferation. This review provides a concise, systematic overview of the current understanding of the role of the pro- or antiapoptotic proteins in cigarette smoking, lung cancer development, and treatment resistance.

  16. Family and cultural influences on cervical cancer screening among immigrant Latinas in Miami-Dade County, USA.

    Science.gov (United States)

    Madhivanan, Purnima; Valderrama, Diana; Krupp, Karl; Ibanez, Gladys

    2016-01-01

    Cervical cancer disproportionately affects minorities, immigrants and low-income women in the USA, with disparities greatest among Latino immigrants. We examined barriers and facilitators to cervical cancer screening practices among a group of immigrant Latino women in Florida, USA. Between January and May 2013, six focus group discussions, involving 35 participants, were conducted among Hispanic women in Miami to explore their knowledge, beliefs about cervical cancer and facilitators and barriers to cervical cancer screening using a theoretical framework. The data showed that family support, especially from female relatives, was an important facilitator of screening and treatment. Women, however, reported prioritising family health over their own, and some expressed fatalistic beliefs about cancer. Major obstacles to receiving a Pap smear included fear that it might result in removal of the uterus, discomfort about being seen by a male doctor and concern that testing might stigmatise them as being sexually promiscuous or having a sexually transmitted disease. Targeted education on cancer and prevention is critically needed in this population. Efforts should focus on women of all ages since younger women often turn to older female relatives for advice.

  17. First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients

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    Berinstein Neil L

    2012-08-01

    Full Text Available Abstract Background DepoVaxTM is a novel non-emulsion depot-forming vaccine platform with the capacity to significantly enhance the immunogenicity of peptide cancer antigens. Naturally processed HLA-A2 restricted peptides presented by breast, ovarian and prostate cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. Methods A phase I clinical study was designed to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients. A total of 23 late stage cancer patients were recruited and were divided into two dose/volume cohorts in a three immunization protocol. Results DPX-0907 was shown to be safe with injection site reactions being the most commonly reported adverse event. All breast cancer patients (3/3, most of ovarian (5/6 and one third of prostate (3/9 cancer patients exhibited detectable immune responses, resulting in a 61% immunological response rate. Immune responses were generally observed in patients with better disease control after their last prior treatment. Antigen-specific responses were detected in 73% of immune responders (44% of evaluable patients after the first vaccination. In 83% of immune responders (50% of evaluable patients, peptide-specific T cell responses were detected at ≥2 time points post vaccination with 64% of the responders (39% of evaluable patients showing evidence of immune persistence. Immune monitoring also demonstrated the generation of antigen-specific T cell memory with the ability to secrete multiple Type 1 cytokines. Conclusions The novel DepoVax formulation promotes multifunctional effector memory responses to peptide-based tumor associated antigens. The data supports the capacity of DPX-0907 to elicit Type-1 biased immune responses, warranting further clinical development of the vaccine. This study underscores the importance of applying vaccines in clinical settings in which patients are more likely to be

  18. The conjoint use of music therapy and reflexology with hospitalized advanced stage cancer patients and their families.

    Science.gov (United States)

    Magill, Lucanne; Berenson, Susan

    2008-09-01

    Advanced stage cancer patients experience debilitating physical symptoms as well as profound emotional and spiritual struggles. Advanced disease is accompanied by multiple changes and losses for the patient and the family. Palliative care focuses on the relief of overall suffering of patients and families, including symptom control, psychosocial support, and the meeting of spiritual needs. Music therapy and reflexology are complementary therapies that can soothe and provide comfort. When used conjointly, they provide a multifaceted experience that can aid in the reduction of anxiety, pain, and isolation; facilitate communication between patients, family members, and staff; and provide the potential for a more peaceful dying experience for all involved. This article addresses the benefits of the combined use of music therapy and reflexology. Two case studies are presented to illustrate the application and benefits of this dual approach for patients and their families regarding adjustment to the end of life in the presence of anxiety and cognitive impairment. PMID:18662423

  19. Family system characteristics and psychological adjustment to cancer susceptibility genetic testing : a prospective study

    NARCIS (Netherlands)

    van Oostrom, I.; Meijers-Heijboer, H.; Duivenvoorden, H. J.; Brocker-Vriends, A. H. J. T.; van Asperen, C. J.; Sijmons, R. H.; Seynaeve, C.; Van Gool, A. R.; Klijn, J. G. M.; Tibben, A.

    2007-01-01

    This study examined prospectively the contribution of family functioning, differentiation to parents, family communication and support from relatives to psychological distress in individuals undergoing genetic susceptibility testing for a known familial pathogenic BRCA1/2 or Hereditary nonpolyposis

  20. Overrepresentation of transcription factor families in the genesets underlying breast cancer subtypes

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    Joshi Himanshu

    2012-05-01

    Full Text Available Abstract Background The human genome contains a large amount of cis-regulatory DNA elements responsible for directing both spatial and temporal gene-expression patterns. Previous studies have shown that based on their mRNA expression breast tumors could be divided into five subgroups (Luminal A, Luminal B, Basal, ErbB2+ and Normal-like, each with a distinct molecular portrait. Whole genome gene expression analysis of independent sets of breast tumors reveals repeatedly the robustness of this classification. Furthermore, breast tumors carrying a TP53 mutation show a distinct gene expression profile, which is in strong association to the distinct molecular portraits. The mRNA expression of 552 genes, which varied considerably among the different tumors, but little between two samples of the same tumor, has been shown to be sufficient to separate these tumor subgroups. Results We analyzed in silico the transcriptional regulation of genes defining the subgroups at 3 different levels: 1. We studied the pathways in which the genes distinguishing the subgroups of breast cancer may be jointly involved including upstream regulators (1st and 2nd level of regulation as well as downstream targets of these genes. 2. Then we analyzed the promoter areas of these genes (−500 bp tp +100 bp relative to the transcription start site for canonical transcription binding sites using Genomatix. 3. We looked for the actual expression levels of the identified TF and how they correlate with the overrepresentation of their TF binding sites in the separate groups. We report that promoter composition of the genes that most strongly predict the patient subgroups is distinct. The class-predictive genes showed a clearly different degree of overrepresentation of transcription factor families in their promoter sequences. Conclusion The study suggests that transcription factors responsible for the observed expression pattern in breast cancers may lead us to important biological

  1. Novel MLH1 frameshift mutation in an extended hereditary nonpolyposis colorectal cancer family

    Institute of Scientific and Technical Information of China (English)

    Tanya Kirilova Kadiyska; Nadja Bogdanova; Ivo Marinov Kremensky; Radka Petrova Kaneva; Dimitar Georgiev Nedin; Alexandrina Borisova Alexandrova; Antonina Todorova Gegova; Stoyan Ganchev Lalchev; Tatyana Christova; Vanio Ivanov Mitev; Juergen Horst

    2006-01-01

    AIM: To present novel frameshift mutation c.31delC [p.L11X] in the MLH1 gene identified in an extended Bulgarian hereditary non-polyposis colorectal cancer (HNPCC) family and to analyze the molecular and clinical findings within the pedigree concerning the proposal of adequate individual prophylactic strategy for all mutation carriers.METHODS: The pedigree of the family consists of 42 members in four generations. Search for mutations in the MLH1 and hMSH2 genes was performed in the proband. After PCR amplification of all exons including flanking intronic regions, amplicons were directly sequenced.RESULTS: The mutation was found in nine from the thirteen pedigree members who signed informed consent to participate in the study. In three adenocarcinomas,microsatellite instability and lack of the MLH1 protein expression were detected. The only one tubulovillous adenoma analyzed was microsatellite stable and the MLH1 protein showed an intact staining.CONCLUSION: The newly described mutation c.31delC is HNPCC causative. Besides the typical clinical features of the syndrome, we found a specific pathologic manifestation such as moderate to high differentiated adenocarcinomas of the colon. One of the mutation carriers developed a benign giant cell soft tissue tumor. The primary tumor localizations were frequently extracolonic and detailed yearly gastrointestinal and gynecological examinations have been proposed to the mutation carriers.We emphasize the importance of including the HNPCC genetic counseling and testing as well in the following surveillance of all patients at risk in the services covered by the health insurance in Bulgaria.

  2. Loss of FHIT expression in gastric mucosa of patients with family histories of gastric cancer and Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Krystyna Stec-Michalska; Slawomir Antoszczyk; Grazyna Klupinska; Barbara Nawrot

    2005-01-01

    AIM: To answer the question whether FHIT gene expression is affected by the family history of gastric carcinoma and the presence of Helicobacter pylori (Hpylori) in the gastric mucosa of patients with dyspepsia.METHODS: FHIT gene expression in two different topographic sites of the gastric mucosa of twenty-one patients with dyspepsia and with or without familial gastric carcinoma, infected or not infected with H pylori, was evaluated by reverse transcription-PCR (RT-PCR) and IMAGE QUANT methods. A rapid urease test and histopathological examination were used to determine H pylori colonization.RESULTS: In the gastric mucosa of patients with family histories of gastric carcinoma, the amount of FHIT protein mRNA was reduced down to 32%, and for patients with H pylori colonization, to 24% in comparison to controls with dyspepsia and without cancer in the family. FHIT expression was independent of the topography of specimens (corpus vsantrum), and for the control patients it was less sensitive to infection with H pylori. A considerable statistical difference in FHIT levels was observed in the gastric mucosa from the corpus of patients with family histories of gastric carcinoma in respect to H pylori colonization (P = 0.06). Macroscopic evaluation of the gastric mucosa demonstrated that pathologic changes classified according to the Sydney system had no significant influence on FHIT expression within each tested group of patients.CONCLUSION: Loss of FHIT expression was observed in patients with dyspepsia and family histories of gastric carcinoma, especially those infected with H pylori. Such results may constitute an early indication of the development of gastric carcinoma, which is associated with family factors including heredity and H pylori infection. The loss of the FHIT gene may serve as a marker for early diagnosis and prevention of gastric carcinoma, especially in context of early monitoring of H pylori infection in individuals with a record of familial stomach

  3. Application of multiplex PCR with histopathologic features for detection of familial breast cancer in formalin-fixed, paraffin-embedded histologic specimens.

    Science.gov (United States)

    Rassi, H; Houshmand, M; Hashemi, M; Majidzadeh, K; Akbari, M H Hosseini; Panahi, M Shafa Shariat

    2008-01-01

    Breast cancer is the most common malignancy among females in the world. Age and familial history are the major risk factors for the development of this disease in Iran. Mutations of BRCA1 and BRCA2 genes are associated with a greatly increased risk for development of familial breast cancer. Frequency of BRCA mutations was identified in familial breast cancers (FBC) and non-familial breast cancers (NFBC) by molecular genetics, morphological and Immunohistochemical methods. Thirty forth formalin-fixed, paraffin-embedded breast tissue tumors were analyzed from 16 patients with FBC and 18 patients with NFBC. Three 5382insC mutations detected by multiplex PCR in 16 familial breast cancers. Immunohistochemical method was used to detect estrogen receptor (ER) and progesterona receptor (PR) and TP53. Comparison of ER, PR and TP53 exhibited high difference (P < 0.0001) in familial breast cancers and non-familial breast cancers. Our results demonstrated that 5382insC mutation, ER, PR, TP53, mitotic activity, polymorphism, necrosis and tubules can serve as the major risk factors for the development of FBC. PMID:18630122

  4. Breast cancer in kurdish women of northern Iraq: incidence, clinical stage, and case control analysis of parity and family risk

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    Safar Banaz M

    2009-12-01

    Full Text Available Abstract Background Breast cancer in the Middle-East occurs in relatively young women and frequently presents as advanced disease. A protective effect of multiparity is not apparent, and high familial risk is reported in some countries. This study investigates breast cancer rates and clinical stage related to age in the Kurdish region of Iraq and evaluates risk associated with parity and family history. Findings are compared with nearby countries and the West. Methods Sulaimaniyah Directorate of Health records identified 539 women diagnosed with breast cancer during 2006-2008. Clinical survey forms were completed on 296 patients and on 254 age-matched controls. Age specific incidence rates were calculated from Directorate of Health population estimates. Results Average patient age was 47.4 ± 11 years and 59.5% were pre-menopausal. Diagnosis was at clinical stage 1 for 4.1%, stage 2 for 43.5%, stage 3 for 26.0%, and stage 4 for 8.1% of patients. For 18.2%, stage was unknown. Annual breast cancer incidence rates per 100,000 women peaked at 168.9 at age 55 to 59 and declined to 57.3 at 60 and above. Patients had an average of 5.0 ± 3.3 children compared to 5.4 ± 3.5 for controls, P = 0.16. A first degree family member had breast cancer among 11.1% of patients and 2.1% of controls (P 50% of these patients and controls being ≥50 years old. No statistically significant relationship was found between tumor stage and age, P = 0.59. Conclusions In Kurdish Iraq, breast cancer is predominantly a disease of pre-menopausal women having multiple pregnancies. For younger patients, breast cancer incidence was similar to the West and possibly higher than many Middle-Eastern countries, but unlike the West, the estimated rates declined markedly in the elderly. The familial breast cancer risk for both older and younger women was within the general population risk of Western countries. Clinical stages were advanced and indicated delays in diagnosis that were

  5. Clustering of cancer among families of cases with Hodgkin Lymphoma (HL, Multiple Myeloma (MM, Non-Hodgkin's Lymphoma (NHL, Soft Tissue Sarcoma (STS and control subjects

    Directory of Open Access Journals (Sweden)

    Karunanayake Chandima P

    2009-02-01

    Full Text Available Abstract Background A positive family history of chronic diseases including cancer can be used as an index of genetic and shared environmental influences. The tumours studied have several putative risk factors in common including occupational exposure to certain pesticides and a positive family history of cancer. Methods We conducted population-based studies of Hodgkin lymphoma (HL, Multiple Myeloma (MM, non-Hodgkin's Lymphoma (NHL, and Soft Tissue Sarcoma (STS among male incident case and control subjects in six Canadian provinces. The postal questionnaire was used to collect personal demographic data, a medical history, a lifetime occupational history, smoking pattern, and the information on family history of cancer. The family history of cancer was restricted to first degree relatives and included relationship to the index subjects and the types of tumours diagnosed among relatives. The information was collected on 1528 cases (HL (n = 316, MM (n = 342, NHL (n = 513, STS (n = 357 and 1506 age ± 2 years and province of residence matched control subjects. Conditional logistic regression analyses adjusted for the matching variables were conducted. Results We found that most families were cancer free, and a minority included two or more affected relatives. HL [(ORadj (95% CI 1.79 (1.33, 2.42], MM (1.38(1.07, 1.78, NHL (1.43 (1.15, 1.77, and STS cases (1.30(1.00, 1.68 had higher incidence of cancer if any first degree relative was affected with cancer compared to control families. Constructing mutually exclusive categories combining "family history of cancer" (yes, no and "pesticide exposure ≥10 hours per year" (yes, no indicated that a positive family history was important for HL (2.25(1.61, 3.15, and for the combination of the two exposures increased risk for MM (1.69(1.14,2.51. Also, a positive family history of cancer both with (1.72 (1.21, 2.45 and without pesticide exposure (1.43(1.12, 1.83 increased risk of NHL. Conclusion HL, MM, NHL

  6. An analysis of phenotypic variation in the familial cancer syndrome von Hippel-Lindau disease: evidence for modifier effects.

    OpenAIRE

    Webster, A. R.; Richards, F. M.; MacRonald, F E; Moore, A T; Maher, E. R.

    1998-01-01

    von Hippel-Lindau disease (VHL) is a dominantly inherited familial cancer syndrome predisposing to ocular and CNS hemangioblastomas, renal-cell carcinoma (RCC), and pheochromocytoma. Both interfamilial and intrafamilial variability in expression is well recognized. Interfamilial differences in pheochromocytoma susceptibility have been attributed to allelic heterogeneity such that specific missense germ-line mutations confer a high risk for this complication. However, in most cases, tumor susc...

  7. PGC-1 family coactivators and cell fate: roles in cancer, neurodegeneration, cardiovascular disease and retrograde mitochondria-nucleus signalling.

    OpenAIRE

    Jones, A W; Z. Yao; Vicencio, J. M.; Karkucinska-Wieckowska, A.; Szabadkai, G.

    2012-01-01

    Over the past two decades, a complex nuclear transcriptional machinery controlling mitochondrial biogenesis and function has been described. Central to this network are the PGC-1 family coactivators, characterised as master regulators of mitochondrial biogenesis. Recent literature has identified a broader role for PGC-1 coactivators in both cell death and cellular adaptation under conditions of stress, here reviewed in the context of the pathology associated with cancer, neurodegeneration and...

