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Sample records for breast-ovarian cancer families

  1. BRCA1 and BRCA2 Germline Mutations Screening in Algerian Breast/Ovarian Cancer Families

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    Farid Cherbal

    2010-01-01

    Full Text Available Background: Breast cancer is the leading cause of cancer death in women in Algeria. The contribution of BRCA1 and BRCA2 mutations to hereditary breast/ovarian cancer in Algerian population is largely unknown. Here, we describe analysis of BRCA1 and BRCA2 genes in 86 individuals from 70 families from an Algerian cohort with a personal and family history suggestive of genetic predisposition to breast cancer.

  2. BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk.

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    Fabrice Kwiatkowski

    Full Text Available Deleterious mutations in the BRCA genes are responsible for a small, but significant, proportion of breast and ovarian cancers (5 - 10 %. Proof of de novo mutations in hereditary breast/ovarian cancer (HBOC families is rare, in contrast to founder mutations, thousands of years old, that may be carried by as much as 1 % of a population. Thus, if mutations favoring cancer survive selection pressure through time, they must provide advantages that compensate for the loss of life expectancy.This hypothesis was tested within 2,150 HBOC families encompassing 96,325 individuals. Parameters included counts of breast/ovarian cancer, age at diagnosis, male breast cancer and other cancer locations. As expected, well-known clinical parameters discriminated between BRCA-mutated families and others: young age at breast cancer, ovarian cancer, pancreatic cancer and male breast cancer. The major fertility differences concerned men in BRCA-mutated families: they had lower first and mean age at paternity, and fewer remained childless. For women in BRCA families, the miscarriage rate was lower. In a logistic regression including clinical factors, the different miscarriage rate and men's mean age at paternity remained significant.Fertility advantages were confirmed in a subgroup of 746 BRCA mutation carriers and 483 non-carriers from BRCA mutated families. In particular, female carriers were less often nulliparous (9.1 % of carriers versus 16.0 %, p = 0.003 and had more children (1.8 ± 1.4 SD versus 1.5 ± 1.3, p = 0.002 as well as male carriers (1.7 ± 1.3 versus 1.4 ± 1.3, p = 0.024.Although BRCA mutations shorten the reproductive period due to cancer mortality, they compensate by improving fertility both in male and female carriers.

  3. Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer

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    Sruewing, J.P.; Brody, L.C.; Erdos, M.R. [National Institute of Health, Bethesda, MD (United States)] [and others

    1995-07-01

    Genetic epidemiological evidence suggests that mutations in BRCA1 may be responsible for approximately one half of early onset familial breast cancer and the majority of familial breast/ovarian cancer. The recent cloning of BRCA1 allows for the direct detection of mutations, but the feasibility of presymptomatic screening for cancer susceptibility is unknown. We analyzed genomic DNA from one affected individual from each of 24 families with at least three cases of ovarian or breast cancer, using SSCP assays. Variant SSCP bands were subcloned and sequenced. Allele-specific oligonucleotide hybridization was used to verify sequence changes and to screen DNA from control individuals. Six frameshift and two missense mutations were detected in 10 different families. A frameshift mutation was detected in a male proband affected with both breast and prostate cancer. A 40-bp deletion was detected in a patient who developed intra-abdominal carcinomatosis 1 year after prophylactic oophorectomy. Mutations were detected throughout the gene, and only one was detected in more than a single family. These results provide further evidence that inherited breast and ovarian cancer can occur as a consequence of a wide array of BRCA1 mutations. These results suggests that development of a screening test for BRCA1 mutations will be technically challenging. The finding of a mutation in a family with male breast cancer, not previously thought to be related to BRCA1, also illustrates the potential difficulties of genetic counseling for individuals known to carry mutations. 37 refs., 1 fig., 1 tab.

  4. 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

  5. BRCA1 and BRCA2 mutation analysis in breast-ovarian cancer families from northeastern Poland.

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    Perkowska, Magdalena; BroZek, Izabela; Wysocka, Barbara; Haraldsson, Karin; Sandberg, Therese; Johansson, Ulla; Sellberg, Gunilla; Borg, Ake; Limon, Janusz

    2003-05-01

    Sixty high-risk breast and/or ovarian cancer families from North-Eastern Poland were screened for germline mutations in BRCA1 (MIM# 113705) and BRCA2 (MIM# 600185), using a combination of protein truncation test, denaturing high-performance liquid chromatography and direct sequencing. Sixteen (27%) of the families were found to carry nine different BRCA mutations, including 14 families with BRCA1 mutation and two families with BRCA2 mutation. The results suggest the presence of two strong BRCA1 founder mutations in the Polish population - 5382insC (6 families) and 300T>G (Cys61Gly; 3 families). The remaining seven mutations were found in single families and included three previously reported BRCA1 mutations (185delAG, 2682C>T [Gln855Ter] and 3819del5), a novel BRCA1 mutation (IVS14+1G>A), as well as two BRCA2 mutations (4088delA and 7985G>A [Trp2586Ter]) not previously observed in Polish families. We confirm the strong influence of two Central-Eastern European BRCA1 founder mutations in familial breast and/or ovarian cancer in Poland. We also conclude that the Polish population has a more dispersed BRCA mutation spectrum than had been earlier thought. This warrants further careful BRCA mutation screening in order to optimise genetic counselling and disease prevention in affected families.

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

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    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...

  7. 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

  8. Genetic testing and first presymptomatic diagnosis in Moroccan families at high risk for breast/ovarian cancer.

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    Laarabi, Fatima Zahra; Jaouad, Imane Cherkaoui; Ouldim, Karim; Aboussair, Nisrine; Jalil, Abdelouahed; Gueddari, Brahim El Khalil El; Benjaafar, Noureddine; Sefiani, Abdelaziz

    2011-03-01

    Germline mutations in the BRCA1 and BRCA2 genes highly predispose to breast and ovarian cancers and are responsible for a substantial proportion of familial breast and ovarian cancers. No female individuals from families from Morocco affected by breast cancer with mutations of these genes have previously been reported, and clinicians in Morocco are unaccustomed to dealing with healthy female individuals carrying mutations in the BRCA genes. This study aimed to report the initial experience of a group of Moroccan investigators carrying out predictive genetic testing to detect a known familial mutation in healthy Moroccan females with a high risk of developing breast cancer and to introduce supervision of these asymptomatic female carriers as a new approach in the prevention and early diagnosis of breast and ovarian cancers in Morocco. Presymptomatic diagnosis was carried out using DNA genetic testing in 5 healthy Moroccan female individuals from three families with an elevated risk of developing breast cancer. These are the first Moroccan families reported to be affected by breast cancers associated with BRCA mutations. Presymptomatic diagnosis was carried out for breast cancer in 5 female individuals from three Moroccan families with BRCA mutations. Two of the families are the first reported incidence of the founder mutation Ashkenazi BRCA1-185_186delAG in Moroccan patients. The third family carried the known BRCA2 mutation c.5073dupA/p.trp1692metfsX3. We tested the presence of these mutations in 5 asymptomatic healthy females from the three families. Two sisters from family 1 carried the BRCA1-185_186delAG mutation, whereas the third female individual from family 2 carried the c.5073dupA/p.trp1692metfsX3 mutation. However, one healthy female individual and her mother from family 3 did not carry the familial mutation of the BRCA1 gene. This study found BRCA mutations in three asymptomatic subjects, suggesting that this is the first step towards the development of

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

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

    2010-01-01

    Mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2 are associated with increased risk of breast and ovarian cancer. Patients with mutations in both genes are rarely reported and often involve Ashkenazi founder mutations. Here we report the first identification of a Danish...... breast and ovarian cancer family heterozygote for mutations in the BRCA1 and BRCA2 genes. The BRCA1 nucleotide 5215G > A/c.5096G > A mutation results in the missense mutation Arg1699Gln, while the BRCA2 nucleotide 859 + 4A > G/c.631 + 4A > G is novel. Exon trapping experiments and reverse transcriptase...... (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...

  10. 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

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    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

  11. 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...

  12. 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...... cancer patients in whom a deleterious mutation in BRCA1 and BRCA2 was not detected by sequencing using the multiplex ligation-dependent probe amplification (MLPA) assay. We identified 15 patients with 7 different genomic rearrangements, including a BRCA1 exon 5-7 deletion with a novel breakpoint, a BRCA1...... exon 13 duplication, a BRCA1 exon 17-19 deletion, a BRCA1 exon 3-16 deletion, and a BRCA2 exon 20 deletion with a novel breakpoint as well as two novel BRCA1 exon 17-18 and BRCA1 exon 19 deletions. The large rearrangements in BRCA1 and BRCA2 accounted for 9.2% (15/163) of all BRCA1 and BRCA2 mutations...

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

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    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.

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

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    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.

  15. Familial aggregation of breast/ovarian cancer: age of onset along subsequent generations in Brazil Agregação familiar de câncer de mama e ovário: idade de manifestação em gerações subseqüentes no Brasil

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    Rosalina Jorge Koifman

    1998-01-01

    Full Text Available Antecedents of familial aggregation of breast and ovarian cancer are observed in only 5-8% of all breast cancer cases. Nevertheless, this variable displays one of the highest risk ratios associated to breast cancer outcome. Despite recent identification of genetic mutations associated with familial aggregation of these tumors, mainly at BRCA1 and BRCA2 genes, knowledge on the interaction between environmental agents in these families remains quite unclear. In this paper we ascertained the correlation among ages of the onset of breast/ovarian cancer in 260 Brazilian families with those cancer aggregation. Further we estimated the median age of the onset of breast cancer among four generations. We observed that the higher the number of family cancer cases, the highest is the correlation of ages for the onset of breast cancer. We also observed a 8-10 year decline in the mean age-of-onset of breast/ovarian cancer from one generation to another in the studied families. If these results could be confirmed elsewhere, we believe that the hypothesis of interaction between environmental risks factors in families indeed showing breast/ovarian cancer aggregation is reinforced.A presença de antecedentes de agregação familiar de câncer de mama e ovário é observada em apenas 5% a 8% de todos os casos de câncer de mama. Esta variável, entretanto, é uma das que apresenta maior razão de riscos para o desfecho câncer de mama. Apesar da identificação recente de mutações genéticas associadas com a agregação familiar destes tumores, sobretudo nos genes BRCA1 e BRCA2, o conhecimento sobre as interações entre fatores ambientais e genéticos nessas famílias permanece relativamente obscuro. Neste trabalho, determinamos a correlação das idades de início de câncer de mama e ovário em 260 famílias com agrupação daqueles tumores. Posteriormente, foi estimada a idade média de início destes tumores ao longo de quatro gerações. Observou-se que

  16. Association of insulin resistance with breast, ovarian, endometrial and cervical cancers in non-diabetic women.

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    Sun, Wanwan; Lu, Jieli; Wu, Shengli; Bi, Yufang; Mu, Yiming; Zhao, Jiajun; Liu, Chao; Chen, Lulu; Shi, Lixin; Li, Qiang; Yang, Tao; Yan, Li; Wan, Qin; Liu, Yan; Wang, Guixia; Luo, Zuojie; Tang, Xulei; Chen, Gang; Huo, Yanan; Gao, Zhengnan; Su, Qing; Ye, Zhen; Wang, Youmin; Qin, Guijun; Deng, Huacong; Yu, Xuefeng; Shen, Feixia; Chen, Li; Zhao, Liebin; Wang, Tiange; Sun, Jichao; Xu, Min; Xu, Yu; Chen, Yuhong; Dai, Meng; Zhang, Jie; Zhang, Di; Lai, Shenghan; Li, Donghui; Ning, Guang; Wang, Weiqing

    2016-01-01

    Hyperinsulinemia and insulin resistance were reported to play a crucial role in diabetes-cancer relationship. This study aimed to explore the associations between insulin resistance and several female cancers in a non-diabetic population. This cross-sectional study was conducted in 121,230 middle-aged and elderly non-diabetic women. Cancer diagnosis was self-reported and further validated by medical records. Insulin resistance was defined as homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.50. The prevalence of both premenopausal and postmenopausal breast cancer, postmenopausal ovarian cancer and premenopausal endometrial cancer were higher in insulin-resistant participants than in insulin-sensitive participants (premenopausal breast cancer, 0.45 vs 0.28%; postmenopausal breast cancer, 0.86 vs 0.63%; postmenopausal ovarian cancer, 0.17 vs 0.09%; premenopausal endometrial cancer, 0.43 vs 0.25%, respectively, all P insulin resistance had higher odds ratio (OR) of breast cancer, both premenopausal and postmenopausal (OR 1.98, 95% confidence interval (CI) 1.19-3.32; OR 1.29, 95% CI 1.01-1.63), postmenopausal ovarian cancer (OR 2.17, 95% CI 1.10-3.40) as well as total endometrial cancer (OR 1.47, 95% CI 1.02-2.12). Subgroup analysis revealed that the possitive association between insulin resistance and risk of prevalent breast cancer was observed in popualtion with younger age, overweight or obesity, higher education and impaired glucose tolerance (IGR). No relationships were observed for the risk of prevalent cervical cancers with insulin resistance. Non-diabetic women with insulin resistance had higher risk of prevalent breast, ovarian and endomatrial cancer, which suggests special attentions to these female cancer screening and prevention.

  17. 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...

  18. Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

    Science.gov (United States)

    Kar, Siddhartha P.; Beesley, Jonathan; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J.; Thompson, Deborah J.; Kibel, Adam S.; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K.; Gentry-Maharaj, Aleksandra; Whittemore, Alice S.; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H.; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B.; Burwinkel, Barbara; Karlan, Beth Y.; Nordestgaard, Børge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Høgdall, Claus K.; Teerlink, Craig C.; Kang, Daehee; Tessier, Daniel C.; Schaid, Daniel J.; Stram, Daniel O.; Cramer, Daniel W.; Neal, David E.; Eccles, Diana; Flesch-Janys, Dieter; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A.; Darabi, Hatef; Salvesen, Helga B.; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L.; Benítez, Javier; Doherty, Jennifer A.; Permuth, Jennifer B.; Chang-Claude, Jenny; Donovan, Jenny L.; Dennis, Joe; Schildkraut, Joellen M.; Schleutker, Johanna; Hopper, John L.; Kupryjanczyk, Jolanta; Park, Jong Y.; Figueroa, Jonine; Clements, Judith A.; Knight, Julia A.; Peto, Julian; Cunningham, Julie M.; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H.; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B.; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Fitzgerald, Liesel M.; Cook, Linda S.; Cannon-Albright, Lisa; Hooning, Maartje J.; Pike, Malcolm C.; Bolla, Manjeet K.; Luedeke, Manuel; Teixeira, Manuel R.; Goodman, Marc T.; Schmidt, Marjanka K.; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W.; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C.; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A. T.; Hou, Ming-Feng; Schoemaker, Minouk J.; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; Le, Nhu D.; Orr, Nick; Wentzensen, Nicolas; Pashayan, Nora; Peterlongo, Paolo; Guénel, Pascal; Brennan, Paul; Paulo, Paula; Webb, Penelope M.; Broberg, Per; Fasching, Peter A.; Devilee, Peter; Wang, Qin; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K.; Stephenson, Robert A.; MacInnis, Robert J.; Hoover, Robert N.; Winqvist, Robert; Ness, Roberta; Milne, Roger L.; Travis, Ruth C.; Benlloch, Sara; Olson, Sara H.; McDonnell, Shannon K.; Tworoger, Shelley S.; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N.; Bojesen, Stig E.; Gapstur, Susan M.; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L.J.; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J.; Edwards, Todd L.; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J.; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L.; Berchuck, Andrew; Dunning, Alison M.; Simard, Jacques; Haiman, Christopher A.; Spurdle, Amanda; Sellers, Thomas A.; Hunter, David J.; Henderson, Brian E.; Kraft, Peter; Chanock, Stephen J.; Couch, Fergus J.; Hall, Per; Gayther, Simon A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D.P.; Lambrechts, Diether

    2016-01-01

    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 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. PMID:27432226

  19. 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.

  20. 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...

  1. The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers.

    Science.gov (United States)

    Ganmaa, Davaasambuu; Sato, Akio

    2005-01-01

    The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that "man has been drinking cows' milk for around 2000 years without apparent harm." However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0

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

    NARCIS (Netherlands)