  8. Alternative treatments for melanoma: targeting BCL-2 family members to de-bulk and kill cancer stem cells

    OpenAIRE

    Mukherjee, Nabanita; Schwan, Josianna V.; Fujita, Mayumi; Norris, David A.; Shellman, Yiqun G.

    2015-01-01

    For the first time new treatments in melanoma have produced significant responses in advanced diseases, but 30–90% of melanoma patients do not respond or eventually relapse after the initial response to the current treatments. The resistance of these melanomas is likely due to tumor heterogeneity, which may be explained by models such as the stochastic, hierarchical, and phenotype-switching models. This review will discuss the recent advancements in targeting BCL-2 family members for cancer t...

  9. Genome-wide sequencing to identify the cause of hereditary cancer syndromes: with examples from familial pancreatic cancer

    OpenAIRE

    Roberts, Nicholas J.; Klein, Alison P.

    2012-01-01

    Advances in our understanding of the human genome and next-generation technologies have facilitated the use of genome-wide sequencing to decipher the genetic basis of Mendelian disease and hereditary cancer syndromes. The application of genome-wide sequencing in hereditary cancer syndromes has had mixed success, in part, due to complex nature of the underlying genetic architecture. In this review we discuss the use of genome-wide sequencing in both Mendelian diseases and hereditary cancer syn...

  10. γ-ray hypersensitivity and faulty DNA repair in cultured cells from humans exhibiting familial cancer proneness

    International Nuclear Information System (INIS)

    The most significant danger to irradiated individuals is the induction of cancer. Ataxia telangiectasia (AT) is known as a disorder linking radiosensitivity with cancer proneness, and AT is a rare inherited disorder. This is the degenerative multisystem affliction that is transmitted as a simple autosomal recessive trait. Cell culture studies disclosed the relationship between the cellular hypersensitivity to γ-ray inactivation in vitro and the propensity to develop cancer in vivo. The molecular evidence for the defects in the repair of radiogenic DNA damage has as yet been obtained only for AT, and it seems likely that anomalous DNA repair may not be the key causal factor in the development of some of the clinical abnormalities associated with the disease, including the tendency to develop lymphoproliferative cancer. Nevertheless, AT, Rothmund-Thomson syndrome (RTS), and acute myelogenous leukemia (AML) family show promise as the models for elucidating the importance of cellular radiosensitivity and imperfect DNA repair in the induction of cancer by radiation and radiomimetic carcinogens in the biosphere. Expanded efforts are required to identify heterozygosity for the AT genes in general population and to assess the role of the interaction between this genetic make-up and environmental carcinogens in the occurrence of common cancers. (Yamashita, S.)

  11. Ability of FDG-PET to detect all cancers in patients with familial adenomatous polyposis, and impact on clinical management

    Energy Technology Data Exchange (ETDEWEB)

    Kouwen, Mariette C.A. van; Drenth, Joost P.H.; Friederich, Pieter; Nagengast, Fokko M. [Radboud University Nijmegen Medical Centre, Department of Gastroenterology and Hepatology, 9101, Nijmegen (Netherlands); Krieken, J. Han J.M. van [Radboud University Nijmegen Medical Centre, Department of Pathology, Nijmegen (Netherlands); Goor, Harry van [Radboud University Nijmegen Medical Centre, Department of Surgery, Nijmegen (Netherlands); Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2006-03-15

    Familial adenomatous polyposis (FAP) is characterised by colonic and duodenal adenomatous polyps that carry a risk of malignant transformation. Malignant degeneration of duodenal adenomas is difficult to detect. We speculated that 2-({sup 18}F)-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) might be able to detect early duodenal cancer in FAP. Accordingly, we investigated the role of FDG-PET in the management of FAP patients. FDG-PET was performed in 24 FAP patients. Eight had advanced duodenal adenomas (Spigelman IV), including two patients with duodenal cancer. Scans were defined as positive on the basis of focal FDG accumulation. Pathological FDG accumulation was absent in 19 of 24 patients. All six patients with Spigelman IV duodenal adenomas (without cancer) were negative; two of these underwent a duodenectomy and pathological examination did not reveal duodenal cancer. In five patients, FDG-PET revealed significant uptake, in the duodenum (2), lower abdomen (1), lung (1) and multiple sites in the abdomen (1). These hot spots correlated with duodenal cancer (2), abdominal metastasis (1) and sclerosing haemangioma of the lung (1). We failed to make a histopathological diagnosis in the single patient with multiple intra-abdominal sites of FDG uptake. None of the patients from the FDG-PET-negative group developed cancer during follow-up (mean 2.8 years). (orig.)

  12. Screening of 1331 Danish breast and/or ovarian cancer families identified 40 novel BRCA1 and BRCA2 mutations

    DEFF Research Database (Denmark)

    Hansen, Thomas V O; Jønson, Lars; Steffensen, Ane Y;

    2011-01-01

    Germ-line mutations in the tumour suppressor genes BRCA1 and BRCA2 predispose to breast and ovarian cancer. Since 1999 we have performed mutational screening of breast and/or ovarian cancer patients in East Denmark. During this period we have identified 40 novel sequence variations in BRCA1...... and BRCA2 in high risk breast and/or ovarian cancer families. The mutations were detected via pre-screening using dHPLC or high-resolution melting and direct sequencing. We identified 16 variants in BRCA1, including 9 deleterious frame-shift mutations, 2 intronic variants, 4 missense mutations, and 1...... interpreted as pathogenic, 3 missense mutations were suggested to be pathogenic based on in silico analysis, 6 mutations were suggested to be benign since they were identified in patients together with a well-known disease-causing BRCA1/BRCA2 mutation, while 12 were variants of unknown significance....

  13. Influence of family history, irradiation and anti-cancer drug (mitomycin C) on the occurrence of multiple primary neoplasms in breast carcinoma patients

    International Nuclear Information System (INIS)

    The influence of family history, irradiation and anti-cancer drug (Mitomycin C) on the occurrence of multiple primary neoplasms was analysed using the person-year method in 1359 Japanese breast carcinoma patients. There were 111 multiple primary neoplasms, including bilaterl breast cancer, in 109 patients; the incidence rate was 0.0072 per person-year. The incidence rate in patients with a family history of cancer was 1.29 times higher than in those without. In the bilateral breast cancer group there was about a 3 times higher frequency of family history of breast cancer. Irradiation therapy raised the occurrence of multiple primary neoplasms 1.28 fold, and Mitomycin C (40 mg) had no effect on the occurrence of neoplasms during a 10-year observation period. (author)

  14. Online parent-targeted cognitive-behavioural therapy intervention to improve quality of life in families of young cancer survivors: study protocol for a randomised controlled trial

    OpenAIRE

    Wakefield, Claire E; Sansom-Daly, Ursula M; McGill, Brittany C; McCarthy, Maria; Girgis, Afaf; Grootenhuis, Martha; Barton, Belinda; Patterson, Pandora; Osborn, Michael; Lowe, Cherie; Anazodo, Antoinette; Miles, Gordon; Cohn, Richard J.

    2015-01-01

    Background Due to advances in multimodal therapies, most children survive cancer. In addition to the stresses of diagnosis and treatment, many families are now navigating the challenges of survivorship. Without sufficient support, the ongoing distress that parents experience after their child’s cancer treatment can negatively impact the quality of life and psychological wellbeing of all family members. Methods/Design The ‘Cascade’ (Cope, Adapt, Survive: Life after C AncEr) study is a three-ar...

  15. Detection of Clonal and Subclonal Copy-Number Variants in Cell-Free DNA from Patients with Breast Cancer Using a Massively Multiplexed PCR Methodology

    Directory of Open Access Journals (Sweden)

    Eser Kirkizlar

    2015-10-01

    Using an in vitro model of cell-free DNA, we show that mmPCR-NGS can accurately detect CNVs with average allelic imbalances as low as 0.5%, an improvement over previously reported whole-genome sequencing approaches. Our method revealed differences in the spectrum of CNVs detected in tumor tissue subsections and matching plasma samples from 11 patients with stage II breast cancer. Moreover, we showed that liquid biopsies are able to detect subclonal mutations that may be missed in tumor tissue biopsies. We anticipate that this mmPCR-NGS methodology will have broad applicability for the characterization, diagnosis, and therapeutic monitoring of CNV-enriched cancers, such as breast, ovarian, and lung cancer.

  16. Developing a Cancer Survivorship Curriculum for Family Medicine Residents: A Needs Assessment

    Science.gov (United States)

    Schubart, Jane R.; Gusani, Niraj J.; Kass, Rena; Lewis, Peter

    2013-01-01

    With the increasing survival of cancer patients, primary care residents must be familiar with the late effects of cancer treatment and be able to offer appropriate survivorship care in partnership with cancer care specialists. To address these paired public health and educational needs, an interdisciplinary group at our institution is developing,…

  17. A micro costing of NHS cancer genetic services

    Science.gov (United States)

    Griffith, G L; Tudor-Edwards, R; Gray, J; Butler, R; Wilkinson, C; Turner, J; France, B; Bennett, P

    2004-01-01

    This paper presents the first full micro costing of a commonly used cancer genetic counselling and testing protocol used in the UK. Costs were estimated for the Cardiff clinic of the Cancer Genetics Service in Wales by issuing a questionnaire to all staff, conducting an audit of clinic rooms and equipment and obtaining gross unit costs from the finance department. A total of 22 distinct event pathways were identified for patients at risk of developing breast, ovarian, breast and ovarian or colorectal cancer. The mean cost per patient were £97–£151 for patients at moderate risk, £975–£3072 for patients at high risk of developing colorectal cancer and £675–£2909 for patients at high risk of developing breast or ovarian cancer. The most expensive element of cancer genetic services was labour. Labour costs were dependent upon the amount of labour, staff grade, number of counsellors used and the proportion of staff time devoted to indirect patient contact. With the growing demand for cancer genetic services and the growing number of national and regional cancer genetic centers, there is a need for the different protocols being used to be thoroughly evaluated in terms of costs and outcomes. PMID:15583691

  18. Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations

    NARCIS (Netherlands)

    Brohet, Richard M.; Velthuizen, Maria E.; Hogervorst, Frans B. L.; Meijers-Heijboer, Hanne E. J.; Seynaeve, Caroline; Collee, Margriet J.; Verhoef, Senno; Ausems, Margreet G. E. M.; Hoogerbrugge, Nicoline; van Asperen, Christi J.; Garcia, Encarna Gomez; Menko, Fred; Oosterwijk, Jan C.; Devilee, Peter; van't Veer, Laura J.; van Leeuwen, Flora E.; Easton, Douglas F.; Rookus, Matti A.; Antoniou, Antonis C.

    2014-01-01

    Background BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian cancer, but risks have been found to vary across studies and populations. Methods We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and studied the variation in breast and ovarian cancer risks using a mod

  19. Quality of Life and Mortality of Long-Term Colorectal Cancer Survivors in the Seattle Colorectal Cancer Family Registry

    OpenAIRE

    Adams, Scott V.; Rachel Ceballos; Newcomb, Polly A.

    2016-01-01

    Background and Aim Because most colorectal cancer patients survive beyond five years, understanding quality of life among these long-term survivors is essential to providing comprehensive survivor care. We sought to identify personal characteristics associated with reported quality of life in colorectal cancer survivors, and sub-groups of survivors potentially vulnerable to very low quality of life. Methods We assessed quality of life using the Veterans RAND 12-item Health Survey within a pop...

  20. A risk prediction algorithm for ovarian cancer incorporating BRCA1, BRCA2, common alleles and other familial effects

    Science.gov (United States)

    Jervis, Sarah; Song, Honglin; Lee, Andrew; Dicks, Ed; Harrington, Patricia; Baynes, Caroline; Manchanda, Ranjit; Easton, Douglas F; Jacobs, Ian; Pharoah, Paul P D; Antoniou, Antonis C

    2015-01-01

    Background Although BRCA1 and BRCA2 mutations account for only ∼27% of the familial aggregation of ovarian cancer (OvC), no OvC risk prediction model currently exists that considers the effects of BRCA1, BRCA2 and other familial factors. Therefore, a currently unresolved problem in clinical genetics is how to counsel women with family history of OvC but no identifiable BRCA1/2 mutations. Methods We used data from 1548 patients with OvC and their relatives from a population-based study, with known BRCA1/2 mutation status, to investigate OvC genetic susceptibility models, using segregation analysis methods. Results The most parsimonious model included the effects of BRCA1/2 mutations, and the residual familial aggregation was accounted for by a polygenic component (SD 1.43, 95% CI 1.10 to 1.86), reflecting the multiplicative effects of a large number of genes with small contributions to the familial risk. We estimated that 1 in 630 individuals carries a BRCA1 mutation and 1 in 195 carries a BRCA2 mutation. We extended this model to incorporate the explicit effects of 17 common alleles that are associated with OvC risk. Based on our models, assuming all of the susceptibility genes could be identified we estimate that the half of the female population at highest genetic risk will account for 92% of all OvCs. Conclusions The resulting model can be used to obtain the risk of developing OvC on the basis of BRCA1/2, explicit family history and common alleles. This is the first model that accounts for all OvC familial aggregation and would be useful in the OvC genetic counselling process. PMID:26025000

  1. Improving awareness of cancer clinical trials among Hispanic patients and families: audience segmentation decisions for a media intervention.

    Science.gov (United States)

    Quinn, Gwendolyn P; McIntyre, Jessica; Gonzalez, Luis E; Antonia, Teresita Muñoz; Antolino, Prado; Wells, Kristen J

    2013-01-01

    Clinical trials hold great promise for cancer treatment; yet, Hispanic cancer patients have low rates of clinical trial participation. Lack of awareness and knowledge of clinical trials and language barriers may account for low participation rates. Patient education through audiovisual materials can improve knowledge of and attitudes toward clinical trials among Hispanic populations. In this study, 36 Hispanic cancer patients/survivors and caregivers in Florida and Puerto Rico participated in focus groups to aid in developing a Spanish-language DVD and booklet intervention designed to increase knowledge about clinical trials. Focus group results showed (a) low levels of knowledge about clinical trials, (b) uncertainty about why a physician would expect a patient to make a choice about treatment, and (c) desire for family participation in decision making. Respondents expressed various preferences for aspects of the DVD such as showing extended family in the DVD and physician explanations about key terms. On the basis of these preferences, the authors developed a creative brief for a DVD. The content of the DVD was reviewed by Hispanic community leaders and key stakeholders. A final DVD was created, in Spanish, using Hispanic patients and physicians, which contained the information deemed important from the focus groups and stakeholder interviews. The DVD is complete with companion booklet and currently undergoing a randomized control trial.

  2. Analysis of Somatic Mutations in Cancer: Molecular Mechanisms of Activation in the ErbB Family of Receptor Tyrosine Kinases

    International Nuclear Information System (INIS)

    The ErbB/EGFR/HER family of kinases consists of four homologous receptor tyrosine kinases which are important regulatory elements in many cellular processes, including cell proliferation, differentiation, and migration. Somatic mutations in, or over-expression of, the ErbB family is found in many cancers and is correlated with a poor prognosis; particularly, clinically identified mutations found in non-small-cell lung cancer (NSCLC) of ErbB1 have been shown to increase its basal kinase activity and patients carrying these mutations respond remarkably to the small tyrosine kinase inhibitor gefitinib. Here, we analyze the potential effects of the currently catalogued clinically identified mutations in the ErbB family kinase domains on the molecular mechanisms of kinase activation. Recently, we identified conserved networks of hydrophilic and hydrophobic interactions characteristic to the active and inactive conformation, respectively. Here, we show that the clinically identified mutants influence the kinase activity in distinctive fashion by affecting the characteristic interaction networks

  3. Clinico-morphological patterns of breast cancer including family history in a New Delhi hospital, India-A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Chintamani

    2005-10-01

    Full Text Available Abstract Background Breast cancer is the second most common malignancy among women, next to cervix cancer. Understanding its pathogenesis, morphological features and various risk-factors, including family history holds a great promise for the treatment, early detection and prevention of this cancer. Patients and methods In an attempt to evaluate the clinico-morphological patterns of breast cancer patients, including their family history of breast and/or other cancers, a detailed analysis of 569 breast cancer cases diagnosed during the years 1989–2003 was carried out. Mean and standard deviation and Odds ratios along with 95% confidence intervals were estimated. χ2/Fisher's exact test were employed to test for proportions. Results Mean age of the patient at presentation was 47.8 years, ranging from 13–82 years. Among the various histo-morphological types, Infiltrating duct carcinoma (IDC was found to be commonest type i.e. in 502 cases (88.2%, followed by infiltrating lobular carcinoma (ILC in 21 cases (3.7% and other types forming 9(1%. Out of 369 cases where TNM staging was available, stage IIIB (35.2% was the commonest. Lymph node positivity was observed in 296 cases (80.2%. Out of 226 cases evaluated for presence of family history, 47 cases (20.7% revealed positive family history of cancer, among which breast or ovarian cancer were the commonest type (72.0%. Patients below 45 years of age had more frequent occurrence of family history as compared to above 45 years. Amongst familial cases, Infiltrating duct carcinoma was the commonest form accounting for 68.8% cases while ILC was found to be in a higher proportion (12.5% as compared to non- familial cases (5.4%. Conclusion Among the various determining factors for development of breast cancer and for its early detection, family history of cancer forms one of the major risk factor. It is important to take an appropriate history for eliciting information pertaining to occurrence of cancers

  4. Linkage analysis in a large Swedish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 9q22.32-31.1

    DEFF Research Database (Denmark)

    Skoglund, J; Djureinovic, T; Zhou, X-L;

    2006-01-01

    dominantly inherited colorectal cancer risk. Recently, a locus on chromosome 9q22.2-31.2 was identified by linkage analysis in sib pairs with colorectal cancer or adenoma. METHODS: Linkage analysis for the suggested locus on chromosome 9 was carried out in an extended Swedish family. This family had...... previously been investigated but following the identification of adenomas in several previously unaffected family members, these subjects were now considered to be gene carriers. RESULTS: In the present study, we found linkage of adenoma and colorectal cancer to chromosome 9q22.32-31.1 with a multipoint LOD...... score of 2.4. We were also able to define the region for this locus to 7.9 cM between the markers D9S280 and D9S277. CONCLUSIONS: Our result supports the presence of a susceptibility locus predisposing to adenoma and colorectal cancer in this chromosomal region....

  5. Investigation of single-strand conformational polymorphism of the TP53 gene in women with a family history of breast cancer

    Directory of Open Access Journals (Sweden)

    R.R. Burbano

    2000-11-01

    Full Text Available Breast cancer in families with germ line mutations in the TP53 gene has been described in the medical literature. Mutation screening for susceptibility genes should allow effective prophylactic and preventive measures. Using single-strand conformational polymorphism, we screened for mutations in exons 5, 6, 7 and 8 of gene TP53 in the peripheral blood of 8 young non-affected members (17 to 36 years old of families with a history of breast cancer. Studies of this type on young patients (mean age, 25 years are very rare in the literature. The identification of these mutations would contribute to genetic counseling of members of families with predisposition to breast cancer. The results obtained did not show any polymorphism indicating mutation. In our sample, the familial tumorigenesis is probably related to other gene etiologies.

  6. Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state-of-the-science review.

    Science.gov (United States)

    Lowery, Jan T; Ahnen, Dennis J; Schroy, Paul C; Hampel, Heather; Baxter, Nancy; Boland, C Richard; Burt, Randall W; Butterly, Lynn; Doerr, Megan; Doroshenk, Mary; Feero, W Gregory; Henrikson, Nora; Ladabaum, Uri; Lieberman, David; McFarland, Elizabeth G; Peterson, Susan K; Raymond, Martha; Samadder, N Jewel; Syngal, Sapna; Weber, Thomas K; Zauber, Ann G; Smith, Robert

    2016-09-01

    Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care. Existing data show that having 1 affected first-degree relative (FDR) increases the CRC risk 2-fold, and the risk increases with multiple affected FDRs and a younger age at diagnosis. There is variability in screening recommendations across consensus guidelines. Screening adherence is communication are important barriers. Effective interventions incorporate strategies for overcoming barriers, but these have not been broadly tested in clinical settings. Four strategies for reducing CRC in persons with familial risk are suggested: 1) improving the collection and utilization of the FH of cancer, 2) establishing a consensus for screening guidelines by FH, 3) enhancing provider-patient knowledge of guidelines and communication about CRC risk, and 4) encouraging survivors to promote screening within their families and partnering with existing screening programs to expand their reach to high-risk groups. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2633-2645. © 2016 American Cancer Society. PMID:27258162

  7. A novel mutation in the CDH1 gene in a Spanish family with hereditary diffuse gastric cancer.

    Science.gov (United States)

    López, María; Cervera-Acedo, Cristina; Santibáñez, Paula; Salazar, Raquel; Sola, Jesús-Javier; Domínguez-Garrido, Elena

    2016-01-01

    Hereditary diffuse gastric cancer (HDGC) is an inherited form of diffuse type gastric cancer. Germline CDH1 mutations have been identified in approximately 15-50 % of affected kindred that meet the clinical criteria for HDGC. If any of the criteria is met the individual is referred to genetic counseling and CDH1 testing is offered. In this report we present the case of a Spanish family with HDGC harboring a novel CDH1 mutation. A 47 year-old female with a diagnostic of gastric adenocarcinoma and some of her relatives were tested. Study of the entire CDH1 gene, including intron-exon boundaries, by PCR and sequencing and immunohistochemical determination of the expression of E-cadherin were performed. A novel heterozygous deletion in exon 9 of CDH1 gene (c.1220_1220delC, p.P407Qfs10), was found in the proband, one sister and a nephew. It generates a premature stop codon giving rise to a truncated protein that leads to a pathogenic variant. Expression of E-cadherin was absent or frankly reduced in the proband's tumor but normal in tumor cells of great-uncle. After these results, the sister underwent prophylactic total gastrectomy, and the nephew is under annual endoscopic surveillance. Personal or familial history of diffuse gastric cancer, above all at young age, should encourage CDH1 genetic testing. In this sense, the review of the criteria and the addition in the last guideline of the recommendation: "other families in which genetic testing may also be considered" broadens the number of individuals at risk detected. Since there are not reliable methods for early detection, DGC is usually diagnosed at an advanced stage and consequently associated with a poorer outcome. Thus, CDH1 mutations detection contributes to an improvement in diagnosis and therapeutic intervention.

  8. A novel mutation in the CDH1 gene in a Spanish family with hereditary diffuse gastric cancer.

    Science.gov (United States)

    López, María; Cervera-Acedo, Cristina; Santibáñez, Paula; Salazar, Raquel; Sola, Jesús-Javier; Domínguez-Garrido, Elena

    2016-01-01

    Hereditary diffuse gastric cancer (HDGC) is an inherited form of diffuse type gastric cancer. Germline CDH1 mutations have been identified in approximately 15-50 % of affected kindred that meet the clinical criteria for HDGC. If any of the criteria is met the individual is referred to genetic counseling and CDH1 testing is offered. In this report we present the case of a Spanish family with HDGC harboring a novel CDH1 mutation. A 47 year-old female with a diagnostic of gastric adenocarcinoma and some of her relatives were tested. Study of the entire CDH1 gene, including intron-exon boundaries, by PCR and sequencing and immunohistochemical determination of the expression of E-cadherin were performed. A novel heterozygous deletion in exon 9 of CDH1 gene (c.1220_1220delC, p.P407Qfs10), was found in the proband, one sister and a nephew. It generates a premature stop codon giving rise to a truncated protein that leads to a pathogenic variant. Expression of E-cadherin was absent or frankly reduced in the proband's tumor but normal in tumor cells of great-uncle. After these results, the sister underwent prophylactic total gastrectomy, and the nephew is under annual endoscopic surveillance. Personal or familial history of diffuse gastric cancer, above all at young age, should encourage CDH1 genetic testing. In this sense, the review of the criteria and the addition in the last guideline of the recommendation: "other families in which genetic testing may also be considered" broadens the number of individuals at risk detected. Since there are not reliable methods for early detection, DGC is usually diagnosed at an advanced stage and consequently associated with a poorer outcome. Thus, CDH1 mutations detection contributes to an improvement in diagnosis and therapeutic intervention. PMID:27512640

  9. Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

    Tadateru Maehata; Fumio Itoh; Hiroaki Taniguchi; Hiroyuki Yamamoto; Katsuhiko Nosho; Yasushi Adachi; Nobuki Miyamoto; Chic Miyamoto; Noriyuki Akutsu; Satoshi Yamaoka

    2008-01-01

    AIM:To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer.METHODS:We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR,tissue microarray analysis,and methylation specific PCR (MSP).Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor.WST-8 assays and in vitro invasion assays after treatment with specific siRNA for those genes were performed.RESULTS:Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues.This was correlated with promoter hypermethylation.There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer.In colorectal cancers with beta-catenin over-expression,Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without.Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION:Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis.

  10. Keeping It in the Family: ATRX Loss Promotes Persistent Sister Telomere Cohesion in ALT Cancer Cells.

    Science.gov (United States)

    Roake, Caitlin M; Artandi, Steven E

    2015-09-14

    In this issue of Cancer Cell, Ramamoorthy and Smith report that cancer cells that maintain their chromosome ends through alternative lengthening of telomeres (ALT) display persistent sister telomere cohesion. This delayed resolution of sister telomere cohesion depends upon the loss of ATRX and its histone-sequestering function and is associated with increased recombination between sister telomeres. PMID:26373274

  11. Role Of Family Planning Practices In The Control And Prevention of Uterine Cervical Cancer- A Multivariate Analysis

    Directory of Open Access Journals (Sweden)

    Sharma S

    1995-01-01

    Full Text Available Research Question: Does acceptance of family planning reduce the risk of uterine cervical cancer? Objective: To study the association between usage of contraceptive methods and cervical carcinogenesis. Study design: Case control study. Settings: Urban Area â€" Hospital Based. Participants: 160 women having different degrees of dysplasia and 173 women having normal pap smears. Statistical Analysis: Multivariate Analysis. Results: None of the three widely prevalent Family Planning practices viz. IUD condoms and tubectomy turned out to be significant in the development of dysplasia, however, age at consummation of marriage before 18 years and illiteracy were significant. Use of IUD offered protection against carcinoma in situ (CIS and disease of invasive nature. Non- users of condoms were also at risk marginally failing to attain statistical significance.

  12. Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, and Urologic Cancers

    Science.gov (United States)

    2016-07-12

    Healthy, no Evidence of Disease; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Psychosocial Effects of Cancer and Its Treatment; Recurrent Bladder Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Uterine Sarcoma; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage II Bladder Cancer; Stage II Renal Cell Cancer; Stage II Urethral Cancer; Stage IIA Cervical Cancer; Stage IIA Colon Cancer; Stage IIA Gastric Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIA Uterine Sarcoma; Stage IIB Cervical Cancer; Stage IIB Colon Cancer; Stage IIB Gastric Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIB Uterine Sarcoma; Stage IIC Colon Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Rectal Cancer; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage III Urethral Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Cervical Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal

  13. Pancreatic Cancer Early Detection Program

    Science.gov (United States)

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  14. Screening of 1331 Danish breast and/or ovarian cancer families identified 40 novel BRCA1 and BRCA2 mutations

    DEFF Research Database (Denmark)

    Hansen, Thomas V O; Jønson, Lars; Steffensen, Ane Y;

    2011-01-01

    and BRCA2 in high risk breast and/or ovarian cancer families. The mutations were detected via pre-screening using dHPLC or high-resolution melting and direct sequencing. We identified 16 variants in BRCA1, including 9 deleterious frame-shift mutations, 2 intronic variants, 4 missense mutations, and 1...... synonymous variant. The remaining 24 variants were identified in BRCA2, including 10 deleterious mutants (6 frame-shift and 4 nonsense), 2 intronic variants, 10 missense mutations and 2 synonymous variants. The frequency of the variants of unknown significance was examined in control individuals. Moreover...

  15. The Role of miRNA in Papillary Thyroid Cancer in the Context of miRNA Let-7 Family

    Directory of Open Access Journals (Sweden)

    Ewelina Perdas

    2016-06-01

    Full Text Available Papillary thyroid carcinoma (PTC is the most common endocrine malignancy. RET/PTC rearrangement is the most common genetic modification identified in this category of cancer, increasing proliferation and dedifferentiation by the activation of the RET/PTC-RAS-BRAF-MAPK-ERK signaling pathway. Recently, let-7 miRNA was found to reduce RAS levels, acting as a tumor suppressor gene. Circulating miRNA profiles of the let-7 family may be used as novel noninvasive diagnostic, prognostic, treatment and surveillance markers for PTC.

  16. Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non-Hodgkin's lymphoma: the ESCALE study (SFCE).

    OpenAIRE

    Rudant, Jérémie; Menegaux, Florence; Leverger, Guy; Baruchel, André; Nelken, Brigitte; Bertrand, Yves; Hartmann, Olivier; Pacquement, Hélène; Vérité, Cécile; Robert, Alain; Michel, Gérard; Margueritte, Geneviève; Gandemer, Virginie; Hémon, Denis; Clavel, Jacqueline

    2007-01-01

    The role of a family history of cancer in the etiology of childhood hematopoietic malignancies was investigated using the data from the ESCALE study. ESCALE, a population-based case-control study, was carried out in France over the period, 2003-2004. A total of 773 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma (HL), 163 of non-Hodgkin's lymphoma (NHL) and 1,681 population-based controls were included. The controls were randomly selected from the French population and were frequency ...

  17. Testing a Mediational Model of Communication Among Medical Staff and Families of Cancer Patients

    Science.gov (United States)

    Gionta, Dana A.; Harlow, Lisa L.; Loitman, Jane E.; Leeman, Joanne M.

    2005-01-01

    Three structural equation models of communication between family members and medical staff were examined to understand relations among staff accessibility, inhibitory family attitudes, getting communication needs met, perceived stress, and satisfaction with communication. Compared to full and direct models, a mediational model fit best in which…

  18. Pregnane X Receptor and Cancer: Context-Specificity is Key

    Directory of Open Access Journals (Sweden)

    Satyanarayana R. Pondugula

    2016-06-01

    Full Text Available Pregnane X receptor (PXR is an adopted orphan nuclear receptor that is activated by a wide-range of endobiotics and xenobiotics, including chemotherapy drugs. PXR plays a major role in the metabolism and clearance of xenobiotics and endobiotics in liver and intestine via induction of drug-metabolizing enzymes and drug-transporting proteins. However, PXR is expressed in several cancer tissues and the accumulating evidence strongly points to the differential role of PXR in cancer growth and progression as well as in chemotherapy outcome. In cancer cells, besides regulating the gene expression of enzymes and proteins involved in drug metabolism and transport, PXR also regulates other genes involved in proliferation, metastasis, apoptosis, anti-apoptosis, inflammation, and oxidative stress. In this review, we focus on the differential role of PXR in a variety of cancers, including prostate, breast, ovarian, endometrial, and colon. We also discuss the future directions to further understand the differential role of PXR in cancer, and conclude with the need to identify novel selective PXR modulators to target PXR in PXR-expressing cancers.

  19. Why HPV Vaccine is Important to My Family: The Story of a Cervical Cancer Survivor

    Centers for Disease Control (CDC) Podcasts

    2013-05-06

    A young mom’s world is turned upside-down when she’s diagnosed with cervical cancer. Learn what she’s doing to protect her kids from HPV-related cancers.  Created: 5/6/2013 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/6/2013.

  20. Experiences and perceived needs of children and teenagers with cancer and their families

    OpenAIRE

    Pilar González Carrión

    2005-01-01

    Purpose:- To know the experiencies and perceived needs of children and teenagers with cancer and their care givers regarding the received care and their oncological process. - To identify proposals for improving care.Methodology: A qualitative study based on individual semistructured interviews and focus interviews with children and teenagers diagnosed of cancer was designed. Results: Hospitalization, therapeutic and diagnose procedures, side effects and isolation when neutropenia, were ident...

  1. New insights into the prevention and treatment of familial breast cancer.

    Science.gov (United States)

    Euhus, David M

    2011-03-15

    Individuals who inherit a deleterious mutation in BRCA1 or BRCA2 are at very high risk for breast cancer but there are several strategies available for successfully managing this risk. Breast cancers that develop in the context of germline BRCA gene mutation present challenges for management but also opportunities. DNA damaging agents, like cisplatin, and the new class of drugs called PARP inhibitors exploit the underlying defect in DNA damage repair to great effect. PMID:21337561

  2. Niclosamide inhibits colon cancer progression through downregulation of the Notch pathway and upregulation of the tumor suppressor miR-200 family.