    K. Lawrenson (Kate); S. Kar (Siddhartha); K. McCue (Karen); Kuchenbaeker, K. (Karoline); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); J. Beesley (Jonathan); S.J. Ramus (Susan); Li, Q. (Qiyuan); Delgado, M.K. (Melissa K.); J.M. Lee (Janet M.); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Arndt, V. (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); E.V. Bandera (Elisa); M. Barile (Monica); Barkardottir, R.B. (Rosa B.); D. Barrowdale (Daniel); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berchuck (Andrew); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); W.J. Blot (William); N.V. Bogdanova (Natalia); Bojesen, A. (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet K.); B. Bonnani (Bernardo); A.-L. Borresen-Dale (Anne-Lise); H. Brauch (Hiltrud); P. Brennan (Paul); H. Brenner (Hermann); F. Bruinsma (Fiona); J. Brunet (Joan); S.A.B.S. Buhari (Shaik Ahmad Bin Syed); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra); Q. Cai (Qiuyin); T. Caldes (Trinidad); I. Campbell (Ian); Canniotto, R. (Rikki); J. Chang-Claude (Jenny); Chiquette, J. (Jocelyne); Choi, J.-Y. (Ji-Yeob); K.B.M. Claes (Kathleen B.M.); L.S. Cook (Linda S.); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); C. Cybulski (Cezary); K. Czene (Kamila); M.B. Daly (Mary B.); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); J. Dennis (Joe); P. Devilee (Peter); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); M. Dumont (Martine); H. Ehrencrona (Hans); B. Ejlertsen (Bent); S.D. Ellis (Steve); C. Engel (Christoph); E. Lee (Eunjung); Evans, D.G. (D. Gareth); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); H. Flyger (Henrik); L. Foretova (Lenka); F. Fostira (Florentia); W.D. Foulkes (William); B.L. Fridley (Brooke); E. Friedman (Eitan); D. Frost (Debra); Gambino, G. (Gaetana); P.A. Ganz (Patricia A.); J. Garber (Judy); M. García-Closas (Montserrat); A. Gentry-Maharaj (Aleksandra); M. Ghoussaini (Maya); G.G. Giles (Graham); R. Glasspool (Rosalind); A.K. Godwin (Andrew K.); M.S. Goldberg (Mark); D. Goldgar (David); A. González-Neira (Anna); E.L. Goode (Ellen); M.T. Goodman (Marc); M.H. Greene (Mark H.); J. Gronwald (Jacek); P. Guénel (Pascal); C.A. Haiman (Christopher A.); P. Hall (Per); Hallberg, E. (Emily); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. harrington (Patricia); J.M. Hartman (Joost); N. Hassan (Norhashimah); S. Healey (Sue); P.U. Heitz; J. Herzog (Josef); E. Høgdall (Estrid); C.K. Høgdall (Claus); F.B.L. Hogervorst (Frans); A. Hollestelle (Antoinette); J.L. Hopper (John); P.J. Hulick (Peter); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); H. Ito (Hidemi); A. Jakubowska (Anna); R. Janavicius (Ramunas); A. Jensen (Allan); E.M. John (Esther); Johnson, N. (Nichola); M. Kabisch (Maria); D. Kang (Daehee); M.K. Kapuscinski (Miroslav K.); Karlan, B.Y. (Beth Y.); S. Khan (Sofia); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); J. Kupryjanczyk (Jolanta); A. Kwong (Ava); M. de La Hoya (Miguel); Y. Laitman (Yael); Lambrechts, D. (Diether); N.D. Le (Nhu D.); K. De Leeneer (Kim); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); A. Lindblom (Annika); J. Long (Jirong); A. Lophatananon (Artitaya); J.T. Loud (Jennifer); K.H. Lu (Karen); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); L. Le Marchand (Loic); S. Margolin (Sara); F. Marme (Frederick); L.F. Massuger (Leon); K. Matsuo (Keitaro); S. Mazoyer (Sylvie); L. McGuffog (Lesley); C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); U. Menon (Usha); Mensenkamp, A.R. (Arjen R.); R.L. Milne (Roger); M. Montagna (Marco); K.B. Moysich (Kirsten); K.R. Muir (K.); A.-M. Mulligan (Anna-Marie); K.L. Nathanson (Katherine); R.B. Ness (Roberta); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); R.L. Nussbaum (Robert L.); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); C. Olswold (Curtis); D.M. O'Malley (David M.); I. Orlow (Irene); N. Orr (Nick); A. Osorio (Ana); Park, S.K. (Sue Kyung); C.L. Pearce (Celeste); T. Pejovic (Tanja); P. Peterlongo (Paolo); G. Pfeiler (Georg); C. Phelan (Catherine); E.M. Poole (Elizabeth); K. Pykäs (Katri); P. Radice (Paolo); J. Rantala (Johanna); M.U. Rashid (Muhammad); G. Rennert (Gad); V. Rhenius (Valerie); K. Rhiem (Kerstin); H. Risch (Harvey); G.C. Rodriguez (Gustavo); M.A. Rossing (Mary Anne); Rudolph, A. (Anja); H.B. Salvesen (Helga); Sangrajrang, S. (Suleeporn); Sawyer, E.J. (Elinor J.); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); T.A. Sellers (Thomas A.); C.M. Seynaeve (Caroline); Shah, M. (Mitul); C.-Y. Shen (Chen-Yang); X.-O. Shu (Xiao-Ou); W. Sieh (Weiva); C.F. Singer (Christian); O. Sinilnikova (Olga); S. Slager (Susan); H. Song (Honglin); Soucy, P. (Penny); M.C. Southey (Melissa); M. Stenmark-Askmalm (Marie); D. Stoppa-Lyonnet (Dominique); C. Sutter (Christian); A.J. Swerdlow (Anthony ); Tchatchou, S. (Sandrine); P.J. Teixeira; S.-H. Teo; K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); M.G. Tibiletti (Maria Grazia); L. Tihomirova (Laima); S. Tognazzo (Silvia); A.E. Toland (Amanda); I.P. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); C.-C. Tseng (Chiu-Chen); N. Tung (Nadine); Tworoger, S.S. (Shelley S.); C. Vachon (Celine); Van Den Ouweland, A.M.W. (Ans M.W.); Van Doorn, H.C. (Helena C.); E.J. van Rensburg (Elizabeth); L.J. van 't Veer (Laura); A. Vanderstichele (Adriaan); I. Vergote (Ignace); J. Vijai (Joseph); Wang, Q. (Qin); S. Wang-Gohrke (Shan); J.N. Weitzel (Jeffrey); N. Wentzensen (N.); A.S. Whittemore (Alice); H. Wildiers (Hans); R. Winqvist (Robert); A.H. Wu (Anna); Yannoukakos, D. (Drakoulis); S.-Y. Yoon (Sook-Yee); J-C. Yu (Jyh-Cherng); W. Zheng (Wei); Y. Zheng (Ying); Khanna, K.K. (Kum Kum); J. Simard (Jacques); A.N.A. Monteiro (Alvaro N.); J.D. French (Juliet); F.J. Couch (Fergus); M. Freedman (Matthew); D.F. Easton (Douglas F.); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); S.L. Edwards (Stacey); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); S.A. Gayther (Simon); D. Bowtell (David); A. DeFazio (Anna); P. Webb (Penny); M.-A. Collonge-Rame; Damette, A. (Alexandre); E. Barouk-Simonet (Emmanuelle); F. Bonnet (Françoise); V. Bubien (Virginie); N. Sevenet (Nicolas); M. Longy (Michel); P. Berthet (Pascaline); D. Vaur (Dominique); L. Castera (Laurent); S.F. Ferrer; Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); F. Coron (Fanny); L. Faivre (Laurence); Baurand, A. (Amandine); Jacquot, C. (Caroline); Bertolone, G. (Geoffrey); Lizard, S. (Sarab); D. Leroux (Dominique); H. Dreyfus (Hélène); C. Rebischung (Christine); Peysselon, M. (Magalie); J.-P. Peyrat; J. Fournier (Joëlle); F. Révillion (Françoise); C. Adenis (Claude); L. Vénat-Bouvet (Laurence); M. Léone (Mélanie); N. Boutry-Kryza (N.); A. Calender (Alain); S. Giraud (Sophie); C. Verny-Pierre (Carole); C. Lasset (Christine); V. Bonadona (Valérie); Barjhoux, L. (Laure); H. Sobol (Hagay); V. Bourdon (Violaine); Noguchi, T. (Tetsuro); A. Remenieras (Audrey); I. Coupier (Isabelle); P. Pujol (Pascal); J. Sokolowska (Johanna); M. Bronner (Myriam); C.D. Delnatte (Capucine); Bézieau, S. (Stéphane); Mari, V. (Véronique); M. Gauthier-Villars (Marion); B. Buecher (Bruno); E. Rouleau (Etienne); L. Golmard (Lisa); V. Moncoutier (Virginie); M. Belotti (Muriel); A. de Pauw (Antoine); Elan, C. (Camille); Fourme, E. (Emmanuelle); Birot, A.-M. (Anne-Marie); Saule, C. (Claire); Laurent, M. (Maïté); C. Houdayer (Claude); F. Lesueur (Fabienne); N. Mebirouk (Noura); F. Coulet (Florence); C. Colas (Chrystelle); F. Soubrier; Warcoin, M. (Mathilde); F. Prieur (Fabienne); M. Lebrun (Marine); C. Kientz (Caroline); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); C. Toulas (Christine); R. Guimbaud (Rosine); L. Gladieff (Laurence); V. Feillel (Viviane); I. Mortemousque (Isabelle); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); M. Guillaud-Bataille (Marine); H. Gregory (Helen); Z. Miedzybrodzka (Zosia); P.J. Morrison (Patrick); A. Donaldson (Alan); M.T. Rogers (Mark); M.J. Kennedy (John); M.E. Porteous (Mary); A. Brady (A.); J. Barwell (Julian); Foo, C. (Claire); F. Lalloo (Fiona); L. Side (Lucy); J. Eason (Jacqueline); Henderson, A. (Alex); L.J. Walker (Lisa); J. Cook (Jackie); Snape, K. (Katie); A. Murray (Alexandra); E. McCann (Emma); M.A. Rookus (Matti); F.E. van Leeuwen (F.); L. van der Kolk (Lizet); M.K. Schmidt (Marjanka); N.S. Russell (Nicola); J.L. de Lange (J.); Wijnands, R.; J.M. Collée; M.J. Hooning (Maartje); Seynaeve, C.; C.H.M. van Deurzen (Carolien); A.I.M. Obdeijn (Inge-Marie); C.J. van Asperen (Christi); R.A.E.M. Tollenaar (Rob); T.C.T.E.F. van Cronenburg; C.M. Kets; M.G.E.M. Ausems (Margreet); C. van der Pol (Carmen); T.A.M. van Os (Theo); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); E.B. Gómez García (Encarna); J.C. Oosterwijk (Jan); M.J. Mourits; G.H. de Bock (Geertruida); H. Vasen (Hans); Siesling, S.; Verloop, J.; L.I.H. Overbeek (Lucy); S.B. Fox (Stephen); J. Kirk (Judy); G.J. Lindeman; M. Price (Melanie)

    2016-01-01

    textabstractA 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

  3. 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...

  4. 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.

  5. 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

    BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P...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-negative...

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

    Science.gov (United States)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J; Li, Qiyuan; Delgado, Melissa K; Lee, Janet M; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Bandera, Elisa V; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Matthias W; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B M; Cook, Linda S; Cox, Angela; Cramer, Daniel W; Cross, Simon S; Cybulski, Cezary; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A; Domchek, Susan M; Dorfling, Cecilia M; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Engel, Christoph; Lee, Eunjung; Evans, D Gareth; Fasching, Peter A; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fridley, Brooke L; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G; Glasspool, Rosalind; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Goode, Ellen L; Goodman, Marc T; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V O; Harrington, Patricia A; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K; Hogervorst, Frans B L; Hollestelle, Antoinette; Hopper, John L; Hulick, Peter J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y; Khan, Sofia; Kiemeney, Lambertus A; Kjaer, Susanne Kruger; Knight, Julia A; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F A G; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R; Milne, Roger L; Montagna, Marco; Moysich, Kirsten B; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Ness, Roberta B; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Poole, Elizabeth M; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schildkraut, Joellen M; Schmidt, Marjanka K; Schmutzler, Rita K; Sellers, Thomas A; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F; Sinilnikova, Olga M; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R; Teo, Soo H; Terry, Kathryn L; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tung, Nadine; Tworoger, Shelley S; Vachon, Celine; van den Ouweland, Ans M W; van Doorn, Helena C; van Rensburg, Elizabeth J; Van't Veer, Laura J; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N; Wentzensen, Nicolas; Whittemore, Alice S; Wildiers, Hans; Winqvist, Robert; Wu, Anna H; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N; French, Juliet D; Couch, Fergus J; Freedman, Matthew L; Easton, Douglas F; Dunning, Alison M; Pharoah, Paul D; Edwards, Stacey L; Chenevix-Trench, Georgia; Antoniou, Antonis C; Gayther, Simon A

    2016-09-07

    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-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P<2 × 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.

  7. Familial pancreatic cancer: Concept, management and issues

    Science.gov (United States)

    Matsubayashi, Hiroyuki; Takaori, Kyoichi; Morizane, Chigusa; Maguchi, Hiroyuki; Mizuma, Masamichi; Takahashi, Hideaki; Wada, Keita; Hosoi, Hiroko; Yachida, Shinichi; Suzuki, Masami; Usui, Risa; Furukawa, Toru; Furuse, Junji; Sato, Takamitsu; Ueno, Makoto; Kiyozumi, Yoshimi; Hijioka, Susumu; Mizuno, Nobumasa; Terashima, Takeshi; Mizumoto, Masaki; Kodama, Yuzo; Torishima, Masako; Kawaguchi, Takahisa; Ashida, Reiko; Kitano, Masayuki; Hanada, Keiji; Furukawa, Masayuki; Kawabe, Ken; Majima, Yoshiyuki; Shimosegawa, Toru

    2017-01-01

    Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion ( Caucasian) and a younger onset are common also in FPC. In European countries, “anticipation” is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (PanIN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990s and several surveillance projects for high-risk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.

  8. A novel de novo BRCA2 mutation of paternal origin identified in a Spanish woman with early onset bilateral breast cancer.

    Science.gov (United States)

    Diez, Orland; Gutiérrez-Enríquez, Sara; Mediano, Carmen; Masas, Miriam; Saura, Cristina; Gadea, Neus; Balmaña, Judith

    2010-05-01

    Germ line 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 in any of these genes is primarily based on a positive family history of breast/ovarian cancer or early onset of the disease. In the course of mutation screening of the BRCA1 and BRCA2 genes in a hospital based series of patients with risk factors for hereditary breast/ovarian cancer, we identified a novel germ line mutation in the BRCA2 gene (c.51dupA) in a patient with early onset bilateral breast cancer and no family history of the disease. None of her parents carried the mutation, and paternity was confirmed. Subsequent molecular analysis demonstrated that the mutation was a novel de novo germ line mutation located in the paternal allele of the BRCA2 gene.

  9. MTHFR C677T polymorphism and breast, ovarian cancer risk: a meta-analysis of 19,260 patients and 26,364 controls

    Science.gov (United States)

    He, Lilin; Shen, Yongxiang

    2017-01-01

    Objective Previous studies have found that many gene variations can be detected in both breast cancer and ovarian cancer, which is beneficial for the elaboration of the molecular origin of breast and ovarian cancer. Furthermore, many studies have explored the association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with the risk of breast cancer and/or ovarian cancer; however, the results remained inconclusive. Therefore, this study conducted a systematic review and meta-analysis to evaluate the association between MTHFR C677T polymorphism and the risk of breast and ovarian cancer. Materials and methods A total of 50 studies with 19,260 cases and 26,364 controls including 39 studies for breast cancer and 8 studies for ovarian cancer were identified on searching through PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP). Allele model, dominant model, recessive model, homozygous model, and co-dominant model were applied to evaluate the association of MTHFR C677T polymorphism with breast cancer and/or ovarian cancer risk. Moreover, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association between MTHFR C677T polymorphism and breast and ovarian cancer risk. Results A significantly increased breast cancer risk was observed in the overall analysis (for C vs T, OR =1.19, CI: 1.12–1.28, P<0.05; for CC vs TT, OR =1.20, CI: 1.10–1.23, P<0.05; for (CT+CC) vs TT, OR =1.19, CI: 1.11–1.27, P<0.05; for CC vs (CT+TT), OR =1.19, CI: 1.79–1.95, P<0.05), while no significantly increased ovarian cancer risk was detected. In the subgroup analysis based on ethnicity, a significant association of breast cancer and/or ovarian cancer risk with MTHFR C677T polymorphism was observed in Asians. Interestingly, there was no significant association between MTHFR C677T polymorphism and ovarian cancer risk in

  10. 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 autoanti...

  11. 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

    Background: In some solid cancers a survival benefit has been observed for patients who had chemotherapy-induced neutropenia. The prognostic impact of baseline and nadir blood neutrophils was assessed in the present study. Methods: Data on patients with breast cancer st.I-IV, ovarian cancer st.......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...... elevated neutrophil count was associated with short survival (p

  12. 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.

  13. Genetic testing for hereditary breast and ovarian cancer: responsibility and choice.

    Science.gov (United States)

    d'Agincourt-Canning, Lori

    2006-01-01

    Genetic testing for hereditary breast-ovarian cancer has become an important part of clinical genetics practice. Although considerable work has focused on the psychological impact of this technology, there has been little research into the moral implications of genetic information on hereditary cancer families. In this article, the author examines moral issues related to individuals' decisions to seek or decline testing. In-depth interviews with 53 participants make up the core of the research. Analysis of participants' accounts illustrates how the decision to be tested (or not) interconnects with moral agency and aspects of self (embodied, familial-relational, and civic self). The findings form the foundation for inquiry into conceptualization of moral responsibility, autonomy, and choice. They also provide insight that might assist clinicians to understand more fully the needs and responses of those who seek genetic testing for hereditary breast-ovarian cancer.

  14. 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.

  15. BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland.

    Science.gov (United States)

    Ratajska, Magdalena; Brozek, Izabela; Senkus-Konefka, Elzbieta; Jassem, Jacek; Stepnowska, Magdalena; Palomba, Grazia; Pisano, Marina; Casula, Milena; Palmieri, Giuseppe; Borg, Ake; Limon, Janusz

    2008-01-01

    Sixty-four Polish families with a history of breast and/or ovarian cancer were screened for mutations in the BRCA1/2 genes using a combination of denaturing high performance liquid chromatography (DHPLC) and sequencing. Two thirds (43/64; 67%) of the families were found to carry deleterious mutations, of which the most frequent were BRCA1 5382insC (n=22/43; 51%) and Cys61Gly (n=9/43; 20%). Two other recurrent mutations were BRCA1 185delAG (n=3) and 3819del5 (n=4), together accounting for 16% of the 43 mutation-positive cases. We also found three novel mutations (BRCA1 2991del5, BRCA2 6238ins2del21 and 8876delC) which combined with findings from our earlier study of 60 Northern Polish families. Moreover, screening of 43 BRCA1/2 negative families for the presence of large rearrangements by multiplex ligation-dependent probe amplification (MLPA) resulted in the finding of two additional BRCA1 mutations: a deletion of exons 1A, 1B and 2, and a deletion of exons 17-19, both present in single families. We conclude that the Polish population has a diverse mutation spectrum influenced by strong founder effects. However, families with strong breast/ovarian cancer history who are negative for these common mutations should be offered a complete BRCA gene screening, including MLPA analysis.

  16. 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

  17. Initial clinical validation of Health Heritage, a patient-facing tool for personal and family history collection and cancer risk assessment.

    Science.gov (United States)

    Baumgart, Leigh A; Postula, Kristen J Vogel; Knaus, William A

    2016-04-01

    Personal and family health histories remain important independent risk factors for cancer; however they are currently not being well collected or used effectively. Health Heritage was designed to address this need. The purpose of this study was to validate the ability of Health Heritage to identify patients appropriate for further genetic evaluation and to accurately stratify cancer risk. A retrospective chart review was conducted on 100 random patients seen at an adult genetics clinic presenting with concern for an inherited predisposition to cancer. Relevant personal and family history obtained from the patients' medical records was entered into Health Heritage. Recommendations by Health Heritage were compared to national guidelines of eligibility for genetic evaluation. Agreement between Health Heritage referral for genetic evaluation and guideline eligibility for genetic evaluation was 97% (sensitivity 98% and specificity 88%). Risk stratification for cancer was also compared between Health Heritage and those documented by a geneticist. For patients at increased risk for breast, ovarian, or colorectal cancer as determined by the geneticist, risk stratification by Health Heritage agreed 90, 93, and 75%, respectively. Discordances in risk stratification were attributed to both complex situations better handled by the geneticist and Health Heritage's adherence to incorporating all information into its algorithms. Health Heritage is a clinically valid tool to identify patients appropriate for further genetic evaluation and to encourage them to confirm the assessment and management recommendations with cancer genetic experts. Health Heritage also provides an estimate of cancer risk that is complementary to a genetics team.

  18. BRCA1, BRCA2 and CHEK2 (1100 del C) germline mutations in hereditary breast and ovarian cancer families in South India.

    Science.gov (United States)

    Rajkumar, Thangarajan; Soumittra, Nagasamy; Nancy, Nirmala Karunakaran; Swaminathan, Rajaraman; Sridevi, Veluswami; Shanta, Vishwanathan

    2003-01-01

    Cancer of the breast is the second most common cancer seen among Indian women. This study describes the use of DHPLC for mutation analysis for BRCA1, BRCA2 and CHEK2 (1100delC) in 22 patients with a family history of breast and/or ovarian cancer and early onset breast cancer (codon, potentially leading to a truncated protein. Two of these were in BRCA1 (one was a novel 5 base deletion) and one in the BRCA2 gene. No patient was found in our series to have the CHEK2 (1100delC) mutation. DNA from a healthy blood donor and all but one of the 22 patients, demonstrated polymorphisms in BRCA1 and/or BRCA2 genes. This is the first study from South India, on BRCA1, BRCA2 & CHEK2 (1100 del C) mutations in patients with a family history of breast and/or ovarian cancer and early onset breast/ovarian cancer, using the sensitive DHPLC approach.

  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. 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.

  1. 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.

  2. Psychological impact of genetic testing for cancer susceptibility: an update of the literature.

    Science.gov (United States)

    Meiser, Bettina

    2005-12-01

    This article presents an overview of the rapidly evolving body of literature on the psychological impact of genetic testing for hereditary breast/ovarian cancer susceptibility, hereditary non-polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). Uptake of genetic testing for BRCA1/2 and HNPCC-related mutations is more consistently related to psychological factors, rather than sociodemographic variables. Most studies on the psychological impact of genetic testing amongst individuals who have never been affected by cancer demonstrate that non-carriers derive significant psychological benefits from genetic testing, while no adverse effects have been observed amongst carriers. These benefits are more clear-cut for HNPCC, compared to hereditary breast/ovarian cancer, reflecting differences in risk management options. The few studies available on individuals affected with cancer indicate that the impact of genetic testing is mediated and amplified by their former experience of cancer. Future directions and challenges of research in this area are reviewed. In particular, more empirical data are needed on the broader impact of genetic testing on those with inconclusive results or results of uncertain significance. As genetic testing is becoming available for other types of familial cancer, additional investigations will be needed as there is evidence to suggest that the impact of genetic testing may be unique to each type of familial cancer.

  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, histopathologic...

  4. 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.

  5. 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.

  6. Large family with both parents affected by distinct BRCA1 mutations: implications for genetic testing

    Directory of Open Access Journals (Sweden)

    Sokolenko Anna P

    2009-01-01

    Full Text Available Abstract Although the probability of both parents being affected by BRCA1 mutations is not negligible, such families have not been systematically described in the literature. Here we present a large breast-ovarian cancer family, where 3 sisters and 1 half-sister inherited maternal BRCA1 5382insC mutation while the remaining 2 sisters carried paternal BRCA1 1629delC allele. No BRCA1 homozygous mutations has been detected, that is consistent with the data on lethality of BRCA1 knockout mice. This report exemplifies that the identification of a single cancer-predisposing mutation within the index patient may not be sufficient in some circumstances. Ideally, all family members affected by breast or ovarian tumor disease have to be subjected to the DNA testing, and failure to detect the mutation in any of them calls for the search of the second cancer-associated allele.

  7. Large family with both parents affected by distinct BRCA1 mutations: implications for genetic testing

    Science.gov (United States)

    Sokolenko, Anna P; Voskresenskiy, Dmitry A; Iyevleva, Aglaya G; Bit-Sava, Elena M; Gutkina, Nadezhda I; Anisimenko, Maxim S; Yu Sherina, Nathalia; Mitiushkina, Nathalia V; Ulibina, Yulia M; Yatsuk, Olga S; Zaitseva, Olga A; Suspitsin, Evgeny N; Togo, Alexandr V; Pospelov, Valery A; Kovalenko, Sergey P; Semiglazov, Vladimir F; Imyanitov, Evgeny N

    2009-01-01

    Although the probability of both parents being affected by BRCA1 mutations is not negligible, such families have not been systematically described in the literature. Here we present a large breast-ovarian cancer family, where 3 sisters and 1 half-sister inherited maternal BRCA1 5382insC mutation while the remaining 2 sisters carried paternal BRCA1 1629delC allele. No BRCA1 homozygous mutations has been detected, that is consistent with the data on lethality of BRCA1 knockout mice. This report exemplifies that the identification of a single cancer-predisposing mutation within the index patient may not be sufficient in some circumstances. Ideally, all family members affected by breast or ovarian tumor disease have to be subjected to the DNA testing, and failure to detect the mutation in any of them calls for the search of the second cancer-associated allele. PMID:19338681

  8. Founding BRCA1 mutations in hereditary breast and ovarian cancer in southern Sweden.

    Science.gov (United States)

    Johannsson, O; Ostermeyer, E A; Håkansson, S; Friedman, L S; Johansson, U; Sellberg, G; Brøndum-Nielsen, K; Sele, V; Olsson, H; King, M C; Borg, A

    1996-03-01

    Nine different germ-line mutations in the BRCA1 breast and ovarian cancer susceptibility gene were identified in 15 of 47 kindreds from southern Sweden, by use of SSCP and heteroduplex analysis of all exons and flanking intron region and by a protein-truncation test for exon 11, followed by direct sequencing. All but one of the mutations are predicted to give rise to premature translation termination and include seven frameshift insertions or deletions, a nonsense mutation, and a splice acceptor site mutation. The remaining mutation is a missense mutation (Cys61Gly) in the zinc-binding motif. Four novel Swedish founding mutations were identified: the nucleotide 2595 deletion A was found in five families, the C 1806 T nonsense mutation in three families, the 3166 insertion TGAGA in three families, and the nucleotide 1201 deletion 11 in two families. Analysis of the intragenic polymorphism D17S855 supports common origins of the mutations. Eleven of the 15 kindreds manifesting BRCA1 mutations were breast-ovarian cancer families, several of them with a predominant ovarian cancer phenotype. The set of 32 families in which no BRCA1 alterations were detected included 1 breast-ovarian cancer kindred manifesting clear linkage to the BRCA1 region and loss of the wild-type chromosome in associated tumors. Other tumor types found in BRCA1 mutation/haplotype carriers included prostatic, pancreas, skin, and lung cancer, a malignant melanoma, an oligodendroglioma, and a carcinosarcoma. In all, 12 of 16 kindreds manifesting BRCA1 mutation or linkage contained ovarian cancer, as compared with only 6 of the remaining 31 families (P<.001). The present study confirms the involvement of BRCA1 in disease predisposition for a subset of hereditary breast cancer families often characterized by ovarian cancers.

  9. Founding BRCA1 mutations in hereditary breast and ovarian cancer in southern Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Johannsson, O.; Hakansson, S.; Johannson, U. [Univ. Hospital, Lund (Sweden)] [and others

    1996-03-01

    Nine different germ-line mutations in the BRCA1 breast and ovarian cancer susceptibility gene were identified in 15 of 47 kindreds from southern Sweden, by use of SSCP and heteroduplex analysis of all exons and flanking intron region and by a protein-truncation test for exon 11, followed by direct sequencing. All but one of the mutations are predicted to give rise to premature translation termination and include seven frameshift insertions or deletions, a nonsense mutation, and a splice acceptor site mutation. The remaining mutation is a missense mutation (Cys61Gly) in the zinc-binding motif. Four novel Swedish founding mutations were identified: the nucleotide 2595 deletion A was found in five families, the C 1806 T nonsense mutation in three families, the 3166 insertion TGAGA in three families, and the nucleotide 1201 deletion 11 in two families. Analysis of the intragenic polymorphism D17S855 supports common origins of the mutations. Eleven of the 15 kindreds manifesting BRCA1 mutations were breast-ovarian cancer families, several of them with a predominant ovarian cancer phenotype. The set of 32 families in which no BRCA1 alterations were detected included 1 breast-ovarian cancer kindred manifesting clear linkage to the BRCA1 region and loss of the wild-type chromosome in associated tumors. Other tumor types found in BRCA1 mutation/haplotype carriers included prostatic, pancreas, skin, and lung cancer, a malignant melanoma, an oligodendroglioma, and a carcinosarcoma. In all, 12 of 16 kindreds manifesting BRCA1 mutation or linkage contained ovarian cancer, as compared with only 6 of the remaining 31 families (P < .001). The present study confirms the involvement of BRCA1 in disease predisposition for a subset of hereditary breast cancer families often characterized by ovarian cancers. 28 refs., 3 figs., 4 tabs.

  10. 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

  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.

  12. 76 FR 16431 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-03-23

    ... Committee: National Cancer Institute Special Emphasis Panel; SPORE in Lymphoma, Breast, Ovarian.... 93.392, Cancer Construction; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  13. Genetic counselling and testing for hereditary breast and ovarian cancer: the gent(le) approach.

    Science.gov (United States)

    De Vos, M; Poppe, B; Delvaux, I; Mortier, G; Claes, K; Messiaen, L; De Paepe, A

    1999-10-01

    The counselling experience with 50 Flemish families in whom mutation analysis of the total coding region of the BRCA1 and BRCA2 gene has been initiated, is presented. Genetic testing for breast-ovarian cancer susceptibility is offered by a multidisciplinary team. During the counselling sessions, special attention is given to comprehensible and emotionally acceptable communication of genetic information and to the psychosocial evaluation of the counselee. The limitations of molecular testing and the controversy surrounding cancer prevention strategies are also discussed. The overall acceptance of mutation testing is high. Some of the problems encountered are inaccuracy of the reported family history, poor retrieval of the medical records of affected family members and the reluctance of many patients to inform their relatives about the possibility of being tested.

  14. 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.

  15. 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.

  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. Endometrial Cancer and a Family History of Cancer

    Science.gov (United States)

    Cook, Linda S.; Nelson, Harold E.; Stidley, Christine A.; Dong, Yan; Round, Pamela J.; Amankwah, Ernest K.; Magliocco, Anthony M.; Friedenreich, Christine M.

    2014-01-01

    Objective Lynch Syndrome (LS), an inherited genetic syndrome, predisposes to cancers such as colorectal and endometrial. However, the risk for endometrial cancer (EC) in women not affected by LS, but with a family history of cancer, is currently unknown. We examined the association between a family history of cancer and the risk for EC in non-LS patients. Methods This population-based case-control study included 519 EC cases and 1015 age-matched controls and took place in Alberta, Canada between 2002 and 2006. Information about risk factors, including family history of cancer in first and second degree relatives, was ascertained via in-person interviews. Microsatellite instability (MSI) status of tumor tissue was assessed to determine involvement of DNA mismatch repair genes. Results A first or second degree family history of uterine cancer was modestly associated with the risk for overall EC [odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9,1.9], and the risks were similar for MSI+ cancer (OR= 1.5, 95%CI=0.7, 3.3) and MSI- cancer (OR= 1.3, 95%CI=0.8, 2.4). Although consistent, these associations were modest and not significant. In contrast, the risk for MSI+ cancer was elevated with a reported family history of colorectal cancer (OR= 1.4, 95%CI=1.0, 2.2), but not for MSI- cancer. Conclusions A family history of uterine cancer may be modestly associated with EC risk in non-LS patients regardless of MSI status, suggesting that risk was not related to inherited defects in the MMR gene pathway. These results provide preliminary support for an EC-specific genetic syndrome. PMID:23632205

  18. 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.

  19. 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

  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. RAD51B in Familial Breast Cancer

    DEFF Research Database (Denmark)

    Pelttari, Liisa M; Khan, Sofia; Vuorela, Mikko

    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 RAD......51B 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...

  2. Does Breast or Ovarian Cancer Run in Your Family?

    Science.gov (United States)

    ... Does Breast or Ovarian Cancer Run in Your Family? Language: English Español (Spanish) Recommend on Facebook Tweet ... get ovarian cancer by age 70. Does Your Family Health History Put You At Risk? Collect your ...

  3. Family History of Colon Cancer Calls for Earlier Screening

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_164202.html Family History of Colon Cancer Calls for Earlier Screening ... 2017 (HealthDay News) -- If you've got a family history of colon or rectal cancers, you probably ...

  4. 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.

  5. Proposed Organization of Family Cancer Clinics in Indonesia

    Directory of Open Access Journals (Sweden)

    Kunta Setiaji

    2017-02-01

    Full Text Available Abstract Around 10-15% of breast cancers are associated hereditary and/or familial predisposition. By definition familial breast occurs in two or more first degree relatives within a nuclear pedigree (first or second degree relatives. Hereditary and familial cancer displays different characteristics in the pathological features, clinical course, response to treatment, and outcomes. Therefore, specific consultation and treatment need to be addressed to patients with hereditary or familial predisposition for example the need for rigorous surveillance and preventive treatment including options for preventive surgery. Cancer clinical genetic service is not yet formally available in daily clinical practice in Indonesia. Surgeons usually become the first medical specialist to see cancer patients with familial predisposition, therefore they have to elaborate clinical cancer genetic service under Family Cancer Clinic (FCC. Clinical genetic service within FCC consists of several step-wise tasks including assessment of personal and family history of cancer, personalized cancer risk assessment, review of medical and family history, individual cancer screening and surveillance recommendations, genetic testing if necessary, discussion of benefits and limitations of genetic test, cancer risk reduction options and preventive strategies, and opportunity to participate in research as well as clinical trial. Nation-wide network for FCC is of importance to share knowledge and skill to perform cancer genetic service. Ability to perform genetic test including the interpretation in Indonesia has also been required. Keywords: familial cancer, hereditary cancer, genetic counseling, family cancer clinics

  6. Family Caregivers for Cancer Patients in Thailand

    OpenAIRE

    2013-01-01

    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...

  7. 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.

  8. Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer

    OpenAIRE

    Gara, Sudheer Kumar; Jia, Li; Merino, Maria J.; Agarwal, Sunita K.; Zhang, Lisa; Cam, Maggie; Patel, Dhaval; Kebebew, Electron

    2015-01-01

    Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased HABP2 protein expression in tumor samples from affected family members, as compared with normal adjacent thyroid tissue and samples from sporadic ...

  9. Unique Features of Germline Variation in Five Egyptian Familial Breast Cancer Families Revealed by Exome Sequencing

    Science.gov (United States)

    Kim, Yeong C.; Soliman, Amr S.; Cui, Jian; Ramadan, Mohamed; Hablas, Ahmed; Abouelhoda, Mohamed; Hussien, Nehal; Ahmed, Ola; Zekri, Abdel-Rahman Nabawy; Seifeldin, Ibrahim A.

    2017-01-01

    Genetic predisposition increases the risk of familial breast cancer. Recent studies indicate that genetic predisposition for familial breast cancer can be ethnic-specific. However, current knowledge of genetic predisposition for the disease is predominantly derived from Western populations. Using this existing information as the sole reference to judge the predisposition in non-Western populations is not adequate and can potentially lead to misdiagnosis. Efforts are required to collect genetic predisposition from non-Western populations. The Egyptian population has high genetic variations in reflecting its divergent ethnic origins, and incident rate of familial breast cancer in Egypt is also higher than the rate in many other populations. Using whole exome sequencing, we investigated genetic predisposition in five Egyptian familial breast cancer families. No pathogenic variants in BRCA1, BRCA2 and other classical breast cancer-predisposition genes were present in these five families. Comparison of the genetic variants with those in Caucasian familial breast cancer showed that variants in the Egyptian families were more variable and heterogeneous than the variants in Caucasian families. Multiple damaging variants in genes of different functional categories were identified either in a single family or shared between families. Our study demonstrates that genetic predisposition in Egyptian breast cancer families may differ from those in other disease populations, and supports a comprehensive screening of local disease families to determine the genetic predisposition in Egyptian familial breast cancer. PMID:28076423

  10. 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.

  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. 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.

  13. Proposed Organization of Family Cancer Clinics in Indonesia

    OpenAIRE

    Kunta Setiaji

    2017-01-01

    Abstract Around 10-15% of breast cancers are associated hereditary and/or familial predisposition. By definition familial breast occurs in two or more first degree relatives within a nuclear pedigree (first or second degree relatives). Hereditary and familial cancer displays different characteristics in the pathological features, clinical course, response to treatment, and outcomes. Therefore, specific consultation and treatment need to be addressed to patients with hereditary or familial...

  14. Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer.

    Science.gov (United States)

    Gara, Sudheer Kumar; Jia, Li; Merino, Maria J; Agarwal, Sunita K; Zhang, Lisa; Cam, Maggie; Patel, Dhaval; Kebebew, Electron

    2015-07-30

    Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased HABP2 protein expression in tumor samples from affected family members, as compared with normal adjacent thyroid tissue and samples from sporadic cancers. Functional studies showed that HABP2 has a tumor-suppressive effect, whereas the G534E variant results in loss of function.

  15. Clinical application of family management styles to families of children with cancer.

    Science.gov (United States)

    Ogle, Susan K

    2006-01-01

    The potential clinical application of family management styles for working with families who have children with cancer is discussed. Case studies are used to illustrate the usefulness and clinical application of the model.

  16. 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…

  17. 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,…

  18. Familial testicular cancer in a single-centre population

    NARCIS (Netherlands)

    Sonneveld, DJA; Sleijfer, DT; Sijmons, RH; van der Graaf, WTA; Sluiter, WJ; Hoekstra, HJ; Schraffordt Koops, H.

    1999-01-01

    Familial occurrence of testicular cancer suggests a genetic predisposition to the disease. A genetic susceptibility may also be reflected by the occurrence of bilateral testicular neoplasms and the high rates of urogenital developmental anomalies in families prone to testicular cancer. In this study

  19. 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.

  20. Helping patients and their family caregivers cope with cancer.

    Science.gov (United States)

    Northouse, Laurel L

    2012-09-01

    Family caregivers face multiple demands as they care for their loved ones with cancer, and these demands have increased dramatically in recent years. Patients with cancer now receive toxic treatments in outpatient settings and return home to the care of their family members. Some patients receive in-home infusions, which were unheard of a few years ago. Family caregivers provide tasks that were previously provided by nurses; however, caregivers lack the educational preparation that nurses receive.

  1. PALB2 germline mutations in familial breast cancer cases with personal and family history of pancreatic cancer

    OpenAIRE

    2010-01-01

    PALB2 germline mutations in familial breast cancer cases with personal and family history of pancreatic cancer phone: +39-02-23903224 (Radice, Paolo) (Radice, Paolo) IFOM, Fondazione Istituto FIRC di Oncologia Molecolare - Milan - ITALY (Peterlongo, Paolo) Department of Preventive and Predictive Medicine, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale dei Tumori - Milan - ITALY (Peterlongo, Pao...

  2. 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.

  3. 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.