    Science.gov (United States)

    Suliman, Mohammed A; Zhang, Zhenxing; Na, Heya; Ribeiro, Ailton L L; Zhang, Yu; Niang, Bachir; Hamid, Abdu Salim; Zhang, Hua; Xu, Lijie; Zuo, Yunfei

    2016-09-01

    Colorectal cancer (CRC) is among the most frequent causes of cancer-related deaths worldwide. Thus, there is a need for the development of new therapeutic approaches for the treatment of CRC. Accumulating evidence has revealed that niclosamide, an anthelminthic drug, exerts antitumor activity in several types of cancer, including colon cancer. However, the underlying molecular mechanisms responsible for the effects of this drug remain elusive. Previous studies have shown that the aberrant Notch signaling pathway contributes to the carcinogenesis of colon cancer. Herein, we examined the effects of niclosamide on the growth, migration and apoptosis of colon cancer cells, and the role of the Notch signaling pathway. By performing MTT, wound-healing and Transwell migration assays, we observed that niclosamide suppressed the growth and migration of colon cancer cells, and flow cytometry demonstrated that cell apoptosis was induced. This was associated with the decreased protein expression of Notch1, Notch2, Notch3 and Hey1, and the increased expression of the tumor suppressor microRNA (miR or miRNA)‑200 family members (miR‑200a, miR-200b, miR-200c, miR-141 and miR-429) that are typically downregulated in colon cancer. Collectively, these findings demonstrate that niclosamide potentially inhibits the progression of colon cancer by downregulating Notch signaling and by upregulating the miR-200 family members. PMID:27460529

  3. Insights into roles of the miR-1, -133 and -206 family in gastric cancer (Review).

    Science.gov (United States)

    Xie, Meng; Dart, Dafydd Alwyn; Owen, Sioned; Wen, Xianzi; Ji, Jiafu; Jiang, Wenguo

    2016-09-01

    Gastric cancer (GC) remains the third most common cause of cancer deaths worldwide and carries a high rate of metastatic risk contributing to the main cause of treatment failure. An accumulation of data has resulted in a better understanding of the molecular network of GC, however, gaps still exist between the unique bio-resources and clinical application. MicroRNAs are an important part of non-coding RNAs and behave as major regulators of tumour biology, alongside their well-known roles as intrinsic factors of gene expression in cellular processes, via their post-transcriptional regulation of components of signalling pathways in a coordinated manner. Deregulation of the miR-1, -133 and -206 family plays a key role in tumorigenesis, progression, invasion and metastasis. This review aims to provide a summary of recent findings on the miR-1, -133 and -206 family in GC and how this knowledge might be exploited for the development of future miRNA-based therapies for the treatment of GC. PMID:27349337

  4. A família e o processo de adoecer de câncer bucal Family and oral cancer

    Directory of Open Access Journals (Sweden)

    Mônica Cristina Batista de Melo

    2005-12-01

    Full Text Available Considerando-se que a família participa na iniciação de comportamentos sociais dos indivíduos, o presente estudo teve como objetivo investigar sua participação na adoção de hábitos considerados como fatores de risco para o câncer. O perfil sociodemográfico da população estudada (32 mulheres portadoras de câncer bucal caracterizou um quadro de pobreza social. Dentre os fatores de risco associados à doença predominaram o fumo e o álcool. Concluiu-se que a família, através dos processos de aprendizagem social e identificação, teve uma participação importante quanto à adoção das atitudes de risco.Considering that the family participates in the initiation of social behaviors of the individuals, the present study had the purpose to investigate its participation in the adoption of habits considered as risk factors of cancer. The socio-demographic profile of the studied population (32 women suffering from oral cancer was representative of social poverty. Amongst the risk factors associated to the illness were: tobacco, alcohol, and the use of dental prostheses. It was concluded that the family, through processes of social learning and identification, plaid and important role on the adoption of the risk attitudes.

  5. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... and Cancer Adjusting to Cancer Self Image & Sexuality Day-to-Day Life For Family & Friends Survivorship Questions to Ask ... Feelings & Cancer Adjusting to Cancer Self Image & Sexuality Day to Day Life Survivorship For Family & Friends Questions ...

  6. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    Energy Technology Data Exchange (ETDEWEB)

    Cekanova, Maria, E-mail: mcekanov@utk.edu [Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Fernando, Romaine I. [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Siriwardhana, Nalin [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Sukhthankar, Mugdha [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Parra, Columba de la [Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR (United States); Woraratphoka, Jirayus [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Malone, Christine [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Ström, Anders [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Baek, Seung J. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Wade, Paul A. [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Saxton, Arnold M. [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Donnell, Robert M. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Pestell, Richard G. [Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); and others

    2015-02-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis.

  7. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    International Nuclear Information System (INIS)

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis

  8. Molecular markers for tumor cell dissemination in female cancers

    International Nuclear Information System (INIS)

    In the fight against cancer many advances have been made in early detection and treatment of the disease during the last few decades. Nevertheless, many patients still die of cancer due to metastatic spreading of the disease. Tumor cell dissemination may occur very early and usually is not discovered at the time of initial diagnosis. In these cases, the mere excision of the primary tumor is an insufficient treatment. Microscopic tumor residues will remain in the blood, lymph nodes, or the bone marrow and will cause disease recurrence. To improve the patient's prognosis, a sensitive tool for the detection of single tumor cells supplementing conventional diagnostic procedures is required. As the blood is more easily accessible than the bone marrow or tissue biopsies, we intended to identify gene markers for the detection of circulating tumor cells in the blood of cancer patients. We focused on patients with breast, ovarian, endometrial or cervical cancer. Starting from a genome-wide gene expression analysis of tumor cells and blood cells, we found six genes higher expression levels in cancer patients compared to healthy women. These findings suggest that an increased expression of these genes in the blood indicates the presence of circulating tumor cells inducing future metastases and thus the need for adjuvant therapy assisting the primary treatment. Measuring the expression levels of these six genes in the blood may supplement conventional diagnostic tests and improve the patient's prognosis. (author)

  9. Familial Risk and Heritability of Cancer Among Twins in Nordic Countries

    DEFF Research Database (Denmark)

    Mucci, Lorelei A.; Hjelmborg, Jacob B.; Harris, Jennifer R.;

    2016-01-01

    (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. RESULTS: A total of 27,156 incident cancers were diagnosed in 23...... melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). CONCLUSIONS AND RELEVANCE: In this long-term follow-up study among...

  10. Immunolocalisation of members of the polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T) family is consistent with biologically relevant altered cell surface glycosylation in breast cancer

    DEFF Research Database (Denmark)

    Brooks, Susan A; Carter, Tracey M; Bennett, Eric P;

    2007-01-01

    An extensive family of UDP-N-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyltransferases (polypeptide N-acetylgalactosaminyltransferases, ppGalNAc-T's) catalyse the attachment of the first N-acetylgalactosamine (GalNAc) monosaccharide to the polypeptide at the initiation of O......,475). They stably synthesise varying levels, consistent with origin and phenotype, of aberrantly glycosylated glycoproteins featuring exposed, terminal GalNAc residues, including the cancer-associated Tn antigen, which, in numerous studies, have been associated with metastatic competence and poor cancer prognosis...... of the ppGalNAc-T family, ppGalNAc-T1, -T2, -T3, -T4 and -T6 in a range of breast cell lines. The cells were chosen to represent a range of phenotypes from 'normal'/benign (HMT 3,522), primary, non-metastatic breast cancer (BT 474), to aggressive, metastatic breast cancer (ZR75-1, T47D, MCF-7, DU 4...

  11. Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen; Christensen, Ib Jarle; Højen, Helle;

    2012-01-01

    Background and aim: Duodenal adenomatosis in FAP results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study is to present results of long-term duodenal surveillance and to evaluate the risk of...... (interquartile range 9-17). The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI 84-93), and of Spigelman stage IV 35% (95% CI 25-45). The Spigelman stage improved in 32 (12%), remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty patients (7%) had duodenal cancer at a median age of...

  12. Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen; Christensen, Ib Jarle; Højen, Helle;

    2012-01-01

    Background and aim:  Duodenal adenomatosis in FAP results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study is to present results of long-term duodenal surveillance and to evaluate the risk of...... (interquartile range 9-17). The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI 84-93), and of Spigelman stage IV 35% (95% CI 25-45). The Spigelman stage improved in 32 (12%), remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty patients (7%) had duodenal cancer at a median age of...

  13. 乳腺癌患者家庭沟通的研究进展%The research progress of family communication for breast cancer patients

    Institute of Scientific and Technical Information of China (English)

    张娜芹; 刘均娥

    2016-01-01

    Breast cancer is the most common cancer as well as the leading cause of cancer mortality among women worldwide. The diagnosis and treatment of cancer not only bring distress to patients but also have certain inlfuence on family communication. This article reviews the concept, measuring tools and research progress of family communication for breast cancer patients, in order to provide evidence for exploring particular family communication processes and working out better family communication intervention programs in future.%乳腺癌是女性最常见的恶性肿瘤。癌症的诊断和治疗不仅给患者带来痛苦,对家庭沟通也会造成一定影响。本文从家庭沟通的概念、测量工具及研究现状等方面对乳腺癌患者家庭沟通的研究进展进行综述,旨在为今后探究具体的家庭沟通过程、制定良好的家庭沟通干预方案提供依据。

  14. Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

    Directory of Open Access Journals (Sweden)

    Fleming Jodie M

    2012-06-01

    Full Text Available Abstract Background Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. Methods The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H2O2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Results Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Conclusions Our data opens new possibilities for hornerin and its

  15. Improving calculation, interpretation and communication of familial colorectal cancer risk: protocol for a randomized controlled trial.

    NARCIS (Netherlands)

    Dekker, N.; Hermens, R.P.M.G.; Elwyn, G.; Weijden, G.D.E.M. van der; Nagengast, F.M.; Duijvendijk, P. van; Salemink, S.; Adang, E.M.M.; Krieken, J.H.J.M. van; Ligtenberg, M.J.L.; Hoogerbrugge-van der Linden, N.

    2010-01-01

    BACKGROUND: Individuals with multiple relatives with colorectal cancer (CRC) and/or a relative with early-onset CRC have an increased risk of developing CRC. They are eligible for preventive measures, such as surveillance by regular colonoscopy and/or genetic counselling. Currently, most at-risk ind

  16. Genetic Counseling for Hereditary Cancer: A Pilot Study on Experiences of Patients and Family Members.

    Science.gov (United States)

    Bleiker, E. M. A.; Aaronson, N. K.; Menko, F. H.; Hahn, D. E. E.; van Asperen, C. J.; Rutgers, E. J. T.; ten Kate, L. P.; Leschot, N. J.

    1997-01-01

    Individuals who received genetic counseling for cancer (N=36) provided feedback on the quality of services and identified areas for improvement. Reasons for counseling and need for psychosocial support are also considered. Generally high levels of satisfaction with care provided were found. Four areas for improvement are identified and discussed.…

  17. Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms

    DEFF Research Database (Denmark)

    Rohde, Mikkel; Daugaard, Mads; Jensen, Mette Hartvig;

    2005-01-01

    Whereas the stress-inducible heat-shock protein 70 (Hsp70) has gained plenty of attention as a putative target for tumor therapy, little is known about the role of other Hsp70 proteins in cancer. Here we present the first thorough analysis of the expression and function of the cytosolic Hsp70...

  18. The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

    Science.gov (United States)

    Paolino, Magdalena; Penninger, Josef M.

    2016-01-01

    The TAM receptor protein tyrosine kinases—Tyro3, Axl, and Mer—are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy. PMID:27775650

  19. Apoptosis in haematological cancer : regulation by mitochondria, the BCL-2 family and IAPs

    NARCIS (Netherlands)

    Graaf, Aniek Odorica de

    2006-01-01

    This thesis describes a number of studies that investigated several aspects of apoptosis in lymphoid malignancies. Resistance to apoptosis is an important asset of cancer cells, which allows them to evade cell death signals instigated by the changes they undergo during transformation, such as genet

  20. The newcomer in the integrin family: Integrin a9 in biology and cancer

    DEFF Research Database (Denmark)

    Høye, Anette Melissa; Couchman, John Robert; Wewer, Ulla M.;

    2012-01-01

    Integrins are heterodimeric transmembrane receptors regulating cell-cell and cell-extracellular matrix interactions. Of the 24 integrin heterodimers identified in humans, a9ß1 integrin is one of the least studied. a9, together with a4, comprise a more recent evolutionary sub-family of integrins t...

  1. After BRCA1 and BRCA2-what next? Multifactorial segregation analyses of three-generation, population-based Australian families affected by female breast cancer.

    Science.gov (United States)

    Cui, J; Antoniou, A C; Dite, G S; Southey, M C; Venter, D J; Easton, D F; Giles, G G; McCredie, M R; Hopper, J L

    2001-02-01

    Mutations in BRCA1 and BRCA2 that cause a dominantly inherited high risk of female breast cancer seem to explain only a small proportion of the aggregation of the disease. To study the possible additional genetic components, we conducted single-locus and two-locus segregation analyses, with and without a polygenic background, using three-generation families ascertained through 858 women with breast cancer diagnosed at age Australia. Extensive testing for deleterious mutations in BRCA1 and BRCA2, to date, has identified 34 carriers. Our analysis suggested that, after other possible unmeasured familial factors are adjusted for and the known BRCA1 and BRCA2 mutation carriers are excluded, there appears to be a residual dominantly inherited risk of female breast cancer in addition to that derived from mutations in BRCA1 and BRCA2. This study also suggests that there is a substantial recessively inherited risk of early-onset breast cancer. According to the best-fitting model, after excluding known carriers of mutations in BRCA1 and BRCA2, about 1/250 (95% confidence interval [CI] 1/500 to 1/125) women have a recessive risk of 86% (95% CI 69%-100%) by age 50 years and of almost 100% by age 60 years. Possible reasons that our study has implicated a novel strong recessive effect include our inclusion of data on lineal aunts and grandmothers, study of families ascertained through women with early-onset breast cancer, allowance for multiple familial factors in the analysis, and removal of families for whom the cause (i.e., BRCA1 or BRCA2) is known. Our findings may have implications for attempts to identify new breast cancer-susceptibility genes. PMID:11133358

  2. Prevalence and Associated Factors of Anxiety and Depressive Symptoms Among Bereaved Family Members of Cancer Patients in Korea: A Nation-Wide Cross-Sectional Study.

    Science.gov (United States)

    Jho, Hyun Jung; Choi, Jin Young; Kwak, Kiu Sang; Chang, Yoon Jung; Ahn, Eun Mi; Park, Eun Jung; Paek, Soo Jin; Kim, Kyoung Mee; Kim, Soo Hyun

    2016-05-01

    Bereaved family members of cancer patient are at risk of having psychological problems such as anxiety and depression. However, prevalence and associated factors of anxiety and depressive symptoms among this population have not been explored in Korea.We conducted a nation-wide cross-sectional questionnaire survey of 3522 bereaved family members of cancer patients who died at 44 hospice palliative care unit (HPCU) in Korea in 2012. The questionnaire comprised the Hospital Anxiety and Depression Scale (HADS) and Good Death Inventory (GDI). Deceased patient's age, sex, primary site of cancer, duration of stay at HPCU, awareness of terminal status, bereaved family member's age, sex, and relation to the deceased were collected from Korean Terminal Cancer Patients Information System.1121 returned questionnaires were analyzed (response rate, 31.8%). Using a cut-off value of 8 for HADS subscale, the prevalence of anxiety and depressive symptoms was 48.0% and 57.6%, respectively. Mean scores for HADS-A and HADS-D were 7.88 ± 4.87 and 8.91 ± 4.82, respectively. Among the bereaved, older age, being a spouse to the deceased, family members of younger patient, and negative score for a few GDI items were significantly associated with an increased risk of having anxiety or depressive symptoms in the multivariate logistic analysis.In conclusion, we noted the high prevalence of anxiety and depressive symptoms among the bereaved of cancer patients and identified associated factors for these psychological morbidities. Systematic efforts are needed to improve the mental health of the bereaved family members of cancer patients. PMID:27258497

  3. Implications of conflicting definitions of probability to health risk communication: a case study of familial cancer and genetic counselling.