  4. 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

  5. Immunotherapeutic Vaccine as an Alternative Treatment to Overcome Drug-Resistant Ovarian Cancer

    Science.gov (United States)

    2012-07-01

    cells by polyvalent Listeria monocytogenes-based vaccines. J Immunother 32:856-69. 6. Karkada M, Weir, G.M., Quinton,T., Sammatur, L., MacDonald, L.D...polyva- lent Listeria monocytogenes-based vaccines. J Immunother 2009; 32:856–69. 6 Karkada M, Weir GM, Quinton T et al. A novel breast/ovarian cancer

  6. Systemic treatment for hereditary cancers: a 2012 update.

    Science.gov (United States)

    Imyanitov, Evgeny N; Byrski, Tomasz

    2013-04-01

    The history of specific therapy for hereditary tumors dates back to mid 1980s and involves a number of reports demonstrating regression of familial colon polyps upon administration of sulindac. Virtually no clinical studies on other hereditary cancer types were available until the year 2009, when Byrski et al. presented the data on unprecedented sensitivity of BRCA1-associated breast malignancies to cisplatin. This breakthrough has revived interest to the treatment of cancer in germ-line mutation carriers. Recent trials and clinical observations have confirmed the efficacy of platinating agents and PARP inhibitors in BRCA1/2-driven breast, ovarian and pancreatic carcinomas. Pegylated liposomal doxorubicin may be considered as a promising treatment option for BRCA1/2-related ovarian cancer after the failure of platinum-containing therapy. Several novel drugs have been recently introduced in the management of rare familial tumor syndromes. Vandetanib, a low-molecular weight RET kinase inhibitor, demonstrated substantial efficacy in the treatment of hereditary and sporadic medullary thyroid cancer. Vismodegib, an inhibitor of SMO oncoprotein, caused regression of basal-cell carcinomas in patients with Gorlin syndrome. Down-regulation of mTOR kinase by everolimus has been successfully used for the therapy of subependymal giant-cell astrocytomas in patients with tuberous sclerosis. The achievements in the prevention, diagnostics and treatment of hereditary cancers may serve as an excellent example of triumph of translational medicine.

  7. [CHEK2-mutation in Dutch breast cancer families: expanding genetic testing for breast cancer

    NARCIS (Netherlands)

    Adank, M.A.; Hes, F.J.; Zelst-Stams, W.A.G. van; Tol, M.P. van den; Seynaeve, C.; Oosterwijk, J.C.

    2015-01-01

    - In the majority of breast cancer families, DNA testing does not show BRCA1 or BRCA2 mutations and the genetic cause of breast cancer remains unexplained. - Routine testing for the CHEK2*1100delC mutation has recently been introduced in breast cancer families in the Netherlands. - The 1100delC muta

  8. Family survivorship and quality of life following a cancer diagnosis.

    Science.gov (United States)

    Mellon, S; Northouse, L L

    2001-12-01

    The objectives of this study were: (a) to examine the quality of life of the family as a unit during the long-term survivor phase of illness and (b) to test a family model of factors that may influence family quality of life. The family survivorship model, which includes illness survival stressors (family stressors, fear of recurrence, and patient somatic concerns), resources (family hardiness and family social support), appraisal (family meaning of the illness), and the outcome, family quality of life, was used to guide this exploratory cross-sectional study. A random, stratified sample of 123 families (N = 246 individuals) was interviewed 1-5 years after treatment ended. The model explained 63% of the variance in family quality of life, with the strongest predictors being concurrent family stressors, family social support, family member fear of recurrence, family meaning of the illness, and patient employment status. The study findings suggest the importance of addressing cancer-related stressors, family resources, and family meaning as key factors related to family quality of life.

  9. The impact of cancer in women on the family.

    Science.gov (United States)

    Northouse, L L

    1995-01-01

    Using a family-stress framework, this paper analyzes the psychosocial impact of a woman's cancer on her family. More specifically, this paper explores the emotional distress that spouses and children of patients with breast cancer experience and discusses the role changes that are reported over time. Factors that put certain women and their family members at high risk of poorer adjustment to the woman's cancer also are identified. Finally, directions for future research and the implications of the research for clinical practice are discussed.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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…

  15. 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...

  16. Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands.

    Science.gov (United States)

    Dommering, Charlotte J; Henneman, Lidewij; van der Hout, Annemarie H; Jonker, Marianne A; Tops, Carli M J; van den Ouweland, Ans M W; van der Luijt, Rob B; Mensenkamp, Arjen R; Hogervorst, Frans B L; Redeker, Egbert J W; de Die-Smulders, Christine E M; Moll, Annette C; Meijers-Heijboer, Hanne

    2017-04-01

    Since the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands. Uptake for retinoblastoma (Rb) was compared with uptake for Von Hippel-Lindau disease (VHL), Li-Fraumeni syndrome (LFS), familial adenomatous polyposis (FAP), and hereditary breast ovarian cancer (HBOC). A questionnaire was completed by all nine DNA-diagnostic laboratories assessing the number of independent mutation-positive families identified from the start of diagnostic testing until May 2013, and the number of PNDs performed for these syndromes within these families. Of 187 families with a known Rb-gene mutation, 22 had performed PND (11.8%), this was significantly higher than uptake for FAP (1.6%) and HBOC (<0.2%). For VHL (6.5%) and LFS (4.9%) the difference was not statistically significant. PND for Rb started 3 years after introduction of diagnostic DNA testing and remained stable over the years. For the other cancer syndromes PND started 10-15 years after the introduction and uptake for PND showed an increase after 2009. We conclude that uptake of PND for Rb was significantly higher than for FAP and HBOC, but not different from VHL and LFS. Early onset, high penetrance, lack of preventive surgery and perceived burden of disease may explain these differences.

  17. 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.

  18. Psychologic consequences of breast cancer on partner and family.

    Science.gov (United States)

    Northouse, L L; Cracchiolo-Caraway, A; Appel, C P

    1991-08-01

    Breast cancer can have psychologic consequences not only for patients but also for the entire family system. Research indicates a major impact on the husband, the marital relationship, the children, and family roles and responsibilities. Greater attention needs to be given to the family members to ensure that they get the support they need, and to enable them to maintain their supportive roles with the patient.

  19. 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.

  20. 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…

  1. The Smad family and its role in pancreatic cancer.

    Science.gov (United States)

    Singh, P; Wig, J D; Srinivasan, R

    2011-01-01

    One of the major signaling pathways that determine the tumor aggression and patient outcome in pancreatic cancer is the transforming growth factor-beta (TGF-ß) pathway. It is inactivated at various levels in pancreatic cancer and plays a dual role in tumor initiation and progression. The Smad family of proteins transduce signals from the TGF-ß superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. This review discusses the structure, function and regulation of various participating Smad family members, and their individual roles in determining the progression and outcome of pancreatic cancer patients, with a special emphasis on Smad4.

  2. Family Support and Colorectal Cancer Screening among Urban African Americans.

    Science.gov (United States)

    Brittain, Kelly; Taylor, Jacquelyn Y; Loveland-Cherry, Carol; Northouse, Laurel; Caldwell, Cleopatra H

    2012-07-01

    Colorectal cancer (CRC) is the third leading cause of cancer death among African Americans. Less than 50% of African Americans have had CRC screening. This study examined the relationships between family support and influence, cultural identity, CRC beliefs, and a screening informed decision among 129 urban African Americans. Family support (p < .01) significantly predicted CRC beliefs and CRC beliefs significantly predicted informed decision (p < .01). Based on study results, practitioners should routinely assess family support and CRC beliefs with African Americans patients. This may improve patient-provider shared decision-making satisfaction and CRC screening adherence among African American patients.

  3. The rationale for targeting the LOX family in cancer.

    Science.gov (United States)

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

    2012-07-19

    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 subject of much effort to understand their roles in cancer. In this Review we discuss the roles of members of this family in the remodelling of the tumour microenvironment and their paradoxical roles in tumorigenesis and metastasis. We also discuss how targeting this family of proteins might lead to a new avenue of cancer therapeutics.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Receptivity and preferences of pancreatic cancer family members for participating in lifestyle programs to reduce cancer risk

    OpenAIRE

    Howell, Lisa A.; Sinicrope, Pamela S.; Brockman, Tabetha A.; Patten, Christi A.; Decker, Paul A; Ehlers, Shawna L.; Nadeau, Ashley; Rabe, Kari G.; Breitkopf, Carmen Radecki; Gloria M Petersen

    2013-01-01

    Background Cancer is a shared family experience that might provide an opportunity for lifestyle change among at-risk family members. The purpose of this study was to assess receptivity and preferences for cancer risk reduction programs among at-risk family members with two or more relatives affected with pancreas cancer. Methods We surveyed 401 at-risk family members in an existing pancreatic cancer family registry. Participants completed a mailed survey which examined demographic, medical, a...

  9. Assessing needs of family members of inpatients with advanced cancer.

    Science.gov (United States)

    Bužgová, R; Špatenková, N; Fukasová-Hajnová, E; Feltl, D

    2016-07-01

    To provide high-quality and effective cancer care, problems and unmet needs of family members during their relatives' hospitalisation have to be identified as well. The aims were to determine how needs of family members of patients with terminal cancer are met and to analyse factors that influence them. The needs were assessed with the Family Inventory of Needs. Each item (n = 20) represents one need of family members, for which the importance and satisfaction are rated. The study comprised 270 family members of hospitalised advanced cancer patients staying in the University Hospital Ostrava who were receiving palliative care. The family members preferred sufficient basic information and patient comfort. The unmet needs were support of hope (73%) and provision of information (65%). The unmet needs were more frequently identified by women, individuals with lower education, younger persons, unemployed, patients' children and family members of patients with generally unfavourable health status (P family members may improve their quality of life.

  10. Resilience in families with a child with cancer.

    Science.gov (United States)

    Greeff, Abraham Petrus; Vansteenwegen, Alfons; Geldhof, Annelies

    2014-10-01

    The aim of this study was to identify and explore resilience factors associated with family adaption after a child had been diagnosed with cancer. Using a cross-sectional survey research design, parents (n = 26), and children (n = 25) from the same families independently completed six self-report questionnaires, as well as responded to an open-ended question about those qualities that helped their family through the period following the diagnosis. The most significant results came from the children's data. According to these results, connectedness within the family, the experience of control over life events, family routines, positive, and supportive communication, redefinition of crisis situations, and lastly, a passive appraisal of crisis situations, were positively linked to better family adaptation. The identified factors should be strengthened and developed in families finding themselves in a similar situation.

  11. Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay

    Science.gov (United States)

    Baert, Annelot; Depuydt, Julie; Van Maerken, Tom; Poppe, Bruce; Malfait, Fransiska; Van Damme, Tim; De Nobele, Sylvia; Perletti, Gianpaolo; De Leeneer, Kim; Claes, Kathleen B.M.; Vral, Anne

    2017-01-01

    Breast cancer risk drastically increases in individuals with a heterozygous germline BRCA1 or BRCA2 mutation, while it is estimated to equal the population risk for relatives without the familial mutation (non-carriers). The aim of the present study was to use a G2 phase-specific micronucleus assay to investigate whether lymphocytes of healthy BRCA2 mutation carriers are characterized by increased radiosensitivity compared to controls without a family history of breast/ovarian cancer and how this relates to healthy non-carrier relatives. BRCA2 is active in homologous recombination, a DNA damage repair pathway, specifically active in the late S/G2 phase of the cell cycle. We found a significantly increased radiosensitivity in a cohort of healthy BRCA2 mutation carriers compared to individuals without a familial history of breast cancer (P=0.046; Mann-Whitney U test). At the individual level, 50% of healthy BRCA2 mutation carriers showed a radiosensitive phenotype (radiosensitivity score of 1 or 2), whereas 83% of the controls showed no radiosensitivity (P=0.038; one-tailed Fishers exact test). An odds ratio of 5 (95% CI, 1.07–23.47) indicated an association between the BRCA2 mutation and radiosensitivity in healthy mutation carriers. These results indicate the need for the gentle use of ionizing radiation for either diagnostic or therapeutic use in BRCA2 mutation carriers. We detected no increased radiosensitivity in the non-carrier relatives. PMID:28184943

  12. 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.

  13. Family rituals, financial burden, and mothers' adjustment in pediatric cancer.

    Science.gov (United States)

    Santos, Susana; Crespo, Carla; Canavarro, M Cristina; Alderfer, Melissa A; Kazak, Anne E

    2016-12-01

    The financial burden of childhood cancer may contribute to the distress that parents experience during and after treatment. Inconsistent relationships between financial burden and parental psychological distress highlight the need to identify psychosocial factors that may moderate this relationship. In this study, we aimed to determine if family ritual meaning moderates the relationship between financial burden and anxiety and depression symptoms among mothers of children with cancer. Portuguese mothers of children with cancer on-treatment and off-treatment (N = 244) completed measures of financial burden, anxiety and depression symptoms, and family ritual meaning. Moderating effects were tested using hierarchical multiple regression analyses. Family ritual meaning buffered the effect of financial burden on anxiety, but not on depression symptoms. The relationship between financial burden and anxiety symptoms was not significant when mothers endorsed higher levels of family ritual meaning. Although preliminary, the current findings suggest that high levels of perceived family ritual meaning may constitute a protective factor against the effect of financial burden on mothers' anxiety symptoms. Promoting family ritual meaning might be an effective approach to reducing anxiety symptoms of mothers of children with cancer in the context of financial burden. (PsycINFO Database Record

  14. BARD1 variants are not associated with breast cancer risk in Australian familial breast cancer.

    Science.gov (United States)

    Gorringe, Kylie L; Choong, David Y H; Visvader, Jane E; Lindeman, Geoffrey J; Campbell, Ian G

    2008-10-01

    Several studies in various populations have suggested that non-synonymous BARD1 variants are associated with increased breast cancer risk. Using DHPLC analysis we screened the coding region of BARD1 for variants in 210 probands of breast cancer families including 129 families with no mutations in BRCA1 or BRCA2. These families were ascertained in Australia through the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). Nine coding variants were detected among the kConFab families, including two novel variants (Thr598Ile and Ile692Thr). The frequency of five of these variants were evaluated in 258 non-cancer controls and 401 women with sporadic breast cancer. Three variants (1139del21, G1756C and A2285G) were detected in all three groups at a similar frequency suggesting that these do not represent BRCAX candidates. Two variants (Thr598Ile and Ile692Thr) were not detected in any of the 659 sporadic breast cancer cases and controls and were assessed for segregation with breast cancer in the families of the probands. However, neither variant was identified in any other breast cancer case in either family suggesting that these variants are non-pathogenic polymorphisms. We have found no evidence to support involvement of BARD1 in familial breast cancer risk in the Australian population. In addition, three variants previously reported to be pathogenic in other populations are likely to represent benign polymorphisms and therefore we conclude that BARD1 is unlikely to represent a high-penetrance breast cancer susceptibility gene.

  15. 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.

  16. 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.

  17. Variation in the RAD51 gene and familial breast cancer

    Science.gov (United States)

    Lose, Felicity; Lovelock, Paul; Chenevix-Trench, Georgia; Mann, Graham J; Pupo, Gulietta M; Spurdle, Amanda B

    2006-01-01

    Introduction Human RAD51 is a homologue of the Escherichia coli RecA protein and is known to function in recombinational repair of double-stranded DNA breaks. Mutations in the lower eukaryotic homologues of RAD51 result in a deficiency in the repair of double-stranded DNA breaks. Loss of RAD51 function would therefore be expected to result in an elevated mutation rate, leading to accumulation of DNA damage and, hence, to increased cancer risk. RAD51 interacts directly or indirectly with a number of proteins implicated in breast cancer, such as BRCA1 and BRCA2. Similar to BRCA1 mice, RAD51-/- mice are embryonic lethal. The RAD51 gene region has been shown to exhibit loss of heterozygosity in breast tumours, and deregulated RAD51 expression in breast cancer patients has also been reported. Few studies have investigated the role of coding region variation in the RAD51 gene in familial breast cancer, with only one coding region variant – exon 6 c.449G>A (p.R150Q) – reported to date. Methods All nine coding exons of the RAD51 gene were analysed for variation in 46 well-characterised, BRCA1/2-negative breast cancer families using denaturing high-performance liquid chromatography. Genotyping of the exon 6 p.R150Q variant was performed in an additional 66 families. Additionally, lymphoblastoid cell lines from breast cancer patients were subjected to single nucleotide primer extension analysis to assess RAD51 expression. Results No coding region variation was found, and all intronic variation detected was either found in unaffected controls or was unlikely to have functional consequences. Single nucleotide primer extension analysis did not reveal any allele-specific changes in RAD51 expression in all lymphoblastoid cell lines tested. Conclusion Our study indicates that RAD51 is not a major familial breast cancer predisposition gene. PMID:16762046

  18. PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines.

    Directory of Open Access Journals (Sweden)

    Teruki Yanagi

    Full Text Available While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL. Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells.

  19. GPs' management of women seeking help for familial breast cancer

    NARCIS (Netherlands)

    de Bock, GH; Vlieland, TPMV; Hakkeling, M; Kievit, J; Springer, MP

    1999-01-01

    Objective. We aimed to ascertain how often patients seek help for familial breast cancer in primary care, and to identify GPs management of these patients, in order to see whether guidelines are followed. Methods. This was a descriptive study. GPs (n = 202) attending a postgraduate education program

  20. 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.

  1. PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines.

    Science.gov (United States)

    Yanagi, Teruki; Shi, Ranxin; Aza-Blanc, Pedro; Reed, John C; Matsuzawa, Shu-ichi

    2015-01-01

    While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL). Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells.

  2. Activating mutation in MET oncogene in familial colorectal cancer

    Directory of Open Access Journals (Sweden)

    Schildkraut Joellen M

    2011-10-01

    Full Text Available Abstract Background In developed countries, the lifetime risk of developing colorectal cancer (CRC is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The MET proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility. Methods MET exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies. Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C >T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors. Results Here we report a germline non-synonymous change in the MET proto-oncogene at amino acid position T992I (also reported as MET p.T1010I in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in Conclusions Although the MET p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this MET genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will

  3. 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.

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

    OpenAIRE

    Vogelaar Ingrid P; van der Post Rachel S; Bisseling Tanya M; van Krieken J Han JM; Ligtenberg Marjolijn JL; Hoogerbrugge Nicoline

    2012-01-01

    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. ...

  5. The Smad family and its role in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    P Singh

    2011-01-01

    Full Text Available One of the major signaling pathways that determine the tumor aggression and patient outcome in pancreatic cancer is the transforming growth factor-beta (TGF-ß pathway. It is inactivated at various levels in pancreatic cancer and plays a dual role in tumor initiation and progression. The Smad family of proteins transduce signals from the TGF-ß superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. This review discusses the structure, function and regulation of various participating Smad family members, and their individual roles in determining the progression and outcome of pancreatic cancer patients, with a special emphasis on Smad4.

  6. 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

  7. 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.

  8. [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.

  9. BRCA1 Gene Mutations in Chinese Families with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Yurong Shi; Chenbin Li; Ruifang Niu; Xishan Hao; Xiangcheng Zhi; Liansheng Ning

    2005-01-01

    OBJECTIVE To investigate the frequency of BRCA1 gene mutations in breast cancer families in China.METHODS Genomic DNA was obtained by conventional techniques from the peripheral blood mononuclear cells collected from 94 persons derived from 45 breast cancer families. All participants gave written informed consent. The mutations in the BRCA1 gene were detected by the polymerase chain reaction and single stranded conformation polymorphism(PCR-SSCP). Then , the samples of interest were sent for direct DNA sequencing.RESULTS No mutation sites were found in exon 2 or 20 by DNA sequencing.Eight sites were found in exon 11 such as 2201C>T (Ser694Ser),3232A>G(Glu 1038Gly), 2201C >A/G (Ser694Arg), 2731C >T (Pro871Leu),2086A >T(Asn591lle) and three sites of 1584G>T (Glu424Stop). Three mutation sites were found in exon 16 which included 5106A >G (Met1663Val),5208delT(Stop 1639) and 4956A>G (Ser 1613Gly).CONCLUSION These mutation sites may be related to breast cancer, but more investigation is needed to determine whether the mutation sites are hot spots of mutations in Chinese familial breast cancer patients.

  10. STAT-3 inhibitors: state of the art and new horizons for cancer treatment.

    Science.gov (United States)

    Lavecchia, A; Di Giovanni, C; Novellino, E

    2011-01-01

    The signal transducers and activators of transcription (STATs) include a class of cytoplasmic signaling proteins whose role in the regulation of cell growth and survival is mediated by phosphorylation of a critical tyrosine residue within the STAT protein. This occurs in response to cytokines and growth factors modulating the expression of specific target genes. In particular, phosphorylation induces STAT:STAT dimer formation between two monomers, via reciprocal phosphoTyr (pTyr)-SH2 domain interactions. To date, seven members of the STAT family, all with different roles, have been identified in mammals. After dimerization, phosphorylated STATs enter the nucleus and, working co-ordinately with other transcriptional co-activators and transcription factors, induce increased transcriptional initiation. In healthy human and animal cells, ligand-dependent activation of STATs is a transient process, lasting for several minutes to several hours. In contrast, in many cancerous cell lines and tumors, where growth factor dysregulation is frequently at the heart of cellular transformation, the STAT proteins (in particular STAT1, 3 and 5) are persistently tyrosine-phosphorylated or activated; abnormal levels of STAT3 activation have been observed in breast, ovarian, prostate, hematological and head and neck cancer cell lines. Thus, in this review, we examine the most important classes of agents designed to disrupt STAT3 signaling, with particular regard to STAT3 dimerization inhibitors, which could play a significant role in the future of cancer and adjuvant cancer therapies.

  11. LINE-1 methylation is inherited in familial testicular cancer kindreds

    Directory of Open Access Journals (Sweden)

    Gadalla Shahinaz M

    2010-05-01

    Full Text Available Abstract Background Testicular germ cell tumors (TGCT are the most frequent cancers among young men. There is a clear familial component to TGCT etiology, but no high-penetrance susceptibility gene has been identified. Epigenetic aberrations of the genome represent an alternative mechanism for cancer susceptibility; and, studies suggest that epigenetic changes that influence cancer risk can be inherited through the germline. Global DNA hypomethylation has been associated with the risk of cancers of the bladder and head/neck. Methods We performed a pilot study of global methylation at long interspersed nuclear elements-1 (LINE-1 in peripheral blood DNA isolated from 466 family members of 101 multiple-case testicular cancer families. Results Investigating the correlation of LINE-1 methylation levels among parent-child pairs independent of affection status (n = 355 revealed a strong positive association only between mother-daughter (r = 0.48, P = r = 0.31, P = 0.02, suggesting gender-specific inheritance of methylation. Incorporating cancer status, we observed a strong correlation in LINE-1 methylation levels only among affected father-affected son pairs (r = 0.49, P = 0.03. There was a marginally significant inverse association between lower LINE-1 methylation levels and increased TGCT risk, compared with healthy male relatives (P = 0.049. Conclusions Our data suggest that heritability of LINE-1 methylation may be gender-specific. Further, the strong correlation between LINE-1 methylation levels among affected father-affected son pairs suggests that transgenerational inheritance of an epigenetic event may be associated with disease risk. Larger studies are needed to clarify these preliminary observations.

  12. The Needs of Family Members of Cancer Patients

    Science.gov (United States)

    1988-01-01

    Northouse studied post mastectomy patients and their fear of recurrence. The study consisted of 30 women between the ages of 37-74 who had a mastectomy...Counseling and Health Education, 4(1), 36-39. Northouse , L.L. (1981). Mastectomy patients and the fear of recurrence. Cancer Nursing, 4(3), 213-220... Northouse , L.L. (1984). The impact of cancer on the family: an overview. International Journal of Psychiatry, 14(3), 215-242. O’Brien, M.E. (1983). An

  13. Genetic risk transmission in a family affected by familial breast cancer.

    Science.gov (United States)

    Pilato, Brunella; De Summa, Simona; Danza, Katia; Lacalamita, Rosanna; Lambo, Rossana; Sambiasi, Domenico; Paradiso, Angelo; Tommasi, Stefania

    2014-01-01

    Breast Cancer is the most common malignancy among women. Family history is the strongest single predictor of breast cancer risk, and thus great attention has been focused on BRCA1 and BRCA2 genes whose mutations lead to a high risk of developing this disease. Today, only 25% of high- and moderate-risk genes are known, suggesting the importance of the discovery of new risk modifiers. Therefore, the investigation of new polygenic alterations is of great importance, especially if considered high- and moderate-risk variants. In this study, the transmission of BRCA1-2 polymorphisms in association with the transmission of polymorphisms in the genes NUMA1, CCND1, COX11, FGFR2, TNRC9 and SLC4A7 were examined in all members of a family with the BRCA2 c.6447_6448dup mutation. This is the first study about the transmission of high-risk polygenic variants in all members of a family with a strong history of breast cancer. The results about the possible polygenic variant associations that could increase and modify the risk suggested the importance to search new variants to better manage patients and their family members.

  14. 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.

  15. Communication and technology in genetic counseling for familial cancer.

    Science.gov (United States)

    Lynch, H T; Snyder, C; Stacey, M; Olson, B; Peterson, S K; Buxbaum, S; Shaw, T; Lynch, P M

    2014-03-01

    When a cancer predisposing germline mutation is detected in an index case, the presence of the underlying syndrome is confirmed and the potential for predictive testing of at-risk relatives is established. However, the reporting of a positive family history does not routinely lead to communication of information about risk to close, much less distant relatives. This review summarizes information technology utilized to address penetration or 'reach' of knowledge of risk within extended families, including the use of telephone and video counseling to reach distant patients, and anticipate novel internet-based processes for communication between investigators and relatives.

  16. Distinct Gene Expression Signatures in Lynch Syndrome and Familial Colorectal Cancer Type X

    DEFF Research Database (Denmark)

    Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas;

    2013-01-01

    Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....

  17. Cancer Worry, Perceived Risk and Cancer Screening in First-Degree Relatives of Patients with Familial Gastric Cancer.

    Science.gov (United States)

    Li, Jenny; Hart, Tae L; Aronson, Melyssa; Crangle, Cassandra; Govindarajan, Anand

    2016-06-01

    Currently, there is a lack of evidence evaluating the psychological impact of cancer-related risk perception and worry in individuals at high risk for gastric cancer. We examined the relationships between perceived risk, cancer worry and screening behaviors among first-degree relatives (FDRs) of patients with familial gastric cancer. FDRs of patients diagnosed with familial gastric cancer with a non-informative genetic analysis were identified and contacted. Participants completed a telephone interview that assessed socio-demographic information, cancer risk perception, cancer worry, impact of worry on daily functioning, and screening behaviors. Twenty-five FDRs completed the telephone interview. Participants reported high levels of comparative and absolute cancer risk perception, with an average perceived lifetime risk of 54 %. On the other hand, cancer-related worry scores were low, with a significant minority (12 %) experiencing high levels of worry. Study participants exhibited high levels of confidence (median = 70 %) in the effectiveness of screening at detecting a curable cancer. Participants that had undergone screening in the past showed significantly lower levels of cancer-related worry compared to those that had never undergone screening. In conclusion, individuals at high-risk for gastric cancer perceived a very high personal risk of cancer, but reported low levels of cancer worry. This paradoxical result may be attributed to participants' high levels of confidence in the effectiveness of screening. These findings highlight the importance for clinicians to discuss realistic risk appraisals and expectations towards screening with unaffected members of families at risk for gastric cancer, in an effort to help mitigate anxiety and help with coping.

  18. 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

    . Data in the Danish HNPCC register on the frequency and lifetime risk of gynecologic cancers were analyzed and the actual surveillance strategy discussed in relation to the results. DESIGN: Register-based retrospective study. METHOD: A total of 1,780 at-risk women were identified and epidemiological...... of ovarian cancer were identified with a lifetime risk of three to four times the general population. No significant correlation was found between the frequency of ovarian cancer and MMR gene mutation status in the families. CONCLUSION: The benefit of surveillance concerning gynecological cancers seems...

  19. The IL-2 cytokine family in cancer immunotherapy.

    Science.gov (United States)

    Sim, Geok Choo; Radvanyi, Laszlo

    2014-08-01

    The use of cytokines from the IL-2 family (also called the common γ chain cytokine family) such as interleukin (IL)-2, IL-7, IL-15, and IL-21 to activate the immune system of cancer patients is one of the most important areas of current cancer immunotherapy research. The infusion of IL-2 at low or high doses for multiple cycles in patients with metastatic melanoma and renal cell carcinoma was the first successful immunotherapy for cancer proving that the immune system could completely eradicate tumor cells under certain conditions. The initial clinical success observed in some IL-2-treated patients encouraged further efforts focused on developing and improving the application of other IL-2 family cytokines (IL-4, IL-7, IL-9, IL-15, and IL-21) that have unique biological effects playing important roles in the development, proliferation, and function of specific subsets of lymphocytes at different stages of differentiation with some overlapping effects with IL-2. IL-7, IL-15, and IL-21, as well as mutant forms or variants of IL-2, are now also being actively pursued in the clinic with some measured early successes. In this review, we summarize the current knowledge on the biology of the IL-2 cytokine family focusing on IL-2, IL-15 and IL-21. We discuss the similarities and differences between the signaling pathways mediated by these cytokines and their immunomodulatory effects on different subsets of immune cells. Current clinical application of IL-2, IL-15 and IL-21 either as single agents or in combination with other biological agents and the limitation and potential drawbacks of these cytokines for cancer immunotherapy are also described. Lastly, we discuss the future direction of research on these cytokines, such as the development of new cytokine mutants and variants for improving cytokine-based immunotherapy through differential binding to specific receptor subunits.

  20. Screening and surveillance approaches in familial pancreatic cancer.

    Science.gov (United States)

    Canto, Marcia Irene

    2008-07-01

    Screening and surveillance for pancreatic cancer and its precursors is a relatively new indication for endoscopic ultrasound. It provides an alternative approach to the ineffective treatment of mostly incurable symptomatic pancreatic cancer. It is currently reserved for individuals with an increased risk for pancreatic ductal adenocarcinoma, such as those who have inherited genetic syndromes (eg, patients who have Peutz-Jeghers syndrome or hereditary pancreatitis, germline mutation carriers of p16 and BRCA2) and at-risk relatives of patients who have familial pancreatic cancer. This article discusses the rationale for performing screening and surveillance, the types of patients who are eligible for screening, the diagnostic modalities and technique for screening, the diagnostic yield of screening, and the ongoing research.

  1. A diagnostic dilemma following risk-reducing surgery for BRCA1 mutation – a case report of primary papillary serous carcinoma presenting as sigmoid cancer

    Directory of Open Access Journals (Sweden)

    Nash Guy F

    2007-09-01

    Full Text Available Abstract Background Women that carry germ-line mutations for BRCA1 or BRCA2 genes are at an increased risk of developing breast, ovarian and peritoneal cancer. Primary peritoneal carcinoma is a rare tumour histologically identical to papillary serous ovarian carcinoma. Risk-reducing surgery in the form of mastectomy and oophorectomy in premenopausal women has been recommended to prevent breast and ovarian cancer occurrence and decrease the risk of developing primary peritoneal cancer. Case presentation We present a case report of a woman with a strong family history of breast cancer who underwent risk-reducing surgery in the form of bilateral salpingo-oophorectomy following a mastectomy for a right-sided breast tumour. Following the finding of a BRCA1 mutation, a prophylactic left-sided mastectomy was performed. After remaining well for twenty-seven years, she presented with rectal bleeding and altered bowel habit, and was found to have a secondary cancer of the sigmoid colon. She was finally diagnosed with primary papillary serous carcinoma of the peritoneum (PSCP. Conclusion PSCP can present many years after risk-reducing surgery and be difficult to detect. Surveillance remains the best course of management for patients with known BRCA mutations.

  2. Cancer Communication and Family Caregiver Quality of Life

    Science.gov (United States)

    Wittenberg, Elaine; Borneman, Tami; Koczywas, Marianna; Del Ferraro, Catherine; Ferrell, Betty

    2017-01-01

    Family caregivers have enormous communication responsibilities tied to caregiving, such as sharing the patient’s medical history with providers, relaying diagnosis and prognosis to other family members, and making decisions about care with the patient. While caregiver stress and burden has been widely documented in the caregiving literature, little is known about how communication burden, real or perceived communication challenges, impacts caregiver quality of life. In family caregiving, the City of Hope (COH) Quality of Life model proposes that the caregiving experience is reciprocal to the patient experience, impacting physical, social, psychological, and spiritual quality of life. We used data from a pilot study testing a communication coaching call intervention with family caregivers of lung cancer patients to analyze caregiver reported communication burden and quality of life. We found variances in each quality of life domain, suggesting that caregiver interventions should range from self-care skill building for physical care to psycho-educational interventions that support caregiver coping and communication skill building. These findings demonstrate the importance of caregiver assessment and attention to communication burden in quality cancer care. PMID:28257110

  3. Cancer Communication and Family Caregiver Quality of Life

    Directory of Open Access Journals (Sweden)

    Elaine Wittenberg

    2017-03-01

    Full Text Available Family caregivers have enormous communication responsibilities tied to caregiving, such as sharing the patient’s medical history with providers, relaying diagnosis and prognosis to other family members, and making decisions about care with the patient. While caregiver stress and burden has been widely documented in the caregiving literature, little is known about how communication burden, real or perceived communication challenges, impacts caregiver quality of life. In family caregiving, the City of Hope (COH Quality of Life model proposes that the caregiving experience is reciprocal to the patient experience, impacting physical, social, psychological, and spiritual quality of life. We used data from a pilot study testing a communication coaching call intervention with family caregivers of lung cancer patients to analyze caregiver reported communication burden and quality of life. We found variances in each quality of life domain, suggesting that caregiver interventions should range from self-care skill building for physical care to psycho-educational interventions that support caregiver coping and communication skill building. These findings demonstrate the importance of caregiver assessment and attention to communication burden in quality cancer care.

  4. Genetic Alterations in Familial Breast Cancer: Mapping and Cloning Genes Other Than BRCAl

    Science.gov (United States)

    1997-09-01

    predispose to breast cancer . These mutations are always in the context of Cowden’s Syndrome, and do not appear in families with brest cancer in the...AD AWARD NUMBER DAMD17-94-J-4307 TITLE: Genetic Alterations in Familial Breast Cancer : Mapping and Cloning Genes Other Than BRCA1 PRINCIPAL...Aug97-) Genetic Alterations in Familial Breast Cancer : Mapping and Cloning Genes Other than BRCA1 6. AUTHOR{S) Mary-Clair King, Ph.D. 7

  5. CDC Grand Rounds: Family History and Genomics as Tools for Cancer Prevention and Control.

    Science.gov (United States)

    Rodriguez, Juan L; Thomas, Cheryll C; Massetti, Greta M; Duquette, Debra; Avner, Lindsay; Iskander, John; Khoury, Muin J; Richardson, Lisa C

    2016-11-25

    Although many efforts in cancer prevention and control have routinely focused on behavioral risk factors, such as tobacco use, or on the early detection of cancer, such as colorectal cancer screening, advances in genetic testing have created new opportunities for cancer prevention through evaluation of family history and identification of cancer-causing inherited mutations. Through the collection and evaluation of a family cancer history by a trained health care provider, patients and families at increased risk for a hereditary cancer syndrome can be identified, referred for genetic counseling and testing, and make informed decisions about options for cancer risk reduction (1). Although hereditary cancers make up a small proportion of all cancers, the number of affected persons can be large, and the level of risk among affected persons is high. Two hereditary cancer syndromes for which public health professionals have worked to reduce the burden of morbidity and mortality are hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome.

  6. 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

  7. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available BACKGROUND: With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical. METHODS AND FINDINGS: We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses. CONCLUSIONS: Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive

  8. 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.

  9. Factors influencing the attitudes of Chinese cancer patients and their families toward the disclosure of a cancer diagnosis.

    Science.gov (United States)

    Sun, Wenwen; Wang, Zhehai; Fang, Shu; Li, Minmin

    2015-03-01

    The disclosure of a cancer diagnosis to patients has been a core topic in oncology departments. Previous studies have demonstrated that Chinese cancer patients and their families differ in their attitudes toward cancer diagnosis disclosure. However, the influencing factors regarding their different attitudes remain unknown. In the present study, a questionnaire was delivered to 266 cancer patients and 266 matched family members. The results showed that cancer patients were more likely to desire to be informed of their condition than family members (85 vs. 18%, P cancer, 16.5% expected to reduce the severity of their condition, and 4.9% expected to lengthen their lives. Therefore, physicians have a responsibility to appropriately provide knowledge regarding cancer to the patients' families if their educational level is lower and if they have no knowledge of recent treatments, which may improve their acceptability of a cancer diagnosis for patients.

  10. Spiritual needs of patients with cancer and family caregivers.

    Science.gov (United States)

    Taylor, Elizabeth Johnston

    2003-08-01

    The purpose of this descriptive, cross-sectional, qualitative study was to describe the spiritual needs experienced in living with cancer from the perspective of patients with cancer and family caregivers. The sample included 28 African American and Euro-American patients with cancer and family caregivers receiving care from inpatient and outpatient units at two metropolitan hospitals in the southwestern United States. In-depth, tape-recorded, semistructured interviews were analyzed using the process of data reduction, data display, and verification. Seven categories of identified spiritual needs included needs associated with relating to an Ultimate Other; the need for positivity, hope, and gratitude; the need to give and receive love; the need to review beliefs, the need to have meaning; and needs related to religiosity and preparation for death. Informants responded with varying levels of awareness of personal spiritual needs. Caregivers were observed to have spiritual needs similar to those of patients. The findings of this study will inform nurses as they assess and document spiritual needs.

  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. Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families.