    Science.gov (United States)

    O'Doherty, Kieran C

    2007-02-01

    The question of what probability actually is has long been debated in philosophy and statistics. Although the concept of probability is fundamental to many applications in the health sciences, these debates are generally not well known to health professionals. This paper begins with an outline of some of the different interpretations of probability. Examples are provided of how each interpretation manifests in clinical practice. The discipline of genetic counselling (familial cancer) is used to ground the discussion. In the second part of the paper, some of the implications that different interpretations of probability may have in practice are examined. The main purpose of the paper is to draw attention to the fact that there is much contention as to the nature of the concept of probability. In practice, this creates the potential for ambiguity and confusion. This paper constitutes a call for deeper engagement with the ways in which probability and risk are understood in health research and practice.

  4. Bombesin family receptor and ligand gene expression in human colorectal cancer and normal mucosa

    OpenAIRE

    Chave, H S; Gough, A C; Palmer, K.; Preston, S. R.; Primrose, J N

    1999-01-01

    Bombesin-like peptides and their receptors are widely distributed throughout the gut and are potential mitogens for a number of gastrointestinal (GI) cancers. We have analysed the expression of bombesin-like peptides and their receptor subtypes in normal and neoplastic colorectal tissue. Expression was analysed by reverse transcription polymerase chain reaction (RT-PCR) using receptor and ligand subtype-specific primers and then expression localized by in situ hybridization (ISH) with ribopro...

  5. Comparison of individuals opting for BRCA1/2 or HNPCC genetic susceptibility testing with regard to coping, illness perceptions, illness experiences, family system characteristics and hereditary cancer distress

    NARCIS (Netherlands)

    van Oostrom, Iris; Meijers-Heijboer, Hanne; Duivenvoorden, Hugo J.; Brocker-Vriends, Annette H. J. T.; van Asperen, Christi J.; Sijmons, Rolf H.; Seynaeve, Caroline; Van Gool, Arthur R.; Klijn, Jan G. M.; Tibben, Aad

    2007-01-01

    Objective: To study differences between individuals opting for genetic cancer susceptibility testing of a known familial BRCA1/2 and HNPCC related germline mutation. Methods: Coping, illness perceptions, experiences with cancer in relatives and family system characteristics were assessed in 271 appl

  6. The ADAMs family of proteases as targets for the treatment of cancer.

    Science.gov (United States)

    Mullooly, Maeve; McGowan, Patricia M; Crown, John; Duffy, Michael J

    2016-08-01

    The ADAMs (a disintegrin and metalloproteases) are transmembrane multidomain proteins implicated in multiple biological processes including proteolysis, cell adhesion, cell fusion, cell proliferation and cell migration. Of these varied activities, the best studied is their role in proteolysis. However, of the 22 ADAMs believed to be functional in humans, only approximately a half possess matrix metalloproteinase (MMP)-like protease activity. In contrast to MMPs which are mostly implicated in the degradation of extracellular matrix proteins, the main ADAM substrates are the ectodomains of type I and type II transmembrane proteins. These include growth factor/cytokine precursors, growth factor/cytokine receptors and adhesion proteins. Recently, several different ADAMs, especially ADAM17, have been shown to play a role in the development and progression of multiple cancer types. Consistent with this role in cancer, targeting ADAM17 with either low molecular weight inhibitors or monoclonal antibodies was shown to have anti-cancer activity in multiple preclinical systems. Although early phase clinical trials have shown no serious side effects with a dual ADAM10/17 low molecular weight inhibitor, the consequences of long-term treatment with these agents is unknown. Furthermore, efficacy in clinical trials remains to be shown.

  7. The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer.

    Science.gov (United States)

    Graham, Douglas K; DeRyckere, Deborah; Davies, Kurtis D; Earp, H Shelton

    2014-12-01

    The TYRO3, AXL (also known as UFO) and MERTK (TAM) family of receptor tyrosine kinases (RTKs) are aberrantly expressed in multiple haematological and epithelial malignancies. Rather than functioning as oncogenic drivers, their induction in tumour cells predominately promotes survival, chemoresistance and motility. The unique mode of maximal activation of this RTK family requires an extracellular lipid–protein complex. For example, the protein ligand, growth arrest-specific protein 6 (GAS6), binds to phosphatidylserine (PtdSer) that is externalized on apoptotic cell membranes, which activates MERTK on macrophages. This triggers engulfment of apoptotic material and subsequent anti-inflammatory macrophage polarization. In tumours, autocrine and paracrine ligands and apoptotic cells are abundant, which provide a survival signal to the tumour cell and favour an anti-inflammatory, immunosuppressive microenvironment. Thus, TAM kinase inhibition could stimulate antitumour immunity, reduce tumour cell survival, enhance chemosensitivity and diminish metastatic potential. PMID:25568918

  8. The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer.

    Science.gov (United States)

    Graham, Douglas K; DeRyckere, Deborah; Davies, Kurtis D; Earp, H Shelton

    2014-12-01

    The TYRO3, AXL (also known as UFO) and MERTK (TAM) family of receptor tyrosine kinases (RTKs) are aberrantly expressed in multiple haematological and epithelial malignancies. Rather than functioning as oncogenic drivers, their induction in tumour cells predominately promotes survival, chemoresistance and motility. The unique mode of maximal activation of this RTK family requires an extracellular lipid–protein complex. For example, the protein ligand, growth arrest-specific protein 6 (GAS6), binds to phosphatidylserine (PtdSer) that is externalized on apoptotic cell membranes, which activates MERTK on macrophages. This triggers engulfment of apoptotic material and subsequent anti-inflammatory macrophage polarization. In tumours, autocrine and paracrine ligands and apoptotic cells are abundant, which provide a survival signal to the tumour cell and favour an anti-inflammatory, immunosuppressive microenvironment. Thus, TAM kinase inhibition could stimulate antitumour immunity, reduce tumour cell survival, enhance chemosensitivity and diminish metastatic potential.

  9. Predictors of Posttraumatic Stress Symptoms Among Adolescent and Young Adult Survivors of Childhood Cancer: Importance of Monitoring Survivors' Experiences of Family Functioning.

    Science.gov (United States)

    Kamibeppu, Kiyoko; Murayama, Shiho; Ozono, Shuichi; Sakamoto, Naoko; Iwai, Tsuyako; Asami, Keiko; Maeda, Naoko; Inada, Hiroko; Kakee, Naoko; Okamura, Jun; Horibe, Keizo; Ishida, Yasushi

    2015-11-01

    The purpose of this study was to identify factors associated with posttraumatic stress symptoms (PTSS) among Japanese long-term childhood cancer survivors (CCSs). Subjects comprised 185 adolescent and young adult (AYA) CCSs who completed anonymous self-report questionnaires. Attending physicians also completed an anonymous disease/treatment data sheet. Mean age of survivors was approximately 8 years at diagnosis and 23 years at participation. Multiple regression analysis showed that family functioning, satisfaction with social support, being female, and interactions between family functioning and gender and age at the time of diagnosis were associated with PTSS among survivors. This study revealed family functioning as the most predictive factor of PTSS among AYA CCSs in Japan. Even when the survivor may have unchangeable risk factors, family functioning can potentially moderate the effects on PTSS. Thus, it is crucial for health professionals to carefully monitor and attend to survivors' experiences of family functioning to mitigate PTSS. PMID:26442952

  10. 家族性胃癌遗传学研究进展%Genetic progression of familial gastric cancer

    Institute of Scientific and Technical Information of China (English)

    甘露; 王杰军

    2011-01-01

    遗传性弥漫型胃癌与钙黏蛋白基因的种系突变有关,约占家族性胃癌病例的1/3。其他2/3不符合遗传性弥漫型胃癌诊断标准的家族性胃癌依然缺乏明确的分子诊断依据。目前根据钙黏蛋白基因预测情况预防性切除相关家族性胃癌,只在一部分遗传性弥漫型胃癌中有临床意义。%The hereditary diffuse gastric cancer (HDGC) is associated with CDHI (E-cadherin gene)germline mutations, and accounts for about one-third of the familial gastric cancer (FGC) cases. The other two thirds FGC cases which are not fit the diagnosis standard of HDGC remain lack of clear molecular diagnosis basis. The current disposal of prophylactic gastrectomy in FGC according to E-cadherins genetic counseling, has clinical significance only in part of HDGC.

  11. Fear of death, mortality communication, and psychological distress among secular and religiously observant family caregivers of terminal cancer patients.

    Science.gov (United States)

    Bachner, Yaacov G; O'Rourke, Norm; Carmel, Sara

    2011-02-01

    Previous research suggests that caregivers and terminally ill patients face substantial difficulties discussing illness and death. Existing research, however, has focused primarily on the experience of patients. The current study compared responses as well as the relative strength of association between mortality comunication, fear of death, and psychological distress (i.e., depressive symptomatology, emotional exhaustion) among secular and religiously observant family caregivers of terminally ill cancer patients. A total of 236 participants were recruited over 18 months within the first year of caregiver bereavement. Retrospectively reported mortality communication was statistically greater among secular caregivers; in contrast, both fear of death and depressive symptoms were greater among the religiously observant. Path analyses subsequently revealed notable differences between groups. Among secular caregivers, a significant inverse relationship between mortality communication and the two indices of caregiver distress emerged. In contrast, the association between mortality communication and psychological distress among the religious was moderated by these caregivers' fear of death. The results of this study suggest that fear of death is a significant predictor of psychological distress among religiously observant caregivers of terminal cancer patients (i.e., fear of their own death as elicited by the caregiving role). Fostering morality communication between secular caregivers and patients would appear to be one means of reducing the likelihood of clinically significant psychological distress. This may be insufficient among religiously observant caregivers, however, for whom fear of death may first need to be redressed. PMID:24501834

  12. Testicular cancer

    Science.gov (United States)

    Testicular cancer is cancer that starts in the testicles, the male reproductive glands located in the scrotum. ... developing testicular cancer increases if he has: Abnormal testicle development Exposure to certain chemicals Family history of ...

  13. Stomach Cancer

    Science.gov (United States)

    ... with stomach acid and helps digest protein. Stomach cancer mostly affects older people - two-thirds of people ... Smoke cigarettes Have a family history of stomach cancer It is hard to diagnose stomach cancer in ...

  14. Janus kinases and Src family kinases in the regulation of EGF-induced vimentin expression in MDA-MB-468 breast cancer cells.

    Science.gov (United States)

    Stewart, Teneale A; Azimi, Iman; Brooks, Andrew J; Thompson, Erik W; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2016-07-01

    Epithelial-mesenchymal transition (EMT) is an important process associated with the metastasis of breast cancer cells. Members of the Janus kinases (JAKs) and Src family kinases (SFKs) are implicated in the regulation of an invasive phenotype in various cancer cell types. Using the pharmacological inhibitors JAK Inhibitor I (a pan-JAK inhibitor) and PP2 we investigated the role of the JAKs and SFKs, respectively, in the regulation of EMT markers in the MDA-MB-468 breast cancer cell line model of epidermal growth factor (EGF)-induced EMT. We identified selective inhibition of EGF induction of the mesenchymal marker vimentin by PP2 and JAK Inhibitor I. The effect of JAK Inhibitor I on vimentin protein induction occurred at a concentration lower than that required to significantly inhibit EGF-mediated signal transducer and activator of transcription 3 (STAT3)-phosphorylation, suggesting involvement of a STAT3-independent mechanism of EGF-induced vimentin regulation by JAKs. Despite our identification of a role for the JAK family in EGF-induced vimentin protein expression, siRNA-mediated silencing of each member of the JAK family was unable to phenocopy pharmacological inhibition, indicating potential redundancy among the JAK family members in this pathway. While SFKs and JAKs do not represent global regulators of the EMT phenotype, our findings have identified a role for members of these signaling pathways in the regulation of EGF-induced vimentin expression in the MDA-MB-468 breast cancer cell line. PMID:27163529

  15. The Family Living with Prostate Cancer - The Wife`s Perspective

    DEFF Research Database (Denmark)

    Bruun, Poul; Pedersen, Birthe D.; Osther, Palle;

    in three stages, namely a naïve analy­sis, followed by a more structured analysis, and concludes with critical interpretation and discussion. Results: The results of the analysis showed one main theme; coping with life and three sub-themes Aspects of loneliness Women experience different aspects...... of loneliness when their husband is diagnosed with incurable prostate cancer. A self-inflicted loneliness which can lead to isolation and over time to a state of complete prostration that makes it difficult to cope with life. A self-imposed loneliness which makes sense in the light of an obligation to care...

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to Cancer Self Image & Sexuality Day to Day Life Survivorship For Family & Friends Questions to Ask About Cancer Advanced Cancer ...

  17. A screen for germline mutations in the gene encoding CCCTC-binding factor (CTCF) in familial non-BRCA1/BRCA2 breast cancer

    International Nuclear Information System (INIS)

    The CCCTC-binding factor (CTCF), known as a versatile transcription factor and chromatin insulator and to be involved in X inactivation, has also been suggested to be a tumour suppressor on 16q. We investigated 153 patients with familial non-BRCA1/BRCA2 breast cancer for germline mutations in the CTCF gene. Mutation screening of CTCF was performed by denaturing high-performance liquid chromatography followed by cycle sequencing. We found two sequence variants, 240G→A in the 5' untranslated region and 1455C→T (S388S) in exon 4, in five familial breast cancer cases. Three of these five cases had both variants. Cases and controls showed the same prevalence for the two variants, which were found in linkage disequilibrium in most cases and controls. The present study suggests that germline mutations in CTCF are not important as a risk factor for breast cancer

  18. The impact of family history of breast cancer on knowledge, attitudes, and early detection practices of Mexican women along the Mexico-US border.

    Science.gov (United States)

    Bird, Yelena; Banegas, Matthew P; Moraros, John; King, Sasha; Prapasiri, Surasri; Thompson, Beti

    2011-10-01

    Rates of breast cancer (BC) have increased in Mexico, with the highest incidence and mortality rates observed in the northern Mexican states. This study aimed to describe the BC knowledge, attitudes and screening practices among Mexican women with and without a family history of BC residing along the Mexico-US border, and identify factors associated with screening behaviors. One hundred and twenty eight Mexican women aged 40 and older completed an interviewer-administered questionnaire on sociodemographic characteristics, knowledge, family history, and screening practices. There were no significant differences between Mexican women with and without a family history. Over 60% of women in both groups had never had a mammogram/breast ultrasound, and more than 50% had never obtained a clinical breast exam. Age, marital status, insurance, and breast cancer knowledge significantly influenced BC screening behaviors among Mexican women. Further research is needed to examine other key factors associated with screening utilization, in effort of improving BC rates.

  19. Whole exome sequencing suggests much of non-BRCA1/BRCA2 familial breast cancer is due to moderate and low penetrance susceptibility alleles.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Gracia-Aznarez

    Full Text Available The identification of the two most prevalent susceptibility genes in breast cancer, BRCA1 and BRCA2, was the beginning of a sustained effort to uncover new genes explaining the missing heritability in this disease. Today, additional high, moderate and low penetrance genes have been identified in breast cancer, such as P53, PTEN, STK11, PALB2 or ATM, globally accounting for around 35 percent of the familial cases. In the present study we used massively parallel sequencing to analyze 7 BRCA1/BRCA2 negative families, each having at least 6 affected women with breast cancer (between 6 and 10 diagnosed under the age of 60 across generations. After extensive filtering, Sanger sequencing validation and co-segregation studies, variants were prioritized through either control-population studies, including up to 750 healthy individuals, or case-control assays comprising approximately 5300 samples. As a result, a known moderate susceptibility indel variant (CHEK2 1100delC and a catalogue of 11 rare variants presenting signs of association with breast cancer were identified. All the affected genes are involved in important cellular mechanisms like DNA repair, cell proliferation and survival or cell cycle regulation. This study highlights the need to investigate the role of rare variants in familial cancer development by means of novel high throughput analysis strategies optimized for genetically heterogeneous scenarios. Even considering the intrinsic limitations of exome resequencing studies, our findings support the hypothesis that the majority of non-BRCA1/BRCA2 breast cancer families might be explained by the action of moderate and/or low penetrance susceptibility alleles.