    Science.gov (United States)

    Muranen, Taru A; Mavaddat, Nasim; Khan, Sofia; Fagerholm, Rainer; Pelttari, Liisa; Lee, Andrew; Aittomäki, Kristiina; Blomqvist, Carl; Easton, Douglas F; Nevanlinna, Heli

    2016-08-01

    The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breast cancer families. We studied the association between breast cancer risk and a PRS based on 75 common genetic variants in 52 Finnish breast cancer families including 427 genotyped women and pedigree information on ~4000 additional individuals by comparing the affected to healthy family members, as well as in a case-control dataset comprising 1272 healthy population controls and 1681 breast cancer cases with information on family history. Family structure was summarized using the BOADICEA risk prediction model. The PRS was associated with increased disease risk in women with family history of breast cancer as well as in women within the breast cancer families. The odds ratio (OR) for breast cancer within the family dataset was 1.55 [95 % CI 1.26-1.91] per unit increase in the PRS, similar to OR in unselected breast cancer cases of the case-control dataset (1.49 [1.38-1.62]). High PRS-values were informative for risk prediction in breast cancer families, whereas for the low PRS-categories the results were inconclusive. The PRS is informative in women with family history of breast cancer and should be incorporated within pedigree-based clinical risk assessment.

  13. 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…

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

    DEFF Research Database (Denmark)

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

    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...... population b) about 33,000 patients diagnosed with cancer in 2007, and c) about 220,000 patients living with a previous diagnosis of cancer.        Results: Data for the total population is known. The total number of contacts with FP in daytime is about 38.4 million, with out of hours service about 2...

  15. 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 ...

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Development and validation of a simple questionnaire for the identification of hereditary breast cancer in primary care

    Directory of Open Access Journals (Sweden)

    Palmero Edenir I

    2009-08-01

    Full Text Available Abstract Background Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult. Methods A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined. Results Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5–26.2 had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65. Conclusion A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at

  1. Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China

    Directory of Open Access Journals (Sweden)

    Goldstein Alisa

    2009-08-01

    Full Text Available Abstract Background Family history (FH by different relative types and risk of upper gastrointestinal (UGI cancers has been only rarely reported; the data on UGI cancer survival are sparse. Methods 600 esophageal squamous cell carcinoma (ESCC cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs and 95% confidence intervals (CIs from logistic regressions, and hazard ratios (HRs from Cox proportional hazard regressions were estimated. Results Increased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.39–2.12, FH of any UGI cancer (OR = 2.28, 95%CI = 1.77–2.95 and FH of esophageal cancer (OR = 2.84, 95%CI = 2.09–3.86, but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.01–3.29. Conclusion These data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis.

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

    Science.gov (United States)

    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 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, breast, and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe, and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling, or child was associated with increased risk of pancreatic cancer (multivariate-adjusted OR = 1.76, 95% CI 1.19–2.61). A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI 0.52–1.31), breast cancer (OR = 1.21, 95% CI 0.97–1.51), or colorectal cancer (OR = 1.17, 95% CI 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study. PMID:20049842

  3. 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

    with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin......IMPORTANCE: Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. OBJECTIVE: To estimate familial risk and heritability of cancer types in a large twin cohort. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 80,309 monozygotic......,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk...

  4. 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.

  5. Family history of cancer, personal history of medical conditions and risk of oral cavity cancer in France: the ICARE study.

    OpenAIRE

    Radoï, Loredana; Paget-Bailly, Sophie; Guida, Florence; Cyr, Diane; Menvielle, Gwenn; Schmaus, Annie; Carton, Matthieu; Cénée, Sylvie; Sanchez, Marie; Guizard, Anne-Valérie; Trétarre, Brigitte; Stücker, Isabelle; Luce, Danièle

    2013-01-01

    International audience; BACKGROUND: The aim of this study was to evaluate the role of family history of cancer and personal history of other medical conditions in the aetiology of the oral cavity cancer in France. METHODS: We used data from 689 cases of oral cavity squamous cell carcinoma and 3481 controls included in a population-based case--control study, the ICARE study. Odds-ratios (ORs) associated with family history of cancer and personal medical conditions and their 95% confidence inte...

  6. Estimating successive cancer risks in Lynch Syndrome families using a progressive three-state model.

    Science.gov (United States)

    Choi, Yun-Hee; Briollais, Laurent; Green, Jane; Parfrey, Patrick; Kopciuk, Karen

    2014-02-20

    Lynch Syndrome (LS) families harbor mutated mismatch repair genes,which predispose them to specific types of cancer. Because individuals within LS families can experience multiple cancers over their lifetime, we developed a progressive three-state model to estimate the disease risk from a healthy (state 0) to a first cancer (state 1) and then to a second cancer (state 2). Ascertainment correction of the likelihood was made to adjust for complex sampling designs with carrier probabilities for family members with missing genotype information estimated using their family's observed genotype and phenotype information in a one-step expectation-maximization algorithm. A sandwich variance estimator was employed to overcome possible model misspecification. The main objective of this paper is to estimate the disease risk (penetrance) for age at a second cancer after someone has experienced a first cancer that is also associated with a mutated gene. Simulation study results indicate that our approach generally provides unbiased risk estimates and low root mean squared errors across different family study designs, proportions of missing genotypes, and risk heterogeneities. An application to 12 large LS families from Newfoundland demonstrates that the risk for a second cancer was substantial and that the age at a first colorectal cancer significantly impacted the age at any LS subsequent cancer. This study provides new insights for developing more effective management of mutation carriers in LS families by providing more accurate multiple cancer risk estimates.

  7. 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.

  8. 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.

  9. Family history and risk of pregnancy-associated breast cancer (PABC).

    Science.gov (United States)

    Johansson, Anna L V; Andersson, Therese M-L; Hsieh, Chung-Cheng; Cnattingius, Sven; Dickman, Paul W; Lambe, Mats

    2015-05-01

    The risk of breast cancer is at least two-fold increased in young women with a family history of breast cancer. Pregnancy has a dual effect on breast cancer risk; a short-term increase followed by a long-term protection. We investigated if the risk of breast cancer during and within 10 years following pregnancy is affected by a family history of breast cancer. We followed a cohort of women aged 15-44 years between 1963 and 2009 identified in Swedish population-based registers. Family history was defined as having a mother or sister with breast cancer. We estimated incidence rate ratios of breast cancer during pregnancy and time intervals up to 10 years post-delivery, with a focus on pregnancy-associated breast cancer (PABC), defined as breast cancer during pregnancy or within 2 years post-delivery. In 3,452,506 women, there were 15,548 cases of breast cancer (1208 were PABC). Compared to nulliparous women, the risk of breast cancer was decreased during pregnancy, similar during first year and increased during second year post-delivery. The pattern was similar in women with or without family history of breast cancer. A peak in risk was observed 5-6 years following the first birth regardless of family history. After a second birth, this peak was only present in women with a family history. Our results indicate that women with a family history of breast cancer do not have a different breast cancer risk during and within 10 years following pregnancy compared to women without a family history.

  10. US correlation for MRI-detected breast lesions in women with familial risk of breast cancer.

    NARCIS (Netherlands)

    Sim, L.S.; Hendriks, J.H.C.L.; Bult, P.; Fook-Chong, S.M.

    2005-01-01

    AIM: To examine the value of US correlation for MRI-detected breast lesions in women with familial risk of breast cancer. METHODS: From an initial dataset of 245 women with positive family history who had breast cancer surveillance involving mammography or MRI between November 1994 and February 2001

  11. 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

    Surveillance guidelines for the management of familial colorectal cancer (FCC), a dominant family history of colorectal cancer in which the polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six...

  12. Molecular functions and significance of the MTA family in hormone-independent cancer.

    Science.gov (United States)

    Ning, Zhifeng; Gan, Jinfeng; Chen, Chaoying; Zhang, Dianzheng; Zhang, Hao

    2014-12-01

    The members of the metastasis-associated protein (MTA) family play pivotal roles in both physiological and pathophysiological processes, especially in cancer development and metastasis, and their role as master regulators has come to light. Due to the fact that they were first identified as crucial factors in estrogen receptor-mediated breast cancer metastasis, most of the early studies focused on their hormone-dependent functions. However, the accumulating evidence shows that the members of MTA family are deregulated in most, if not all, the cancers studied so far. Therefore, the levels as well as the activities of the MTA family members are widely accepted as potential biomarkers for diagnosis, prognosis, and predictors of overall survival. They function differently in different cancers with specific mechanisms. p53 and HIF-1α appear to be the respectively common upstream and downstream regulator of the MTA family in both development and metastasis of a wide spectrum of cancers. Here, we review the expression and clinical significance of the MTA family, focusing on hormone-independent cancers. To illustrate the molecular mechanisms, we analyze the MTA family-related signaling pathways in different cancers. Finally, targeting the MTA family directly or the pathways involved in the MTA family indirectly could be invaluable strategies in the development of cancer therapeutics.

  13. Family history of cancer and the risk of laryngeal cancer: a case-control study from Italy and Switzerland.

    Science.gov (United States)

    Garavello, Werner; Turati, Federica; Bosetti, Cristina; Talamini, Renato; Levi, Fabio; Lucenteforte, Ersilia; Chiesa, Fausto; Franceschi, Silvia; La Vecchia, Carlo; Negri, Eva

    2012-02-01

    Only limited data is available on the relationship between family history of laryngeal and other neoplasms and laryngeal cancer risk. We investigated the issue using data from a multicentre case-control study conducted in Italy and Switzerland between 1992 and 2009 including 852 cases with histologically confirmed laryngeal cancer and 1970 controls admitted to hospital for acute, non neoplastic conditions. Unconditional logistic regression models adjusted for age, sex, study center, education, tobacco smoking, alcohol drinking and number of siblings were used to estimate the odds ratios (ORs) of laryngeal cancer. The multivariate OR was 2.8 (95% confidence interval [CI], 1.5-5.3) in subjects reporting a first-degree relative with laryngeal cancer, as compared to subjects with no family history. The OR was higher when the relative was diagnosed before 60 years of age (OR = 3.5, 95% CI 1.4-8.8). As compared to subjects without family history, non-smokers, and moderate drinkers, the OR was 37.1 (95% CI 9.9-139.4) for current smokers, heavy drinkers, with family history of laryngeal cancer. Family history of colorectal (OR = 1.5, 95% CI 1.0-2.3) and kidney (OR = 3.8, 95% CI 1.2-12.1) cancer were also associated to an increased risk of laryngeal cancer, while no significant increase in risk was found for family history of cancer at all sites, excluding the larynx (OR = 1.1).

  14. 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.

  15. "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.

  16. Mutation screening of mismatch repair gene Mlh3 in familial esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Hong-Xu Liu; Yu Li; Xue-Dong Jiang; Hong-Nian Yin; Lin Zhang; Yu Wang; Jun Yang

    2006-01-01

    AIM: To shed light on the possible role of mismatch repair gene Mlh3 in familial esophageal cancer (FEC).METHODS: A total of 66 members from 10 families suggestive of a genetic predisposition to hereditary esophageal cancer were screened for germline mutations in Mlh3 with denaturing high performance liquid chromatography (DHPLC), a newly developed method of comparative sequencing based on heteroduplex detection. For all samples exhibiting abnormal DHPLC profiles,sequence changes were evaluated by cycle sequencing.For any mutation in family members, we conducted a segregation study to compare its prevalence in sporadic esophageal cancer patients and normal controls.RESULTS: Exons of Mlh3 in all samples were successfully examined. Overall, 4 missense mutations and 3 polymorphisms were identified in 4 families. Mlh3 missense mutations in families 9 and 10 might be pathogenic, but had a reduced penetrance. While in families 1 and 7,there was no sufficient evidence supporting the monogenic explanations of esophageal cancers in families.The mutations were found in 33% of high-risk families and 50% of low-risk families.CONCLUSION: Mlh3 is a high risk gene with a reduced penetrance in some families. However, it acts as a low risk gene for esophageal cancer in most families. Mutations of Mlh3 may work together with other genes in an accumulated manner and result in an increased risk of esophageal tumor. DHPLC is a robust and sensitive technique for screening gene mutations.

  17. Enhanced cytotoxicity of optimized liposomal genistein via specific induction of apoptosis in breast, ovarian and prostate carcinomas.

    Science.gov (United States)

    Phan, Vu; Walters, Jarvis; Brownlow, Bill; Elbayoumi, Tamer

    2013-12-01

    Clinical use of genistein against cancer is limited by its extremely low aqueous solubility, poor bioavailability and pharmacokinetics. Based on structural analogy with steroidal compounds, liposomal vehicle compositions were designed and optimized for maximum incorporation of genistein's flavonoid structure. Model conventional and stealth liposomes of genistein (GenLip)--incorporating unsaturated phospholipids and cholesterol--have demonstrated enhanced drug solubilization (over 350-folds > aqueous drug solution), shelf-life stability, and extended release profile. Owing to effective cellular delivery, preservation of genistein's antioxidant activity was confirmed through marked neutralization of peroxides via GenLip, in both quantitative and microscopic fluorescent-probe oxidation assays. Furthermore, significant broad-spectrum anticancer efficacy of GenLip, in murine and human cancer cell lines (p induction level of P53-independent apoptotic pathway markers, compared to all treatments, in our assays (namely, mitochondrial polarization, and caspase-3/7 enzymes). Our proof-of-principle pharmaceutical design of genistein-loaded liposomes shows optimal loading capacity and physico-chemical properties, which improved cellular delivery and specific pro-apototic effectiveness of incorporated drug, against various cancers.

  18. 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

  19. TNM staging and classification (familial and nonfamilial of breast cancer in Jordanian females

    Directory of Open Access Journals (Sweden)

    M F Atoum

    2010-01-01

    Full Text Available Purpose : Staging of breast tumor has important implications for treatment and prognosis. This study aims at pinpointing the frequency of each stage among familial and nonfamilial breast cancers. Materials and Methods : Ninety-nine Jordanian females diagnosed with familial and nonfamilial breast cancer between 2000 and 2002 were enrolled in this study All breast cancer cases were staged according to the TNM classification into in situ, early invasive, advanced invasive and metastatic. Results : Forty-three cases were familial breast cancer and 56 were nonfamilial. One female breast cancer was diagnosed with ductal carcinoma in situ (DCIS cancer. Fifty cases were diagnosed in early stages of invasive breast cancer, of which 31 cases were familial, 29 cases were classified as advanced invasive, where 21 cases were nonfamilial and 19 cases were metastatic stage of breast cancer, with 16 nonfamilial cases. Stage 2b was the most common stage of early invasive cases and represented 48% of the early stage of breast cancer. On the other hand, among cases diagnosed with advanced invasive breast cancer, stage 3a was the most common stage and represented 89.6% of the advanced stage. Interestingly, all cases of stage 3a belonged to TNM stages of T2N2M0 and T3N1M0. The tumor size in all cases of Jordanian females diagnosed with advanced invasive breast cancer exceeded 2 cm in size due to selection bias from symptomatic women in our study. Conclusion : The incidence of nonfamilial breast cancer was slightly higher than that of the familial type amongst studied the Jordanian females studied. The early invasive stage of breast cancer was more common in the familial while the advanced invasive and metastatic breast cancer cases were encountered more often in the nonfamilial type. Our study was based on a small sample and symptomatic women. Therefore, more research with larger population samples is needed to confirm this conclusion.

  20. 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.

  1. A primary care audit of familial risk in patients with a personal history of breast cancer.

    Science.gov (United States)

    Nathan, Paul; Ahluwalia, Aneeta; Chorley, Wendy

    2014-12-01

    Breast cancer is the most common cancer diagnosed in women, both in the UK and worldwide. A small proportion of women are at very high risk of breast cancer, having a particularly strong family history. The National Institute for Health and Clinical Excellence (NICE) has advised that practitioners should not, in most instances, actively seek to identify women with a family history of breast cancer. An audit was undertaken at an urban primary care practice of 15,000 patients, using a paper-based, self-administered questionnaire sent to patients identified with a personal history of breast cancer. The aim of this audit was to determine whether using targeted screening of relatives of patients with breast cancer to identify familial cancer risk is worthwhile in primary care. Since these patients might already expected to have been risk assessed following their initial diagnosis, this audit acts as a quality improvement exercise. The audit used a validated family history questionnaire and risk assessment tool as a screening approach for identifying and grading familial risk in line with the NICE guidelines, to guide referral to the familial cancer screening service. The response rate to family history questionnaires was 54 % and the majority of patients responded positively to their practitioner seeking to identify familial cancer risks in their family. Of the 57 returned questionnaires, over a half (54 %) contained pedigrees with individuals eligible for referral. Patients and their relatives who are often registered with the practice welcome the discussion. An appropriate referral can therefore be made. The findings suggest a role for primary care practitioners in the identification of those at higher familial risk. However integrated systems and processes need designing to facilitate this work.

  2. 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...... patients within the same family. METHODS: In the current study we analyzed a collection of 70 frozen breast tumor biopsies from a total of 58 families by global RNA profiling and promoter methylation analysis. RESULTS: We show that distinct functional subgroupings, similar to the intrinsic molecular breast...

  3. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease

    NARCIS (Netherlands)

    Collaborative Group on Hormona, l Factors; van den Brandt, P.A.; Goldbohm, R.A.

    2001-01-01

    Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Collaborative Group on Hormonal Factors in Breast Cancer. BACKGROUND: Women with a family history of breast cancer are

  4. 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.

  5. A model for patient-direct screening and referral for familial cancer risk.

    Science.gov (United States)

    Niendorf, Kristin B; Geller, Melissa A; Vogel, Rachel Isaksson; Church, Timothy R; Leininger, Anna; Bakke, Angela; Madoff, Robert D

    2016-10-01

    Patients at increased familial risk of cancer are sub-optimally identified and referred for genetic counseling. We describe a systematic model for information collection, screening and referral for hereditary cancer risk. Individuals from three different clinical and research populations were screened for hereditary cancer risk using a two-tier process: a 7-item screener followed by review of family history by a genetic counselor and application of published criteria. A total of 869 subjects participated in the study; 769 in this high risk population had increased familial cancer risk based on the screening questionnaire. Of these eligible participants, 500 (65.0 %) provided family histories and 332 (66.4 %) of these were found to be at high risk of a hereditary cancer syndrome, 102 (20.4 %) at moderate familial cancer risk, and 66 (13.2 %) at average risk. Three months following receipt of the risk result letter, nearly all respondents found the process at least somewhat helpful (98.4 %). All participants identified as high-risk were mailed a letter recommending genetic counseling and were provided appointment tools. After 1 year, only 13 (7.3 %) of 179 high risk respondents reported pursuit of recommended genetic counseling. Participants were willing to provide family history information for the purposes of risk assessment; however, few patients pursued recommended genetic services. This suggests that cancer family history registries are feasible and viable but that further research is needed to increase the uptake of genetic counseling.

  6. 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].

  7. 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.

  8. Family caregivers of cancer patients: perceived burden and symptoms during the early phases of cancer treatment.

    Science.gov (United States)

    Stenberg, Una; Cvancarova, Milada; Ekstedt, Mirjam; Olsson, Mariann; Ruland, Cornelia

    2014-01-01

    This study investigated levels of symptoms, caregiver burden, and changes over time in 278 family caregivers (FC) of cancer patients. FCs experienced high levels of depressive symptoms and sleep disturbance, low levels of fatigue, and low to moderate levels of caregiver burden, yet these symptoms remained relatively stable over time. Being female and not being employed were factors associated with an increased risk of symptoms and caregiver burden. The understanding evolving from this study can enhance social- and health care professionals' awareness of FCs' challenging situation and the potential impact this has on the FCs' ability to provide care to the patient.