  20. Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy

    Directory of Open Access Journals (Sweden)

    Batra Surinder K

    2011-08-01

    Full Text Available Abstract Curcumin has attracted great attention in the therapeutic arsenal in clinical oncology due to its chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against various types of aggressive and recurrent cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain cancer, melanoma and skin, lung, prostate, breast, ovarian, liver, gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates its anti-proliferative, anti-invasive and apoptotic effects on cancer cells, including cancer stem/progenitor cells and their progenies, through multiple molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the members of epidermal growth factor receptors (EGFR and erbB2, sonic hedgehog (SHH/GLIs and Wnt/β-catenin and downstream signaling elements such as Akt, nuclear factor-kappa B (NF-κB and signal transducers and activators of transcription (STATs. In counterbalance, the high metabolic instability and poor systemic bioavailability of curcumin limit its therapeutic efficacy in human. Of great therapeutic interest, the selective delivery of synthetic analogs or nanotechnology-based formulations of curcumin to tumors, alone or in combination with other anticancer drugs, may improve their chemopreventive and chemotherapeutic efficacies against cancer progression and relapse. Novel curcumin formulations may also be used to reverse drug resistance, eradicate the total cancer cell mass and improve the anticarcinogenic efficacy of the current anti-hormonal and chemotherapeutic treatments for patients with various aggressive and lethal cancers.

  1. Communication to pediatric cancer patients and their families: A cultural perspective

    Directory of Open Access Journals (Sweden)

    Tulika Seth

    2010-01-01

    Full Text Available Background: Communication is a key component of palliative care. The area of pediatric palliative care is emotionally distressing for families and healthcare providers. Inadequate communication can increase the stress and lead to mistrust or miscommunication. Materials and Methods: Reviewing the literature on communication between physicians and patients, we identified several barriers to communication such as paternalism in medicine, inadequate training in communication skills, knowledge of the grieving process, special issues related to care of children and cultural barriers. In order to fill the void in area of cultural communication, a study questionnaire was administered to consecutive families of children receiving chemotherapy at a large, north Indian referral hospital to elicit parental views on communication. Results: Most parents had a protective attitude and favored collusion, however, appreciated truthfulness in prognostication and counseling by physicians; though parents expressed dissatisfaction on timing and lack of prior information by counseling team. Conclusion: Training programs in communication skills should teach doctors how to elicit patients′ preferences for information. Systematic training programs with feedback can decrease physicians stress and burnout. More research for understanding a culturally appropriate communication framework is needed.

  2. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    Directory of Open Access Journals (Sweden)

    Gonzalez-Neira Anna

    2007-08-01

    Full Text Available Abstract Background The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel, with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion Our results show the power increase that SNPs can supply in linkage studies.

  3. MLH1 promoter germline-methylation in selected probands of Chinese hereditary non-polyposis colorectal cancer families

    Institute of Scientific and Technical Information of China (English)

    Heng-Hua Zhou; Shi-Yan Yan; Xiao-Yan Zhou; Xiang Du; Tai-Ming Zhang; Xu Cai; Yong-Ming Lu; San-Jun Cai; Da-Ren Shi

    2008-01-01

    AIM:To detect the MLH1 gene promoter germlinemethylation in probands of Chinese hereditary nonpolyposis colorectal cancer (HNPCC),and to evaluate the role of methylation in MLH1 gene promoter and molecular genetics in screening for HNPCC.METHODS:The promoter germline methylation of MLH1 gene was detected by methylation-specific PCR (MSP) in 18 probands from unrelated HNPCC families with high microsatellite-instability (MSI-H) phenotype but without germline mutations in MSH2,MLH1 and MSH6 genes.At the same time,6 kindreds were collected with microsatellite-stability (MSS) phenotype but without germline mutations in MSH2,MLH1 and MSH6 genes as controls.The results of MSP were confirmed by clone sequencing.To ensure the reliability of the results,family H65 with nonsense germline mutation at c.2228C>A in MSH2 gene was used as the negative control and the cell line sw48 was used as the known positive control along with water as the blank control.Immunochemical staining of MLH1 protein was performed with Envision two-step method in those patients with aberrant methylation to judge whether the status of MLH1 gene methylation affects the expression of MLH1 protein.RESULTS:Five probands with MLH1 gene promoter methylation were detected in 18 Chinese HNPCC families with MSI-H phenotype but without germline mutations in MSH2,MLH1 and MSH6 genes.Two of the five probands from families H10 and H29 displayed exhaustive-methylation,fulfilling the Japanese criteria (JC) and the Amsterdam criteria (AC),respectively.The other 3 probands presented part-methylation fulfilling the AC.Of the 13 probands with unmethylation phenotype,8 fulfilled the JC and the Bethesda guidelines (BG),5 fulfilled the AC.The rate of aberrant methylation in MLH1 gene in the AC group (22.2%,4/18) was higher than that in the JC/BG groups (5.6%,1/18) in all HNPCC families with MSI-H phenotype but without germline mutations in MSH2,MLH1 and MSH6 genes.However,no proband with methylation in MLH1 gene was found

  4. Some further results on incorporating risk factor information in assessing the dependence between paired failure times arising from case-control family studies: an application to prostate cancer.

    Science.gov (United States)

    Hsu, Li; Prentice, Ross L; Stanford, Janet L

    2002-03-30

    In a typical case-control family study, detailed risk factor information is often collected on cases and controls, but not on their relatives for reasons of cost and logistical difficulty in locating the relatives. The impact of missing risk factor information for relatives on estimation of the strength of dependence between the disease risk of pairs of relatives is largely unknown. In this paper, we extend our earlier work on estimating the dependence of ages at onset between paired relatives from case-control family data to include covariates on cases and controls, and possibly relatives. Using population-based case-control families as our basic data structure, we study the effect of missing covariates for relatives and/or cases and controls on the bias of certain dependence parameter estimators via a simulation study. Finally we illustrate various analyses using a case-control family study of early onset prostate cancer. PMID:11870822

  5. Effects of Rational-Emotive Hospice Care Therapy on Problematic Assumptions, Death Anxiety, and Psychological Distress in a Sample of Cancer Patients and Their Family Caregivers in Nigeria

    Directory of Open Access Journals (Sweden)

    Kay Chinonyelum Nwamaka Onyechi

    2016-09-01

    Full Text Available This study was a preliminary investigation that aimed to examine the effects of rational emotive hospice care therapy (REHCT on problematic assumptions, death anxiety, and psychological distress in a sample of cancer patients and their family caregivers in Nigeria. The study adopted a pre-posttest randomized control group design. Participants were community-dwelling cancer patients (n = 32 and their family caregivers (n = 52. The treatment process consisted of 10 weeks of full intervention and 4 weeks of follow-up meetings that marked the end of intervention. The study used repeated-measures analysis of variance for data analysis. The findings revealed significant effects of a REHCT intervention program on problematic assumptions, death anxiety, and psychological distress reduction among the cancer patients and their family caregivers at the end of the intervention. The improvements were also maintained at follow-up meetings in the treatment group compared with the control group who received the usual care and conventional counseling. The researchers have been able to show that REHCT intervention is more effective than a control therapy for cancer patients’ care, education, and counseling in the Nigerian context.

  6. Effects of Rational-Emotive Hospice Care Therapy on Problematic Assumptions, Death Anxiety, and Psychological Distress in a Sample of Cancer Patients and Their Family Caregivers in Nigeria

    Science.gov (United States)

    Onyechi, Kay Chinonyelum Nwamaka; Onuigbo, Liziana N.; Eseadi, Chiedu; Ikechukwu-Ilomuanya, Amaka B.; Nwaubani, Okechukwu Onyinye; Umoke, Prince C.I.; Agu, Fedinand U.; Otu, Mkpoikanke Sunday; Utoh-Ofong, Anthonia N.

    2016-01-01

    This study was a preliminary investigation that aimed to examine the effects of rational emotive hospice care therapy (REHCT) on problematic assumptions, death anxiety, and psychological distress in a sample of cancer patients and their family caregivers in Nigeria. The study adopted a pre-posttest randomized control group design. Participants were community-dwelling cancer patients (n = 32) and their family caregivers (n = 52). The treatment process consisted of 10 weeks of full intervention and 4 weeks of follow-up meetings that marked the end of intervention. The study used repeated-measures analysis of variance for data analysis. The findings revealed significant effects of a REHCT intervention program on problematic assumptions, death anxiety, and psychological distress reduction among the cancer patients and their family caregivers at the end of the intervention. The improvements were also maintained at follow-up meetings in the treatment group compared with the control group who received the usual care and conventional counseling. The researchers have been able to show that REHCT intervention is more effective than a control therapy for cancer patients’ care, education, and counseling in the Nigerian context. PMID:27657099

  7. Do Breast Cancer Patients Tested in the Oncology Care Setting Share BRCA Mutation Results with Family Members and Health Care Providers?

    Directory of Open Access Journals (Sweden)

    Susan T. Vadaparampil

    2012-01-01

    Full Text Available BRCA genetic test results provide important information to manage cancer risk for patients and their families. Little is known on the communication of genetic test results by mutation status with family members and physicians in the oncology care setting. As part of a longitudinal study evaluating the impact of genetic counseling and testing among recently diagnosed breast cancer patients, we collected patients' self-reported patterns of disclosure. Descriptive statistics characterized the sample and determined the prevalence of disclosure of BRCA test results to family members and physicians. Of 100 patients who completed the baseline and the 6-month followup survey, 77 reported pursuing testing. The majority shared test results with female first-degree relatives; fewer did with males. Participants were more likely to share results with oncologists compared to surgeons, primary care physicians, or other specialty physicians. These findings suggest that while breast cancer patients may communicate results to at-risk female family members and their medical oncologist, they may need education and support to facilitate communication to other first-degree relatives and providers.

  8. Lack of germline A339V mutation in thyroid transcription factor-1 (TITF-1/NKX2.1 gene in familial papillary thyroid cancer

    Directory of Open Access Journals (Sweden)

    Cantara Silvia

    2010-08-01

    Full Text Available Abstract Thyroid cancer may have a familial predisposition but a specific germline alteration responsible for the disease has not been discovered yet. We have shown that familial papillary thyroid cancer (FPTC patients have an imbalance in telomere-telomerase complex with short telomeres and increased telomerase activity. A germline mutation (A339V in thyroid transcription factor-1 has been described in patients with multinodular goiter and papillary thyroid cancer. In this report, the presence of the A339V mutation and the telomere length has been studied in FPTC patients and unaffected family members. All samples analyzed displayed a pattern typical of the homozygous wild type revealing the absence of the A339V mutation. Shortening of telomeres was confirmed in all patients. We concluded that the A339V mutation in thyroid transcription factor-1 (TITF-1/NKX2.1 is not correlated with the familial form of PTC, even when the tumor was in the context of multinodular goiter.

  9. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Self Image & Sexuality Day-to-Day Life For Family & Friends Survivorship Questions to Ask About Cancer Research ... Image & Sexuality Day to Day Life Survivorship For Family & Friends Questions to Ask About Cancer Advanced Cancer ...

  10. Close relatives find meaning to cope with cancer diagnosis and treatment of family members.

    Science.gov (United States)

    Feyh, Janelle M; Levine, Ellen G; Clay, Karine

    2012-12-01

    Pediatric palliative care has recently become a priority in the health care field and is implemented at the time of diagnosis rather than days or weeks before the child's death. Social constructivism theory in which humans generate meaning from their experiences was utilized as a general framework to determine the impact of pediatric palliative care on close relatives. The purpose of this grounded theory study was to generate a substantive theory that explains how close relatives such as grandparents, aunts, and uncles of a child with cancer experience palliative care. The participants of the study included close relatives of children in palliative care. Semistructured interviews and journaling were used to collect data. Initial, focused, and axial coding procedures were used to manage the data and a content analysis of the textual data was performed. Findings from the data suggested a process of finding meaning which helps close relatives to let go of what they cannot control while holding on to what they can control. Social change implications of this study may include improving health care programming for close relatives utilizing supportive-expressive measures. This programming may promote mental health of the close relatives who will learn to deal with their adjustment difficulties and improve their coping skills. PMID:22363041

  11. 家族性多原发癌3例临床分析%Reports and Analysis of 3 Multiple Primary Cancers Cases from a Family

    Institute of Scientific and Technical Information of China (English)

    李志鹏; 陈方进

    2012-01-01

    目的 分析多原发癌(MPC)在家族遗传方面的因素,以提高对多原发癌的诊治及预防.方法 结合国内外相关文献,对一家族(无近亲结婚)三代中癌症患者的临床资料进行分析.结果 该家族三代中7例为癌症患者,男性2例,女性5例,年龄39~78岁,平均55岁,其中3例女性发生异时性MPC,每次相隔3~5年.大肠癌4例(57%);子宫癌5例(71%);膀胱癌、肺癌各1例(14%).该家族中MPC患者占总家族患癌成员的43%(3/7).结论 该家族中MPC患者5年生存率较各单发恶性肿瘤者高.了解患者的家族病史,早期诊断,可显著延长患者生存期.%Objective To analyze the genetic factors of multiple primary cancers so as to improve the diagnosis and prevention of multiple primary cancers. Methods Clinical data from a family with multiple primary cancers were analyzed, and the related literatures were reviewed. Results The family had a total of 7 cancer sufferers, including 2 males and 5 females. The age was from 39 to 78 years,with an average 55 years old. Three women had metachronous MPC,with an intervals of 3 to 5 years. There were 4 ( 57% ) colorectal cancer,5 ( 71% ) uterine cancer,1 ( 14% ) bladder cancer and 1 lung cancer. 3 of the 7 ( 43% ) cancer suffers had MPC. Conclusion The five-year survival in patients with MPC is higher than that in patients with a single type of cancer. Understanding the patient's family and medical history, early diagnosis and active treatment can significantly improve survival.

  12. FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor

    Science.gov (United States)

    Peterlongo, Paolo; Catucci, Irene; Colombo, Mara; Caleca, Laura; Mucaki, Eliseos; Bogliolo, Massimo; Marin, Maria; Damiola, Francesca; Bernard, Loris; Pensotti, Valeria; Volorio, Sara; Dall'Olio, Valentina; Meindl, Alfons; Bartram, Claus; Sutter, Christian; Surowy, Harald; Sornin, Valérie; Dondon, Marie-Gabrielle; Eon-Marchais, Séverine; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Sinilnikova, Olga M.; Mitchell, Gillian; James, Paul A.; Thompson, Ella; Marchetti, Marina; Verzeroli, Cristina; Tartari, Carmen; Capone, Gabriele Lorenzo; Putignano, Anna Laura; Genuardi, Maurizio; Medici, Veronica; Marchi, Isabella; Federico, Massimo; Tognazzo, Silvia; Matricardi, Laura; Agata, Simona; Dolcetti, Riccardo; Puppa, Lara Della; Cini, Giulia; Gismondi, Viviana; Viassolo, Valeria; Perfumo, Chiara; Mencarelli, Maria Antonietta; Baldassarri, Margherita; Peissel, Bernard; Roversi, Gaia; Silvestri, Valentina; Rizzolo, Piera; Spina, Francesca; Vivanet, Caterina; Tibiletti, Maria Grazia; Caligo, Maria Adelaide; Gambino, Gaetana; Tommasi, Stefania; Pilato, Brunella; Tondini, Carlo; Corna, Chiara; Bonanni, Bernardo; Barile, Monica; Osorio, Ana; Benitez, Javier; Balestrino, Luisa; Ottini, Laura; Manoukian, Siranoush; Pierotti, Marco A.; Renieri, Alessandra; Varesco, Liliana; Couch, Fergus J.; Wang, Xianshu; Devilee, Peter; Hilbers, Florentine S.; van Asperen, Christi J.; Viel, Alessandra; Montagna, Marco; Cortesi, Laura; Diez, Orland; Balmaña, Judith; Hauke, Jan; Schmutzler, Rita K.; Papi, Laura; Pujana, Miguel Angel; Lázaro, Conxi; Falanga, Anna; Offit, Kenneth; Vijai, Joseph; Campbell, Ian; Burwinkel, Barbara; Kvist, Anders; Ehrencrona, Hans; Mazoyer, Sylvie; Pizzamiglio, Sara; Verderio, Paolo; Surralles, Jordi; Rogan, Peter K.; Radice, Paolo

    2015-01-01

    Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28–12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04–12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09–13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer. PMID:26130695

  13. FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.

    Science.gov (United States)

    Peterlongo, Paolo; Catucci, Irene; Colombo, Mara; Caleca, Laura; Mucaki, Eliseos; Bogliolo, Massimo; Marin, Maria; Damiola, Francesca; Bernard, Loris; Pensotti, Valeria; Volorio, Sara; Dall'Olio, Valentina; Meindl, Alfons; Bartram, Claus; Sutter, Christian; Surowy, Harald; Sornin, Valérie; Dondon, Marie-Gabrielle; Eon-Marchais, Séverine; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Sinilnikova, Olga M; Mitchell, Gillian; James, Paul A; Thompson, Ella; Marchetti, Marina; Verzeroli, Cristina; Tartari, Carmen; Capone, Gabriele Lorenzo; Putignano, Anna Laura; Genuardi, Maurizio; Medici, Veronica; Marchi, Isabella; Federico, Massimo; Tognazzo, Silvia; Matricardi, Laura; Agata, Simona; Dolcetti, Riccardo; Della Puppa, Lara; Cini, Giulia; Gismondi, Viviana; Viassolo, Valeria; Perfumo, Chiara; Mencarelli, Maria Antonietta; Baldassarri, Margherita; Peissel, Bernard; Roversi, Gaia; Silvestri, Valentina; Rizzolo, Piera; Spina, Francesca; Vivanet, Caterina; Tibiletti, Maria Grazia; Caligo, Maria Adelaide; Gambino, Gaetana; Tommasi, Stefania; Pilato, Brunella; Tondini, Carlo; Corna, Chiara; Bonanni, Bernardo; Barile, Monica; Osorio, Ana; Benitez, Javier; Balestrino, Luisa; Ottini, Laura; Manoukian, Siranoush; Pierotti, Marco A; Renieri, Alessandra; Varesco, Liliana; Couch, Fergus J; Wang, Xianshu; Devilee, Peter; Hilbers, Florentine S; van Asperen, Christi J; Viel, Alessandra; Montagna, Marco; Cortesi, Laura; Diez, Orland; Balmaña, Judith; Hauke, Jan; Schmutzler, Rita K; Papi, Laura; Pujana, Miguel Angel; Lázaro, Conxi; Falanga, Anna; Offit, Kenneth; Vijai, Joseph; Campbell, Ian; Burwinkel, Barbara; Kvist, Anders; Ehrencrona, Hans; Mazoyer, Sylvie; Pizzamiglio, Sara; Verderio, Paolo; Surralles, Jordi; Rogan, Peter K; Radice, Paolo

    2015-09-15

    Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer. PMID:26130695

  14. A survey of genetic counselors about the needs of 18-25 year olds from families with hereditary breast and ovarian cancer syndrome.

    Science.gov (United States)

    Werner-Lin, Allison; Ratner, Rachel; Hoskins, Lindsey M; Lieber, Caroline

    2015-02-01

    As a result of modern treatments, the life of women who test positive for BRCA mutations may be plotted along the arc of preventive medicine rather than the slope of diagnostics. Despite evidence supporting the benefits of risk reduction, protocols for early detection and prevention among women from families affected by hereditary breast and ovarian cancer (HBOC) are not yet proven, and clinical trials have not been undertaken for patients aged 18 to 25. The absence of psychosocial data may leave genetic counselors without uniform guidance on how to manage the care of these patients. This project sought to investigate perspectives on counseling 18-25 year-old patients from families with hereditary cancer syndromes, with specific emphasis on HBOC, given their unique developmental, familial, and medical challenges. Certified genetic counselors were recruited through the NSGC's Cancer Genetics Special Interest Group listserv. Researchers constructed an online survey which included 41 items and elicited information about: counselor demographics, training, and practice settings; approaches to cancer risk assessment; and common challenges in work with 18- to 25-year-old patients. The survey was also informed by previous work by researchers with 18 to 25-year-olds with BRCA gene mutations. Eighty-six surveys were completed. Researchers used a combination of grounded theory and content analysis for open-ended responses, supported and triangulated with statistical analysis to maximize the interpretation of data. Genetic counselors who responded to this survey experience 18-25 year old patients presenting for cancer risk assessment differently than older patients, and some reported adapting their counseling style to address these differences. Respondents differed in the extent to which they felt well-versed in the developmental needs of patients in this age group. Respondents aged 39 and under reported feeling familiar with this stage in life, having more recently

  15. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jansen-van der Weide, Marijke C. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands); Greuter, Marcel J.W.; Pijnappel, Ruud M. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); Jansen, Liesbeth [University Medical Center Groningen, University of Groningen, Department of Surgery, Groningen (Netherlands); Oosterwijk, Jan C. [University Medical Center Groningen, University of Groningen, Department of Clinical Genetics, Groningen (Netherlands); Bock, Geertruida H. de [University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands)

    2010-11-15

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of {>=}5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. (orig.)

  16. Despite shared susceptibility loci, esophageal squamous cell carcinoma embraces more familial cancer than gastric cardia adenocarcinoma in the Taihang Mountains high-risk region of northern central China

    Institute of Scientific and Technical Information of China (English)

    WEN Deng-gui; YANG Yi; WEN Xiao-duo; SHAN Bao-en

    2013-01-01

    Background In China,esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci,but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal.Methods The percent of cases with a positive family history,median onset age,rate of multiple primary cancer,and male/female ratio associated with upper,middle,lower third ESCC and GCA were compared to reveal the proportion of familial cancer.The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University.Results A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases,e.g.with 42% of the males and 59% of the females.For upper,middle,lower third ESCC and GCA,the percent of cases with a positive family history decreased by 38.5%,26.3%,26.5%,and 11.2% in males (P <0.000) and 25.0%,22.3%,23.9%,and 9.8% in females (P <0.0001).Median onset age increased from 49,52,55,to 56 years old in males and from 50,53,55,to 56 years old in females (both P <0.0001) for upper,middle,lower third ESCC and GCA.Male/female ratio increased from 2.2,2.1,2.2,to 6.2:1 for upper,middle,lower third ESCC and GCA (P<0.0001).For upper,middle,lower third ESCC and GCA,the percent of multiple primary cancers decreased from 21.2%,2.3%,2.2%,to 1.5% in males and from 14.3%,2.4%,3.4%,to 3.1% in females.The preponderance of males,smoking,drinking,or onset-age ≥50 years was significantly higher in GCA than in ESCC,and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA,but not in ESCC,suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist.Conclusions The proportion of familial cancer in upper gastrointestinal

  17. Patterns of Cancer Genetic Testing: A Randomized Survey of Oregon Clinicians

    Directory of Open Access Journals (Sweden)

    Summer L. Cox

    2012-01-01

    Full Text Available Introduction. Appropriate use of genetic tests for population-based cancer screening, diagnosis of inherited cancers, and guidance of cancer treatment can improve health outcomes. We investigated clinicians’ use and knowledge of eight breast, ovarian, and colorectal cancer genetic tests. Methods. We conducted a randomized survey of 2,191 Oregon providers, asking about their experience with fecal DNA, OncoVue, BRCA, MMR, CYP2D6, tumor gene expression profiling, UGT1A1, and KRAS. Results. Clinicians reported low confidence in their knowledge of medical genetics; most confident were OB-GYNs and specialists. Clinicians were more likely to have ordered/recommended BRCA and MMR than the other tests, and OB-GYNs were twice as likely to have ordered/recommended BRCA testing than primary care providers. Less than 10% of providers ordered/recommended OncoVue, fecal DNA, CYP2D6, or UGT1A1; less than 30% ordered/recommended tumor gene expression profiles or KRAS. The most common reason for not ordering/recommending these tests was lack of familiarity. Conclusions. Use of appropriate, evidence-based testing can help reduce incidence and mortality of certain cancers, but these tests need to be better integrated into clinical practice. Continued evaluation of emerging technologies, dissemination of findings, and an increase in provider confidence and knowledge are necessary to achieve this end.

  18. A new molecular signature method for prediction of driver cancer pathways from transcriptional data.

    Science.gov (United States)

    Rykunov, Dmitry; Beckmann, Noam D; Li, Hui; Uzilov, Andrew; Schadt, Eric E; Reva, Boris

    2016-06-20

    Assigning cancer patients to the most effective treatments requires an understanding of the molecular basis of their disease. While DNA-based molecular profiling approaches have flourished over the past several years to transform our understanding of driver pathways across a broad range of tumors, a systematic characterization of key driver pathways based on RNA data has not been undertaken. Here we introduce a new approach for predicting the status of driver cancer pathways based on signature functions derived from RNA sequencing data. To identify the driver cancer pathways of interest, we mined DNA variant data from TCGA and nominated driver alterations in seven major cancer pathways in breast, ovarian and colon cancer tumors. The activation status of these driver pathways were then characterized using RNA sequencing data by constructing classification signature functions in training datasets and then testing the accuracy of the signatures in test datasets. The signature functions differentiate well tumors with nominated pathway activation from tumors with no signs of activation: average AUC equals to 0.83. Our results confirm that driver genomic alterations are distinctively displayed at the transcriptional level and that the transcriptional signatures can generally provide an alternative to DNA sequencing methods in detecting specific driver pathways. PMID:27098033

  19. Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Borrego-Soto, Gissela; Ortiz-Lopez, Rocio; Rojas-Martinez, Augusto, E-mail: arojasmtz@gmail.com, E-mail: augusto.rojasm@uanl.mx [Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León (Mexico)

    2015-10-15

    Breast cancer is the most common malignancy in women. Radiotherapy is frequently used in patients with breast cancer, but some patients may be more susceptible to ionizing radiation, and increased exposure to radiation sources may be associated to radiation adverse events. This susceptibility may be related to deficiencies in DNA repair mechanisms that are activated after cell-radiation, which causes DNA damage, particularly DNA double strand breaks. Some of these genetic susceptibilities in DNA-repair mechanisms are implicated in the etiology of hereditary breast/ovarian cancer (pathologic mutations in the BRCA 1 and 2 genes), but other less penetrant variants in genes involved in sporadic breast cancer have been described. These same genetic susceptibilities may be involved in negative radiotherapeutic outcomes. For these reasons, it is necessary to implement methods for detecting patients who are susceptible to radiotherapy-related adverse events. This review discusses mechanisms of DNA damage and repair, genes related to these functions, and the diagnosis methods designed and under research for detection of breast cancer patients with increased radiosensitivity. (author)

  20. Analysis of family function and influencing factors of childhood cancer%恶性肿瘤患儿家庭功能及影响因素分析

    Institute of Scientific and Technical Information of China (English)

    孙玉倩; 孙秉赋; 温颖娜; 刘瑞华; 王凤玲

    2013-01-01

    Objective To investigate the family function and its influencing factors of childhood cancer. Methods Cluster random sampling was conducted on 280 caregivers whose children with malignant tumor from 8 general hospitals in Beijing and Tangshan. Feetham family functioning survey was used for investigation. Results Both discrepant scroe and importance were high in items of " Problems with children" (3. 40 ± 1. 90) , and "Time miss housework" (3. 20 ± 1.94) ,the scroes of three dimensions were "The relationships between the family and social unit" (2. 18 ± 1. 05) , " The relationships between the family and each individal ( 1. 22 ± 0. 89) and " The relationships between the family and subsystems" (0. 98 ±0. 72). The high family's monthly income ( > 5 000 RMB) and long sickness duration ( >3 years) were predictors for impaired family functioning ( P 5 000元和患病时间>3年(P<0.05).结论 恶性肿瘤患儿的家庭功能低于正常家庭,家庭的社会功能(家庭与社会的关系)发挥较差,孩子的健康问题是家庭的主要问题.

  1. Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kan Casina WS

    2012-12-01

    Full Text Available Abstract Background There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC. MicroRNAs are stable in the circulation and may have utility as biomarkers of malignancy. We investigated whether levels of serum microRNA could discriminate women with high-grade SEOC from age matched healthy volunteers. Methods To identify microRNA of interest, microRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells. Total RNA was extracted from 500 μL aliquots of serum collected from patients with SEOC (n = 28 and age-matched healthy donors (n = 28. Serum microRNA levels were assessed by quantitative RT-PCR following preamplification. Results microRNA (miR-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers. miR-103, miR-92a and miR -638 had relatively invariant expression across all ovarian cell lines, and with small-nucleolar C/D box 48 (RNU48 were assessed in RNA extracted from serum as candidate endogenous normalizers. No correlation between serum levels and age were observed (age range 30-79 years for any of these microRNA or RNU48. Individually, miR-200a, miR-200b and miR-200c normalized to serum volume and miR-103 were significantly higher in serum of the SEOC cohort (P  Conclusions We identified serum microRNAs able to discriminate patients with high grade SEOC from age-matched healthy controls. The addition of these microRNAs to current testing regimes may improve diagnosis for women with SEOC.

  2. Symptom Profiles in Children With Advanced Cancer: Patient, Family Caregiver, and Oncologist Ratings

    Science.gov (United States)

    Zhukovsky, Donna S.; Rozmus, Cathy L.; Robert, Rhonda S.; Bruera, Eduardo; Wells, Robert J.; Chisholm, Gary B.; Allo, Julio A.; Cohen, Marlene Z.

    2016-01-01

    BACKGROUND Systematic symptom assessment is not routinely performed in pediatric oncology. The objectives of the current study were to characterize the symptoms of pediatric oncology outpatients and evaluate agreement between patient and proxy reports and the association between children’s ratings and oncologists’ treatment recommendations. METHODS Two versions of the pediatric Memorial Symptom Assessment Scale (pMSAS) were translated into Spanish. An age-appropriate and language-appropriate pMSAS was administered independently before visits to the oncologist to patients and family caregivers (caregivers) and after visits to consenting oncologists. Statistical analysis included Spearman correlation coefficients and weighted kappa values. RESULTS English and Spanish results were similar and were combined. A total of 60 children and their caregivers completed the pMSAS. The children had a median age of 10 years (range, 7–18 years); approximately 62% were male and 33% were Spanish-speaking. Fourteen oncologists completed the pMSAS for 25 patients. Nine patients (15%) had no symptoms and 38 patients (63%) reported ≥2 symptoms. The most common symptoms were fatigue (12 patients; 40%) and itch (9 patients; 30%) for the younger children and pain (15 patients; 50%) and lack of energy (13 patients; 45%) among the older children. Total and subscale score agreement varied by proxy type and subscale, ranging from fair to good for most comparisons. Agreement for individual symptoms between the patient and proxy ranged from a kappa of −0.30 (95% confidence interval, −0.43 to −0.01) to 0.91 (95% confidence interval, 0.75 to 1.00). Three of 51 symptomatic patients (6%) had treatment recommendations documented in the electronic health record. CONCLUSIONS Symptoms are common and cross several functional domains. Proxy and child reports are often not congruent, possibly explaining apparent undertreatment among this group of patients. PMID:26218240

  3. Experience of BRCA1/2 mutation-negative young women from families with hereditary breast and ovarian cancer: a qualitative study

    OpenAIRE

    Macrae, Lynn; de Souza, Alicia Navarro; Loiselle, Carmen G.; Wong, Nora

    2013-01-01

    Background Little is known about the experience of young women who become aware of their parent’s BRCA1 or BRCA2 (BRCA) mutation status as adolescents or young adults. There is also currently a gap in the literature pertaining to those who are found to be negative for their familial mutation. We aimed to investigate the experience of these mutation-negative young women from hereditary breast and ovarian cancer (HBOC) families. Methods Using a semi-structured questionnaire we interviewed 8 wom...

  4. MRI screening for breast cancer in women with familial or genetic predisposition : design of the Dutch National Study (MRISC)

    NARCIS (Netherlands)

    Kriege, M; Brekelmans, C T; Boetes, C; Rutgers, E J; Oosterwijk, J C; Tollenaar, R A; Manoliu, R A; Holland, R; de Koning, H J; Klijn, J G

    2001-01-01

    Mammography screening of women aged 50-70 years for breast cancer has proven to be effective in reducing breast cancer mortality. There is no consensus about the value of breast cancer screening in women aged 40-49 years. Five to ten per cent of all breast cancers are hereditary. One of the options

  5. Guidelines for Follow-Up of Women at High Risk for Inherited Breast Cancer: Consensus Statement from the Biomed 2 Demonstration Programme on Inherited Breast Cancer

    Directory of Open Access Journals (Sweden)

    P. Møller

    1999-01-01

    Full Text Available Protocols for activity aiming at early diagnosis and treatment of inherited breast or breast-ovarian cancer have been reported. Available reports on outcome of such programmes are considered here. It is concluded that the ongoing activities should continue with minor modifications. Direct evidence of a survival benefit from breast and ovarian screening is not yet available. On the basis of expert opinion and preliminary results from intervention programmes indicating good detection rates for early breast cancers and 5-year survival concordant with early diagnosis, we propose that women at high risk for inherited breast cancer be offered genetic counselling, education in ‘breast awareness’ and annual mammography and clinical expert examination from around 30 years of age. Mammography every second year may be sufficient from 60 years on. BRCA1 mutation carriers may benefit from more frequent examinations and cancer risk may be reduced by oophorectomy before 40–50 years of age. We strongly advocate that all activities should be organized as multicentre studies subjected to continuous evaluation to measure the effects of the interventions on long-term mortality, to match management options more precisely to individual risks and to prepare the ground for studies on chemoprevention.