  9. Familial breast cancer: what the radiologist needs to know; Familiaere Brustkrebserkrankung: klinische Grundlagen und Frueherkennung

    Energy Technology Data Exchange (ETDEWEB)

    Kuhl, C.K. [Radiologische Klinik, Universitaetskliniken Bonn (Germany)

    2006-07-15

    About 10% of breast cancers are ''hereditary'', i.e. caused by a pathogenic mutation in one of the ''breast and ovarian cancer susceptibility genes'' (BRCA). The BRCA genes 1 and 2 identified to date follow an autosomal dominant inheritance pattern. A clustering of breast cancer in a family without a documented mutation and without a recognizable inheritance pattern is usually referred to as ''familial cancer''. A distinction between hereditary and familial is difficult in the individual case because not all of the genetic mutations that cause breast cancer susceptibility are known and thus amenable to genetic testing. Women who are suspected of or documented as carrying a breast cancer susceptibility gene face a substantially increased lifetime risk of breast (and ovarian) cancer ranging from 60-80% for breast and up to 40% for ovarian cancer. In addition, the disease develops at a young age (the personal risk starts increasing at age 25; average age of diagnosis is 40). BRCA-associated breast cancers tend to exhibit histologic and histochemical evidence of aggressive biologic behavior (usually grade 3, receptor negative) with very fast growth rates. In particular BRCA1-associated breast cancer may be indistinguishable from fibroadenomas: They appear as well-defined, roundish, hypoechoic masses with smooth borders, without posterior acoustic shadowing on ultrasound, without associated microcalcifications on mammography, and with strong wash-out phenomenon on breast MRI. This article reviews the different options that exist for the prevention of familial or hereditary breast cancer and the specific difficulties that are associated with the radiological diagnosis of these cancers. Lastly, an overview is given of the current evidence regarding the effectiveness of the different imaging modalities for early diagnosis of familial and hereditary breast cancer. (orig.)

  10. Cancer anorexia-cachexia syndrome: psychological effect on the patient and family.

    Science.gov (United States)

    McClement, Susan

    2005-01-01

    The majority of patients with advanced cancer experience weight loss, reduced appetite, fatigue, and weakness. Chronic nausea and early satiety may also occur. This constellation of symptoms is known as the cancer anorexia-cachexia syndrome. Together with cancer pain, cancer anorexia-cachexia syndrome has been identified as 1 of the 2 most frequent and devastating problems affecting individuals with advanced malignancies. Research examining the issue of cancer anorexia-cachexia syndrome has been conducted; however, such work is largely biomedical in orientation. In contrast, the psychologic dimensions of the cancer anorexia-cachexia syndrome experience from the perspective of terminally ill patients and their family members is less well explored or described. The ability to provide psychosocial support to patients and families requires that caregivers appreciate the psychologic effect of cancer anorexia and cachexia on these individuals. This article examines that effect in light of existing knowledge and discusses the clinical implications arising from this work.

  11. Family Life

    Science.gov (United States)

    ... With Family and Friends > Family Life Request Permissions Family Life Approved by the Cancer.Net Editorial Board , ... your outlook on the future. Friends and adult family members The effects of cancer on your relationships ...

  12. Tissue microarrays for testing basal biomarkers in familial breast cancer cases

    Directory of Open Access Journals (Sweden)

    Rozany Mucha Dufloth

    Full Text Available CONTEXT AND OBJECTIVE: The proteins p63, p-cadherin and CK5 are consistently expressed by the basal and myoepithelial cells of the breast, although their expression in sporadic and familial breast cancer cases has yet to be fully defined. The aim here was to study the basal immunopro-file of a breast cancer case series using tissue microarray technology. DESIGN AND SETTING: This was a cross-sectional study at Universidade Estadual de Campinas, Brazil, and the Institute of Pathology and Mo-lecular Immunology, Porto, Portugal. METHODS: Immunohistochemistry using the antibodies p63, CK5 and p-cadherin, and also estrogen receptor (ER and Human Epidermal Receptor Growth Factor 2 (HER2, was per-formed on 168 samples from a breast cancer case series. The criteria for identifying women at high risk were based on those of the Breast Cancer Linkage Consortium. RESULTS: Familial tumors were more frequently positive for the p-cadherin (p = 0.0004, p63 (p < 0.0001 and CK5 (p < 0.0001 than was sporadic cancer. Moreover, familial tumors had coexpression of the basal biomarkers CK5+/ p63+, grouped two by two (OR = 34.34, while absence of coexpression (OR = 0.13 was associ-ated with the sporadic cancer phenotype. CONCLUSION: Familial breast cancer was found to be associated with basal biomarkers, using tissue microarray technology. Therefore, characterization of the familial breast cancer phenotype will improve the understanding of breast carcinogenesis.

  13. Caring for families with a family history of cancer: why concerns about genetic predisposition are missing from the palliative agenda.

    Science.gov (United States)

    Lillie, Alison Kate; Clifford, Collette; Metcalfe, Alison

    2011-03-01

    Care of the family is integral to palliative care, but little attention has been paid to the way nurses, or other healthcare professionals, are responding to the needs of families who are concerned about whether their family history of cancer is associated with an inherited genetic predisposition. This paper discusses how palliative care nurses perceive the care needs of patients with a family history of cancer. Data were collected through recorded, semi-structured interviews with 10 nurses who had worked in specialist palliative care. The findings show that there are cogent arguments and concerns about raising the issue of an inherited genetic predisposition at the end of life (especially when the patient is close to death and there is a lack of knowledge about genetics). Nevertheless, exemplar cases are used to illustrate the reasons why it is important that nurses working in specialist palliative care settings are aware of the needs of this patient group. The paper highlights that nurses not only need an appropriate knowledge base but also an insight of what can be achieved when supporting patients with a family history of cancer.

  14. 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.

  15. 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.

  16. Correlation between low neuraminidase blood levels and a predisposition toward family-related breast cancer.

    Science.gov (United States)

    Rothenberg, R E; Laraja, R D; Imran-Ul-Hag; Saber, A A; Nadkarni, M

    1996-11-01

    It has been shown that high sialic acid levels are often found in conjunction with breast cancer, and these high concentrations are thought to be due to deficiency of the enzyme neuraminidase. The study proposes to elicit a relationship between low levels of blood neuraminidase and a family history of breast cancer. Neuraminidase blood levels were measured in 30 healthy women between the ages of 35 and 65 years with no evidence of a family history of breast cancer (control group), and in 33 healthy women between the ages of 35 to 65 years, all of whom had immediate members of their families with breast cancer (study group). The mean level of the blood neuraminidase was found to be 1.375 units in the control group. On the other hand, the mean level for the study group was 1.256 units. The difference between the two groups is statistically significant, (P value breast cancer.

  17. A meta-analytic review of the influence of pediatric cancer on parent and family functioning.

    Science.gov (United States)

    Pai, Ahna L H; Greenley, Rachel Neff; Lewandowski, Amy; Drotar, Dennis; Youngstrom, Eric; Peterson, Catherine Cant

    2007-09-01

    This study used meta-analytic methods to compare the functioning of parents of children with cancer to parents of physically healthy children or normative samples. A meta-analysis using fixed effects, weighted least squares methods was conducted on 29 studies examining psychological distress and marital and family functioning among parents of children with cancer. Mothers and fathers of children newly diagnosed with cancer reported significantly greater distress than comparison samples. Mothers reported greater distress than fathers up to 12 months postdiagnosis. Mothers of children with cancer reported higher levels of family conflict than mothers of healthy children. Findings suggest that pediatric cancer impacts parents' perceptions of self- and family functioning, especially within the 1st year following diagnosis.

  18. Interaction of Werner and Bloom syndrome genes with p53 in familial breast cancer.

    Science.gov (United States)

    Wirtenberger, Michael; Frank, Bernd; Hemminki, Kari; Klaes, Rüdiger; Schmutzler, Rita K; Wappenschmidt, Barbara; Meindl, Alfons; Kiechle, Marion; Arnold, Norbert; Weber, Bernhard H F; Niederacher, Dieter; Bartram, Claus R; Burwinkel, Barbara

    2006-08-01

    Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature ageing and cancer predisposition. We tested the hypothesis whether three polymorphic, non-conservative amino acid exchanges in WRN and BLM act as low-penetrance familial breast cancer risk factors. Moreover, we examined the putative impact of p53 MspI 1798G>A, which is completely linked to p53PIN3, a 16 bp insertion/duplication that has been associated with reduced p53 expression, on familial breast cancer risk. Genotyping analyses, performed on 816 BRCA1/2 mutation-negative German familial breast cancer patients and 1012 German controls, revealed a significant association of the WRN Cys1367Arg polymorphism with familial breast cancer (OR = 1.28, 95% CI 1.06-1.54) and high-risk familial breast cancer (OR = 1.32, 95% CI 1.06-1.65). The analysis of p53 MspI 1798G>A, which is completely linked to p53PIN3, showed a significantly increased familial breast cancer risk for carriers of the 16 bp insertion/duplication, following a recessive mode (OR = 2.15, 95% CI = 1.12-4.11). WRN Cys1367Arg, located in the C-terminus, the binding site of p53, is predicted to be damaging. The joint effect of WRN Cys1367Arg and p53 MspI resulted in an increased breast cancer risk compared to the single polymorphisms (OR = 3.39, 95% CI 1.19-9.71). In conclusion, our study indicates the importance of inherited variants in the WRN and p53 genes for familial breast cancer susceptibility.

  19. Familial aggregation of childhood and adult cancer in the Utah genealogy.

    Science.gov (United States)

    Neale, Rachel E; Stiller, Charles A; Bunch, Kathryn J; Milne, Elizabeth; Mineau, Geraldine P; Murphy, Michael F G

    2013-12-15

    A small proportion of childhood cancer is attributable to known hereditary syndromes, but whether there is any familial component to the remainder remains uncertain. We explored familial aggregation of cancer in a population-based case-control study using genealogical record linkage and designed to overcome limitations of previous studies. Subjects were selected from the Utah Population Database. We compared risk of cancer in adult first-degree relatives of children who were diagnosed with cancer with the risk in relatives of children who had not had a cancer diagnosed. We identified 1,894 childhood cancer cases and 3,788 controls; 7,467 relatives of cases and 14,498 relatives of controls were included in the analysis. Relatives of children with cancer had a higher risk of cancer in adulthood than relatives of children without cancer [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.11-1.56]; this was restricted to mothers and siblings and was not evident in fathers. Familial aggregation appeared stronger among relatives of cases diagnosed before 5 years of age (OR 1.48, 95% CI 1.13-1.95) than among relatives of cases who were older when diagnosed (OR 1.22, 95% CI 0.98-1.51). These findings provide evidence of a generalized excess of cancer in the mothers and siblings of children with cancer. The tendency for risk to be higher in the relatives of children who were younger at cancer diagnosis should be investigated in other large data sets. The excesses of thyroid cancer in parents of children with cancer and of any cancer in relatives of children with leukemia merit further investigation.

  20. Cystic disease, family history of breast cancer, and use of oral contraceptives.

    Science.gov (United States)

    Vakil, D V; Elinson, L; Morgan, R W

    1981-01-01

    Epidemiologic studies show a lower frequency of fibrocystic breast disease among users of oral contraceptives than among women who have never used them. Family history of breast cancer appears to be more common among benign breast disease patients than among their controls. To determine the use of oral contraceptives and the presence of family history of breast cancer, information was obtained from 211 cystic cases and their matched controls from the metropolitan Toronto area. Cystic cases compared to controls had a higher proportion of women with a family history of breast cancer (21% vs 15%). For both a positive and negative family history of breast cancer, as well as for all women combined, the mean duration of oral contraceptive use was lower for cystic cases than for controls. The odds ratio for oral contraceptive use according to family history of breast cancer for cystic cases and controls was 0.42 and 0.81 respectively. The possibility that a woman is more protected against benign breast disease by using oral contraceptives if she has a family history of breast cancer deserves more attention in future investigations on the long-term effects of birth control pills.

  1. 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.

  2. Striving to survive: families' lived experiences when a child is diagnosed with cancer.

    Science.gov (United States)

    Björk, Maria; Wiebe, Thomas; Hallström, Inger

    2005-01-01

    When a child is ill with cancer, this affects the whole family for long periods. The aim of this study was to elucidate the family's lived experience when a child in the family was diagnosed with cancer. A descriptive inductive design with a hermeneutic phenomenological approach including interviews with 17 families (parents, children, and siblings) was chosen. The families' lived experience was described as a 2-fold essential theme comprising "a broken life world" and an immediate "striving to survive." The families' secure everyday life disappeared and was replaced by fear, chaos, and loneliness. When striving to make the child and the family survive, family members strove to feel hope and have a positive focus, to gain control, and to feel close to other people. Phenomenological human science research can deepen the understanding of the meaning of being a family with a child who is ill with cancer and can help pediatric oncology staff become increasingly thoughtful, and thus better prepared to take action to diminish the chaos occurring in the family.

  3. Clinical findings with implications for genetic testing in families with clustering of colorectal cancer

    NARCIS (Netherlands)

    Wijnen, JT; Vasen, HFA; Khan, PM; Zwinderman, AH; van der Klift, H; Mulder, A; Tops, C; Moller, P; Fodde, R; Menko, F; Taal, B; Nagengast, F; Brunner, H; Kleibeuker, J; Sijmons, R; Griffioen, G; Brocker-Vriends, A; Bakker, E; van Leeuwen-Cornelisse, [No Value; Meijers-Heijboer, A; Lindhout, D; Breuning, M; Post, J; Schaap, C; Apold, J; Heimdal, K; Bertario, L; Bisgaard, ML; Goetz, P

    1998-01-01

    Background Germ-line mutations in DNA mismatch-repair genes (MSH2, MLH1, PIMS1, PMS2, and MSH6) cause susceptibility to hereditary nonpolyposis colorectal cancer. We assessed the prevalence of MSH2 and MLH1 mutations in families suspected of having hereditary nonpolyposis colorectal cancer and evalu

  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. 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

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

    NARCIS (Netherlands)

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

  8. 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, Annemieke; 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

  9. 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…

  10. Early detection of breast and ovarian cancer in families with BRCA mutations

    NARCIS (Netherlands)

    Vasen, HFA; Tesfay, E; Mourits, MJE; Rutgers, E; Verheyen, R; Oosterwijk, J; Beex, L; Boonstra, J.

    2005-01-01

    Women at risk of breast and ovarian cancer due to a genetic predisposition may opt for preventive surgery or surveillance. The aim of this study was to determine the effectiveness of surveillance in families with a BRCA mutation. Sixty-eight BRCA-families underwent surveillance using annual mammogra

  11. 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.

  12. Psychological impact of the diagnosis of breast cancer on the patient and her family.

    Science.gov (United States)

    Northouse, L L

    1992-01-01

    The diagnosis of breast cancer creates emotional distress for patients as well as family members. This article reviews studies on the psychological adjustment of women and their family members during the diagnosis, hospitalization, and early convalescence from breast surgery. Studies indicate that the diagnostic phase is an extremely stressful time for women, marked by high anxiety, uncertainty, and difficulty making decisions. The hospital phase is especially difficult for spouses, who must juggle work responsibilities with added home responsibilities and also spend time at the hospital supporting their wives. In the convalescent phase, patients and family members need to adjust to changes in family roles, cope with fears about recurrence, and learn to balance the needs of all family members. In order to provide high quality health care to breast cancer patients and their family members, physicians and nurses need to address the emotional as well as the physical aspects of recovery.

  13. 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.

  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. Lessons learned in developing a culturally adapted intervention for African-American families coping with parental cancer.

    Science.gov (United States)

    Davey, Maureen P; Kissil, Karni; Lynch, Laura; Harmon, La-Rhonda; Hodgson, Nancy

    2012-12-01

    Prior clinical research supports the effectiveness of cancer support groups for cancer patients and their families, yet African-American families continue to be underrepresented in cancer support groups and in cancer clinical research studies. In order to fill this gap, we developed and evaluated a culturally adapted family support group for African-American families coping with parental cancer. We encountered unexpected challenges in overcoming barriers to recruitment, partnering with oncology providers, and building trust with the African-American community and African-American families coping with parental cancer. We describe actions taken during the two phases of this study and lessons learned along the way about recruiting and engaging African-American families in cancer support group studies, partnering with oncology providers, networking with the African-American community, and the importance of demonstrating cultural sensitivity to overcome the understandable historical legacy of mistrust.

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

    Science.gov (United States)

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

    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 ionizing radiation. Moreover, a recurrent germline mutation was reported in Finnish high-risk breast cancer families. To determine if ABRAXAS could be a breast cancer susceptibility gene in other populations, we conducted a population-based case-control mutation screening study of the coding exons and exon/intron boundaries of ABRAXAS in the Breast Cancer Family Registry. In addition to the common variant p.Asp373Asn, sixteen distinct rare variants were identified. Although no significant difference in allele frequencies between cases and controls was observed for the identified variants, two variants, p.Gly39Val and p.Thr141Ile, were shown to diminish phosphorylation of gamma-H2AX in MCF7 human breast adenocarcinoma cells, an important biomarker of DNA double-strand breaks. Overall, likely damaging or neutral variants were evenly represented among cases and controls suggesting that rare variants in ABRAXAS may explain only a small proportion of hereditary breast cancer. PMID:27270457

  17. 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

  18. Nationwide registry-based analysis of cancer clustering detects strong familial occurrence of Kaposi sarcoma.

    Science.gov (United States)

    Kaasinen, Eevi; Aavikko, Mervi; Vahteristo, Pia; Patama, Toni; Li, Yilong; Saarinen, Silva; Kilpivaara, Outi; Pitkänen, Esa; Knekt, Paul; Laaksonen, Maarit; Artama, Miia; Lehtonen, Rainer; Aaltonen, Lauri A; Pukkala, Eero

    2013-01-01

    Many cancer predisposition syndromes are rare or have incomplete penetrance, and traditional epidemiological tools are not well suited for their detection. Here we have used an approach that employs the entire population based data in the Finnish Cancer Registry (FCR) for analyzing familial aggregation of all types of cancer, in order to find evidence for previously unrecognized cancer susceptibility conditions. We performed a systematic clustering of 878,593 patients in FCR based on family name at birth, municipality of birth, and tumor type, diagnosed between years 1952 and 2011. We also estimated the familial occurrence of the tumor types using cluster score that reflects the proportion of patients belonging to the most significant clusters compared to all patients in Finland. The clustering effort identified 25,910 birth name-municipality based clusters representing 183 different tumor types characterized by topography and morphology. We produced information about familial occurrence of hundreds of tumor types, and many of the tumor types with high cluster score represented known cancer syndromes. Unexpectedly, Kaposi sarcoma (KS) also produced a very high score (cluster score 1.91, p-value <0.0001). We verified from population records that many of the KS patients forming the clusters were indeed close relatives, and identified one family with five affected individuals in two generations and several families with two first degree relatives. Our approach is unique in enabling systematic examination of a national epidemiological database to derive evidence of aberrant familial aggregation of all tumor types, both common and rare. It allowed effortless identification of families displaying features of both known as well as potentially novel cancer predisposition conditions, including striking familial aggregation of KS. Further work with high-throughput methods should elucidate the molecular basis of the potentially novel predisposition conditions found in this

  19. Nationwide registry-based analysis of cancer clustering detects strong familial occurrence of Kaposi sarcoma.

    Directory of Open Access Journals (Sweden)

    Eevi Kaasinen

    Full Text Available Many cancer predisposition syndromes are rare or have incomplete penetrance, and traditional epidemiological tools are not well suited for their detection. Here we have used an approach that employs the entire population based data in the Finnish Cancer Registry (FCR for analyzing familial aggregation of all types of cancer, in order to find evidence for previously unrecognized cancer susceptibility conditions. We performed a systematic clustering of 878,593 patients in FCR based on family name at birth, municipality of birth, and tumor type, diagnosed between years 1952 and 2011. We also estimated the familial occurrence of the tumor types using cluster score that reflects the proportion of patients belonging to the most significant clusters compared to all patients in Finland. The clustering effort identified 25,910 birth name-municipality based clusters representing 183 different tumor types characterized by topography and morphology. We produced information about familial occurrence of hundreds of tumor types, and many of the tumor types with high cluster score represented known cancer syndromes. Unexpectedly, Kaposi sarcoma (KS also produced a very high score (cluster score 1.91, p-value <0.0001. We verified from population records that many of the KS patients forming the clusters were indeed close relatives, and identified one family with five affected individuals in two generations and several families with two first degree relatives. Our approach is unique in enabling systematic examination of a national epidemiological database to derive evidence of aberrant familial aggregation of all tumor types, both common and rare. It allowed effortless identification of families displaying features of both known as well as potentially novel cancer predisposition conditions, including striking familial aggregation of KS. Further work with high-throughput methods should elucidate the molecular basis of the potentially novel predisposition conditions

  20. 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.