  6. 晚期癌症病人家庭临终护理的研究进展%Research progress on family palliative care of advanced cancer patients

    Institute of Scientific and Technical Information of China (English)

    朱雅铃; 汪苗

    2015-01-01

    综述近年来国内外晚期癌症病人家庭护理模式的研究进展,探讨我国开展晚期癌症病人家庭临终护理存在的问题和解决方法,指出未来应着重培养专业的家庭临终医护人员,健全家庭临终护理的模式,从而为病人和家属提供全面、专业的照护与支持;逐步将家庭临终护理加入医保范围,加大对家庭临终护理的政策和财力支持,普及和推广家庭临终护理;加大宣传,帮助人们更新思想观念,关注人的基本权利。%It reviewed the research progress on home care of domestic and foreign advanced cancer patients in recent years.It probe into the existing problems and solutions of family palliative care of advanced cancer pa-tients,and pointed out the future should focus on the training of health care professional family palliative carer, improve the family palliative care model,and then to provide comprehensive and professional care and support for patients and their families;Family palliative care was gradually added into medicare,and the policy and fi-nancial support for family palliative care were increased,to popularize and promote the family palliative care;in-crease publicity and help people to update ideas and concern about the fundamental rights of human.

  7. 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

    Directory of Open Access Journals (Sweden)

    Desjardins Sylvie

    2009-06-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  8. Improving the management of people with a family history of breast cancer in primary care: before and after study of audit-based education.

    OpenAIRE

    Rafi, I.; Chowdhury, S.; Chan, T.; Jubber, I; Tahir, M.; de Lusignan, S.

    2013-01-01

    Background In England, guidance from National Institute for Clinical Excellence (NICE) states women with a family history of breast cancer presenting to primary care should be reassured or referred. We reviewed the evidence for interventions that might be applied in primary care and conducted an audit of whether low risk women are correctly advised and flagged. Methods We conducted a literature review to identify modifiable risk factors. We extracted routinely collected data from the computer...

  9. The GRAIDS Trial: a cluster randomised controlled trial of computer decision support for the management of familial cancer risk in primary care

    OpenAIRE

    Emery, J.; Morris, H.; R. Goodchild; Fanshawe, T.; Prevost, A.T.; Bobrow, M.; Kinmonth, A L

    2007-01-01

    The objective was to evaluate the effect of an assessment strategy using the computer decision support system (the GRAIDS software), on the management of familial cancer risk in British general practice in comparison with best current practice. The design included cluster randomised controlled trial, and involved forty-five general practice teams in East Anglia, UK. Randomised to GRAIDS (Genetic Risk Assessment on the Internet with Decision Support) support (intervention n=23) or comparison (...

  10. 家庭干预对乳腺癌患者家庭亲密度及适应性的影响%Influence of professional family intervention on family cohesion and adaptability of patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    胡阳; 王海燕; 杜彩梅; 阿斯亚·买买提; 王理瑛

    2014-01-01

    Objective To study the influence of the professional family intervention on cohesion and adaptability of breast cancer patients.Methods One hundred and twenty-eight breast cancer patients were randomly divided into control group and intervention group in equal number.The control group was given conventional nursing and the intervention group interventions including nursing instruction for their families and caregivers,mental instructions,and regular follow-ups in terms of life and rehabilitative instructions.A Family Adaptability and Cohesion Scale(FACESII-CV)was used for assessment before and after intervention.Result After intervention,the score on cohesion and adaptability of the intervention group were significantly higher than those of the intervention group before intervention and the control group(P<0.05).Conclusion The professional family interventions can effectively improve the family cohesion and adaptability of breast cancer patients.%目的:探讨家庭干预对乳腺癌患者家庭关系的影响。方法将128例术后乳腺癌患者随机分为对照组和干预组,每组各64例,对照组给予常规护理措施,干预组在此基础上针对患者家庭及主要照顾者实施干预,包括针对患者主要照顾者进行的护理指导;与患者及家属进行座谈,进行心理疏导;出院后定期电话回访,给予生活和康复指导等。干预前后用家庭亲密度和适应性量表中文版(family adaptability and cohesion scale,FACESII-CV)分别对干预组和对照组进行测评。结果干预后,干预组在家庭实际亲密度及家庭实际适应性得分均高于干预前和对照组;家庭亲密度和适应性不满意程度得分均低于干预前和对照组(均P<0.05)。结论家庭干预能有效地提高乳腺癌患者的家庭亲密度和适应性。

  11. Ovarian cancer patients' psychological distress: the role of physical impairment, perceived unsupportive family and friend behaviors, perceived control, and self-esteem.

    Science.gov (United States)

    Norton, Tina R; Manne, Sharon L; Rubin, Stephen; Hernandez, Enrique; Carlson, John; Bergman, Cynthia; Rosenblum, Norman

    2005-03-01

    Although research has indicated that illness-related and interpersonal stress are associated with greater psychological distress among cancer patients, little empirical attention has been given to mechanisms that account for these relationships. In the present study, 2 mechanisms for the association between illness-related stress (physical impairment) and interpersonal stress (family and friend unsupportive responses) and psychological distress of 143 ovarian cancer patients were examined cross-sectionally. Separate structural equation models tested whether physical impairment impacted patients' distress via decrements in perceived control over their illness and whether unsupportive behaviors impacted patients' distress via decrements in patients' self-esteem. Results supported the proposed models and suggest that perceived control and self-esteem are 2 mechanisms for explaining how illness-related and interpersonal stress may be associated with psychological distress among women with ovarian cancer.

  12. Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc: a multicentre randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Saadatmand Sepideh

    2012-10-01

    Full Text Available Abstract Background To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test. The aim of the Familial MRI Screening Study (FaMRIsc is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density. Methods/Design This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1 has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30–55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000, and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000. Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor. Discussion Personalized breast cancer screening

  13. Ethical, social and economic issues in familial breast cancer: a compilation of views from the E.C. Biomed II Demonstration Project.

    Science.gov (United States)

    Steel, M; Smyth, E; Vasen, H; Eccles, D; Evans, G; Møller, P; Hodgson, S; Stoppa-Lyonnet, D; Chang-Claude, J; Caligo, M; Morrison, P; Haites, N

    1999-10-01

    Demand for clinical services for familial breast cancer is continuing to rise across Europe. Service provision is far from uniform and, in most centres, its evolution has been determined by local conditions, specifically by local research interests, rather than by central planning. However, in a number of countries there is evidence of progress towards co-ordinated development and audit of clinics providing risk assessment, counselling, screening and, in some cases, prophylactic intervention. Much important information should emerge from continued observation and comparative assessment of these developments. In most countries for which relevant data are available, there is a distinct bias towards higher social class among those who avail themselves of clinic facilities (in line with findings from many other health-promotion initiatives). This should be addressed when considering future organisation of clinical services. Molecular genetic studies designed to identify the underlying mutations responsible for familial breast cancer are not generally regarded as part of the clinical service and are funded through research grants (if at all). Economic considerations suggest that there is a case for keeping this policy under review. Familial cancers throw into sharp relief certain ethical and legal issues that have received much recent attention from government advisory bodies, patients' representatives, professional commentators and the popular media. Two are of particular importance; first, the right to gain access to medical records of relatives, in order to provide accurate risk assessment for a given family member, versus the right to privacy in respect of personal medical information and, second, the obligation (or otherwise) to inform family members of their risk status if they have not actively sought that knowledge. The legal position seems to vary from country to country and, in many cases, is unclear. In view of pressures to establish uniform approaches to

  14. The International Testicular Cancer Linkage Consortium : A clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred

    NARCIS (Netherlands)

    Mai, Phuong L.; Friedlander, Michael; Tucker, Kathy; Phillips, Kelly-Anne; Hogg, David; Jewett, Michael A. S.; Lohynska, Radka; Daugaard, Gedske; Richard, Stephane; Bonaiti-Pellie, Catherine; Heidenreich, Axel; Albers, Peter; Bodrogi, Istvan; Geczi, Lajos; Olah, Edith; Daly, Peter A.; Guilford, Parry; Fossa, Sophie D.; Heimdal, Ketil; Liubchenko, Ludmila; Tjulandin, Sergei A.; Stoll, Hans; Weber, Walter; Easton, Douglas F.; Dudakia, Darshna; Huddart, Robert; Stratton, Michael R.; Einhorn, Lawrence; Korde, Larissa; Nathanson, Katherine L.; Bishop, Timothy; Rapley, Elizabeth A.; Greene, Mark H.

    2010-01-01

    Objectives: Familial aggregation of testicular germ cell tumor (TGCT) has been reported, but it is unclear if familial TGCT represents a unique entity with distinct clinicopathologic characteristics. Here we describe a collection of familial TGCT cases from an international consortium, in an effort

  15. Identification and Functional Testing of ERCC2 Mutations in a Multi-national Cohort of Patients with Familial Breast- and Ovarian Cancer.

    Science.gov (United States)

    Rump, Andreas; Benet-Pages, Anna; Schubert, Steffen; Kuhlmann, Jan Dominik; Janavičius, Ramūnas; Macháčková, Eva; Foretová, Lenka; Kleibl, Zdenek; Lhota, Filip; Zemankova, Petra; Betcheva-Krajcir, Elitza; Mackenroth, Luisa; Hackmann, Karl; Lehmann, Janin; Nissen, Anke; DiDonato, Nataliya; Opitz, Romy; Thiele, Holger; Kast, Karin; Wimberger, Pauline; Holinski-Feder, Elke; Emmert, Steffen; Schröck, Evelin; Klink, Barbara

    2016-08-01

    The increasing application of gene panels for familial cancer susceptibility disorders will probably lead to an increased proposal of susceptibility gene candidates. Using ERCC2 DNA repair gene as an example, we show that proof of a possible role in cancer susceptibility requires a detailed dissection and characterization of the underlying mutations for genes with diverse cellular functions (in this case mainly DNA repair and basic cellular transcription). In case of ERCC2, panel sequencing of 1345 index cases from 587 German, 405 Lithuanian and 353 Czech families with breast and ovarian cancer (BC/OC) predisposition revealed 25 mutations (3 frameshift, 2 splice-affecting, 20 missense), all absent or very rare in the ExAC database. While 16 mutations were unique, 9 mutations showed up repeatedly with population-specific appearance. Ten out of eleven mutations that were tested exemplarily in cell-based functional assays exert diminished excision repair efficiency and/or decreased transcriptional activation capability. In order to provide evidence for BC/OC predisposition, we performed familial segregation analyses and screened ethnically matching controls. However, unlike the recently published RECQL example, none of our recurrent ERCC2 mutations showed convincing co-segregation with BC/OC or significant overrepresentation in the BC/OC cohort. Interestingly, we detected that some deleterious founder mutations had an unexpectedly high frequency of > 1% in the corresponding populations, suggesting that either homozygous carriers are not clinically recognized or homozygosity for these mutations is embryonically lethal. In conclusion, we provide a useful resource on the mutational landscape of ERCC2 mutations in hereditary BC/OC patients and, as our key finding, we demonstrate the complexity of correct interpretation for the discovery of "bonafide" breast cancer susceptibility genes. PMID:27504877

  16. Identification and Functional Testing of ERCC2 Mutations in a Multi-national Cohort of Patients with Familial Breast- and Ovarian Cancer

    Science.gov (United States)

    Kuhlmann, Jan Dominik; Janavičius, Ramūnas; Foretová, Lenka; Lhota, Filip; Zemankova, Petra; Betcheva-Krajcir, Elitza; Mackenroth, Luisa; Lehmann, Janin; Nissen, Anke; DiDonato, Nataliya; Opitz, Romy; Thiele, Holger; Kast, Karin; Wimberger, Pauline; Holinski-Feder, Elke; Emmert, Steffen

    2016-01-01

    The increasing application of gene panels for familial cancer susceptibility disorders will probably lead to an increased proposal of susceptibility gene candidates. Using ERCC2 DNA repair gene as an example, we show that proof of a possible role in cancer susceptibility requires a detailed dissection and characterization of the underlying mutations for genes with diverse cellular functions (in this case mainly DNA repair and basic cellular transcription). In case of ERCC2, panel sequencing of 1345 index cases from 587 German, 405 Lithuanian and 353 Czech families with breast and ovarian cancer (BC/OC) predisposition revealed 25 mutations (3 frameshift, 2 splice-affecting, 20 missense), all absent or very rare in the ExAC database. While 16 mutations were unique, 9 mutations showed up repeatedly with population-specific appearance. Ten out of eleven mutations that were tested exemplarily in cell-based functional assays exert diminished excision repair efficiency and/or decreased transcriptional activation capability. In order to provide evidence for BC/OC predisposition, we performed familial segregation analyses and screened ethnically matching controls. However, unlike the recently published RECQL example, none of our recurrent ERCC2 mutations showed convincing co-segregation with BC/OC or significant overrepresentation in the BC/OC cohort. Interestingly, we detected that some deleterious founder mutations had an unexpectedly high frequency of > 1% in the corresponding populations, suggesting that either homozygous carriers are not clinically recognized or homozygosity for these mutations is embryonically lethal. In conclusion, we provide a useful resource on the mutational landscape of ERCC2 mutations in hereditary BC/OC patients and, as our key finding, we demonstrate the complexity of correct interpretation for the discovery of “bonafide” breast cancer susceptibility genes. PMID:27504877

  17. Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: Implications for genetic testing

    Institute of Scientific and Technical Information of China (English)

    Janos Papp; Marietta E Kovacs; Edith Olah

    2007-01-01

    AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families.METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplification (MLPA).RESULTS: Eighteen germline mutations (50%) were identified, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remAlning two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the definite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam Ⅰ/Ⅱ criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family.CONCLUSION: Our study describes for the first time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population.

  18. Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: Implications for genetic testing

    Science.gov (United States)

    Papp, Janos; Kovacs, Marietta E; Olah, Edith

    2007-01-01

    AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplification (MLPA). RESULTS: Eighteen germline mutations (50%) were identified, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the definite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam I/II criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family. CONCLUSION: Our study describes for the first time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population. PMID:17569143

  19. Prostate Cancer

    Science.gov (United States)

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  20. Src family kinase inhibitor PP2 efficiently inhibits cervical cancer cell proliferation through down-regulating phospho-Src-Y416 and phospho-EGFR-Y1173.

    Science.gov (United States)

    Kong, Lu; Deng, Zhihong; Shen, Haiying; Zhang, Yuxiang

    2011-02-01

    Tyrosine (Y) kinases inhibitors have been approved for targeted treatment of cancer. However, their clinical use is limited to some cancers and the mechanism of their action remains unclear. Previous study has indicated that PP2, a selective inhibitor of the Src family of non-receptor tyrosine kinases (nRTK), efficiently repressed cervical cancer growth in vitro and in vivo. In this regard, our aims are to explore the mechanism of PP2 on cervical cancer cell growth inhibition by investigating the suppressive divergence among PP1, PP2, and a negative control compound PP3. MTT results showed that three compounds had different inhibitory effects on proliferation of two cervical cancer cells, HeLa and SiHa, and PP2 was most efficient in a time- and dose-dependent manner. Moreover, we found 10 μM PP2 down-regulated pSrc-Y416 (P < 0.05), pEGFR-Y845 (P < 0.05), and -Y1173 (P < 0.05) expression levels, while 10 μM PP1 down-regulated pSrc-Y416 (P < 0.05) and pEGFR-Y845 (P < 0.05), but not pEGFR-Y1173; 10 μM PP3 down-regulated only pEGFR-Y1173 (P < 0.05). PP2 could modulate cell cycle arrest by up-regulating p21(Cip1) and p27(Kip1) in both HeLa and SiHa cells and down-regulating expression of cyclin A, and cyclin dependent kinase-2, -4 (Cdk-2, -4) in HeLa and of cyclin B and Cdk-2 in SiHa. Our results indicate that Src pathway and EGFR pathway play different roles in the proliferation of cervical cancer cells and PP2 efficiently reduces cervical cancer cell proliferation by reduction of both Src and EGFR activity.