  1. 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....

  2. 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.

  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. A DVD program on fall prevention skills training for cancer family caregivers.

    Science.gov (United States)

    Potter, Patricia; Olsen, Sarah; Kuhrik, Marilee; Kuhrik, Nancy; Huntley, Lance R

    2012-03-01

    This feasibility study tested an instructional DVD program for improving cancer family caregivers' knowledge and preparedness in fall prevention and reducing fall occurrence among the patients they care for at home. DVD program features included training caregivers on safe mobility skills. Family caregivers of cancer patients were surveyed before and after viewing the DVD program on "Moving Safely" in the home. Cancer patients were followed 4 months postintervention to determine if fall occurrence was reduced. There was a decrease in the number of patients who fell postintervention compared with those who fell preintervention. Caregivers' perceptions of knowledge about fall prevention improved significantly after viewing the DVD. An instructional DVD program is an effective educational tool for preparing family caregivers with the knowledge and skills needed to reduce the incidence of falls in the home setting. Educators must develop programs for preparing family caregivers to perform nursing skills within the home.

  5. 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

  6. 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

  7. [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

  8. Cancer and the family: strategies to assist spouses.

    Science.gov (United States)

    Northouse, L L; Peters-Golden, H

    1993-05-01

    Research that has been conducted with spouses of cancer patients documents the nature of their stress, the duration of their stress, and the concerns that they confront over the course of the illness. A variety of intervention strategies have been used to assist spouses in dealing with the stressful effects of cancer. Two major categories of intervention strategies are providing information and offering support.

  9. 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

  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. A family-based model to predict fear of recurrence for cancer survivors and their caregivers.

    Science.gov (United States)

    Mellon, Suzanne; Kershaw, Trace S; Northouse, Laurel L; Freeman-Gibb, Laurie

    2007-03-01

    Although fear of cancer recurrence is a great concern among survivors and their families, few studies have examined predictors of fear of recurrence. The purpose of this study was to identify factors associated with fear of recurrence in a population-based sample (N = 246) and determine if survivors and family caregivers influenced one another's fear of recurrence. A family framework guided the study and analyses included multilevel modeling using the Actor-Partner Interdependence Model. Results indicated that survivors and family caregivers influenced each other's fear of recurrence and that caregivers had significantly more fear of recurrence than survivors. More family stressors, less positive meaning of the illness, and age were related to elevated fear of cancer recurrence for both survivors and caregivers.

  12. Truth disclosure of cancer diagnoses and its influence on bereaved Japanese families.

    Science.gov (United States)

    Mizuno, Michiyo; Onishi, Chiemi; Ouishi, Fumiko

    2002-10-01

    The purpose of this study was to investigate how patients with cancer and their families are informed of the results of the patients' diagnoses. The bereaved families' assessments and satisfaction with the consequences of their decisions were examined after the patients' deaths. Data were collected from the bereaved families of 53 patients who had died of lung cancer at a Japanese university hospital between January 1994 and December 1997. Data were analyzed by employing descriptive statistics for each factor. Fifty-three bereaved families responded to the questionnaire. The true diagnosis-lung cancer-was disclosed to 15.1% of the patients, whereas 26.4% were told that they were suffering from lung tumors. Other less ominous clinical descriptions were given to 58.5% of the participants. Concerning the bereaved families' responses to the manner in which the decisions had been made on truth disclosure, the average degree of satisfaction was expressed as 3.7 cm on a 5.0-cm scale. An ambiguous expression such as "lung tumor" has been arbitrarily interpreted. However, simple truth disclosure to the patient does not necessarily satisfy a bereaved family. If family members can allay a patient's doubt about the diagnosis, the family's satisfaction may improve.

  13. The relationship between socio-demographic characteristics, family environment, and caregiver coping in families of children with cancer.

    Science.gov (United States)

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

    2013-12-01

    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 income or education. Caregiver educational attainment was positively associated with use of planning and active coping styles, while income was not associated with caregiver coping style. Mothers were more likely than fathers to use active coping, instrumental support, religious coping, and emotional support. Men with lower education engaged in greater substance use coping and lower planning. The findings show that educational attainment and caregiver gender influence caregiver coping styles following a pediatric cancer diagnosis and suggest that educational attainment rather than financial resources drive the association between SES and coping. Programs that address educational gaps and teach caregivers planning and active coping skills may be beneficial for parents with lower educational attainment, particularly men.

  14. Breast cancer risk prediction using a polygenic risk score in the familial setting: a prospective study from the Breast Cancer Family Registry and kConFab

    Science.gov (United States)

    Li, Hongyan; Feng, Bingjian; Miron, Alexander; Chen, Xiaoqing; Beesley, Jonathan; Bimeh, Emmanuella; Barrowdale, Daniel; John, Esther M.; Daly, Mary B.; Andrulis, Irene L.; Buys, Saundra S.; Kraft, Peter; Thorne, Heather; Chenevix-Trench, Georgia; Southey, Melissa; Antoniou, Antonis C.; James, Paul A.; Terry, Mary Beth; Phillips, Kelly-Anne; Hopper, John L.; Mitchell, Gillian; Goldgar, David E.

    2016-01-01

    Purpose This study examined the utility of sets of Single Nucleotide Polymorphisms (SNPs) in familial but non-BRCA-associated breast cancer (BC). Methods We derived a polygenic risk score (PRS) based on 24 known BC risk SNPs for 4,365 women from the BCFR and kConFab familial BC cohorts. We compared scores in women based on cancer status at baseline. 2,599 women unaffected at enrollment were followed for an average of 7.4 years. Cox proportional hazards regression was used to analyze the association of PRS with BC risk. The BOADICEA risk prediction algorithm was used to measure risk based on family history alone. Results The mean (SD) PRS baseline was 2.25 (0.35) for the affected and 2.17 (0.35) for unaffected women from combined cohorts (p<10−6). During follow-up, 205 BCs occurred. The hazard ratios for continuous PRS (per SD), and upper vs. lower quintiles were 1.38 (95% CI: 1.22–1.56) and 3.18 (95% CI: 1.84–5.23) respectively. Based on their PRS-based predicted risk, management for up to 23% of women could be altered. Conclusion Including BC-associated SNPs in risk assessment can provide more accurate risk prediction than family history alone and can influence recommendations for cancer screening and prevention modalities for high-risk women. PMID:27171545

  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. 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

  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. Maternal and paternal lineage double heterozygosity alteration in familial breast cancer: a first case report.

    Science.gov (United States)

    Pilato, Brunella; De Summa, Simona; Danza, Katia; Lambo, Rossana; Paradiso, Angelo; Tommasi, Stefania

    2010-12-01

    Hereditary breast cancer syndrome was firstly associated with BRCA1 and BRCA2 genes the mutations of which confer high risk to develop breast and/or ovarian cancer. Double heterozygosity is a rare condition in which both BRCA1 and BRCA2 mutations are present in a family at the same time. In the current study, a family with double heterozygosity has been reported. Furthermore, for the first time a molecular analysis in both proband lineages, maternal and paternal, has been reported to understand the provenience of both germinal mutations.The case regards a woman who developed breast and ovarian cancer with liver metastasis which presented two mutations, each in the two genes, transmitted from her mother and her father, respectively. In this family all available members have been investigated. The concomitant presence of these peculiar mutations was never reported before suggesting a link with Caucasian population from Southern Italy.

  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. 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....

  3. Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer.

    Science.gov (United States)

    Robinson, Dan R; Kalyana-Sundaram, Shanker; Wu, Yi-Mi; Shankar, Sunita; Cao, Xuhong; Ateeq, Bushra; Asangani, Irfan A; Iyer, Matthew; Maher, Christopher A; Grasso, Catherine S; Lonigro, Robert J; Quist, Michael; Siddiqui, Javed; Mehra, Rohit; Jing, Xiaojun; Giordano, Thomas J; Sabel, Michael S; Kleer, Celina G; Palanisamy, Nallasivam; Natrajan, Rachael; Lambros, Maryou B; Reis-Filho, Jorge S; Kumar-Sinha, Chandan; Chinnaiyan, Arul M

    2011-11-20

    Breast cancer is a heterogeneous disease that has a wide range of molecular aberrations and clinical outcomes. Here we used paired-end transcriptome sequencing to explore the landscape of gene fusions in a panel of breast cancer cell lines and tissues. We observed that individual breast cancers have a variety of expressed gene fusions. We identified two classes of recurrent gene rearrangements involving genes encoding microtubule-associated serine-threonine kinase (MAST) and members of the Notch family. Both MAST and Notch-family gene fusions have substantial phenotypic effects in breast epithelial cells. Breast cancer cell lines harboring Notch gene rearrangements are uniquely sensitive to inhibition of Notch signaling, and overexpression of MAST1 or MAST2 gene fusions has a proliferative effect both in vitro and in vivo. These findings show that recurrent gene rearrangements have key roles in subsets of carcinomas and suggest that transcriptome sequencing could identify individuals with rare, targetable gene fusions.

  4. Participation of the family in hospital-based palliative cancer care: perspective of nurses

    Directory of Open Access Journals (Sweden)

    Marcelle Miranda da Silva

    Full Text Available 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.

  5. 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.

  6. 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.

  7. 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.

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

    OpenAIRE

    Gazendam-Donofrio, S.M.; Hoekstra, H. J.; van der Graaf, W. T. A.; van de Wiel, H. B.; Visser, Annemieke; 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, adolescents filled in the Impact of Event Scale and Youth Self-report and parents reported on the adolescents' functioning using the Child Behavior Checklist. Results: Patients and spouses report...

  9. Being cared by a family member: the existential feelings of cancer patients

    OpenAIRE

    Julia Wakiuchi; Anna Maria de Oliveira Salimena; Catarina Aparecida Sales

    2015-01-01

    The present article aimed to understand the daily life of cancer patients under palliative care while experiencing home care provided by family members. This was a Heideggerian phenomenological study with 20 patients being treated at the primary health care service of Northeast Paraná, Brazil, between November 2012 and February 2013. Data collection was based on the following research guiding question: What has been your experience of being cared for by your family? Phenomenological analysis ...

  10. Gene expression in response to ionizing radiation and family history of gastric cancer.

    Science.gov (United States)

    Marcon, Francesca; Silvestrini, Francesco; Siniscalchi, Ester; Palli, Domenico; Saieva, Calogero; Crebelli, Riccardo

    2011-03-01

    Genes and molecular pathways involved in familial clustering of gastric cancer have not yet been identified. The purpose of the present study was to investigate gene expression changes in response to a cellular stress, and its link with a positive family history for this neoplasia. To this aim leukocytes of healthy first-degree relatives of gastric cancer patients and controls were challenged in vitro with ionizing radiation and gene expression evaluated 4 h later on microarrays with 1,800 cancer-related genes. Eight genes, mainly involved in signal transduction and cell cycle regulation, were differentially expressed in healthy relatives of gastric cancer cases. Functional class scoring by Gene Ontology classification highlighted two G-protein related pathways, implicated in the proliferation of neoplastic tissue, which were differentially expressed in healthy subjects with positive family history of gastric cancer. The relative expression of 84 genes related to these pathways was examined using the SYBR green-based quantitative real-time PCR. The results confirmed the indication of an involvement of G-protein coupled receptor pathways in GC familiarity provided by microarray analysis. This study indicates a possible association between familiarity for gastric cancer and altered transcriptional response to ionizing radiation.

  11. Breast and Ovarian Cancer and Family History Risk Categories

    Science.gov (United States)

    ... I J K L M N O P Q R S T U V W X Y Z # Start of Search Controls Search Form Controls Search The CDC Cancel Submit Search The CDC Hereditary Breast and Ovarian Cancer Note: Javascript is disabled or ...

  12. Mutations and polymorphic BRCA variants transmission in breast cancer familial members.

    Science.gov (United States)

    Pilato, Brunella; Martinucci, Marianna; Danza, Katia; Pinto, Rosamaria; Petriella, Daniela; Lacalamita, Rosanna; Bruno, Michele; Lambo, Rossana; D'Amico, Cosimo; Paradiso, Angelo; Tommasi, Stefania

    2011-02-01

    We previously showed that about 80% of breast cancer patients at high risk to carry mutation in BRCA genes presented at least one polymorphism in these genes which resulted potentially harmful by in silico analysis. In the present paper, the genealogic transmission of those polymorphic coding and noncoding variants of BRCA genes in family's members has been investigated. Thirty families, enrolled within the Genetic Counselling Program of our Institute, with probands and at least one-first degree relative (n = 67 family members) available, have been studied for both BRCA1 and BRCA2 pathological mutation and polymorphic variants' transmission. Ten and 6 probands carried Mendelian transmitted mutations in BRCA1 and BRCA2, respectively. Polymorphic coding and noncoding variants were transmitted in each family's relatives with a frequency ranging from 42 to 100%, with similar rate for each SNP in mutated and nonmutated families with the only exception of BRCA1 K1183R significantly more frequent in mutated families (P = 0.004); conversely, this SNP and BRCA2 N372H, were more frequently present in breast cancer relatives belonging to families in which pathological BRCA mutations were not present. Furthermore, specific haplotypes were transmitted in all relatives as BRCA1 871Leu-1038Gly, present in both BRCA mutated and nonmutated families, while BRCA2 289His-991Asp-IVS14+53 C>T present only in BRCAX families suggesting the harmful role of these SNPs. In conclusion, analysis of SNPs maps and modality of their transmission could identify further susceptibility markers and provide a basis for a better DNA-based cancer classification.

  13. 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...

  14. TGFbeta and miRNA regulation in familial and sporadic breast cancer.

    Science.gov (United States)

    Danza, Katia; De Summa, Simona; Pinto, Rosamaria; Pilato, Brunella; Palumbo, Orazio; Carella, Massimo; Popescu, Ondina; Digennaro, Maria; Lacalamita, Rosanna; Tommasi, Stefania

    2017-01-30

    The term 'BRCAness' was introduced to identify sporadic malignant tumors sharing characteristics similar to those germline BRCA-related. Among all mechanisms attributable to BRCA1 expression silencing, a major role has been assigned to microRNAs. MicroRNAs role in familial and sporadic breast cancer has been explored but few data are available about microRNAs involvement in homologous recombination repair control in these breast cancer subgroups. Our aim was to seek microRNAs associated to pathways underlying DNA repair dysfunction in breast cancer according to a family history of the disease. Affymetrix GeneChip microRNA Arrays were used to perform microRNA expression analysis in familial and sporadic breast cancer. Pathway enrichment analysis and microRNA target prediction was carried out using DIANA miRPath v.3 web-based computational tool and miRWalk v.2 database. We analyzed an external gene expression dataset (E-GEOD-49481), including both familial and sporadic breast cancers. For microRNA validation, an independent set of 19 familial and 10 sporadic breast cancers was used. Microarray analysis identified a signature of 28 deregulated miRNAs. For our validation analyses by real time PCR, we focused on miR-92a-1*, miR-1184 and miR-943 because associated to TGF-β signalling pathway, ATM and BRCA1 genes expression. Our results highlighted alterations in miR-92a-1*, miR-1184 and miR-943 expression levels suggesting their involvement in repair of DNA double-strand breaks through TGF-beta pathway control.

  15. 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.

  16. Ovarian cancer patients at high risk of BRCA mutation: the constitutional genetic characterization does not change prognosis.

    Science.gov (United States)

    Sabatier, Renaud; Lavit, Elise; Moretta, Jessica; Lambaudie, Eric; Noguchi, Tetsuro; Eisinger, François; Cherau, Elisabeth; Provansal, Magali; Livon, Doriane; Rabayrol, Laetitia; Popovici, Cornel; Charaffe-Jauffret, Emmanuelle; Sobol, Hagay; Viens, Patrice

    2016-10-01

    Ovarian neoplasms secondary to germline BRCA mutations had been described to have a more favourable survival. There is only few data concerning the prognosis of non mutated patients presenting clinical features evocative of BRCA alterations. We retrospectively collected data from patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. Patients considered at high risk of BRCA mutation were tested for BRCA1/2 germline mutations. We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression-free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall survival (OS) of 151.2 versus 122.5 months (p = 0.52). Personal history of breast cancer increased both PFS [HR = 0.45 (95CI 0.25-0.81)] and OS [HR = 0.35 (95CI 0.16-0.75)]. In multivariate analysis, this parameter was an independent prognostic feature, whereas the identification of a BRCA1/2 mutation was not. In our cohort, all patients at high risk of BRCA mutation share a similar prognosis, whatever is their germline mutation status. Prognosis seems to be more influenced by clinical history than by germline mutations identification. If it is confirmed in larger and independent series, this result suggests that the hypothesis of other BRCA pathway alterations (BRCAness phenotype) deserves to be deeply explored.

  17. 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...

  18. Family history of the cancer on the survival of the patients with gastrointestinal cancer in northern Iran, using frailty models

    Directory of Open Access Journals (Sweden)

    Rasouli Mahboobeh

    2011-10-01

    Full Text Available Abstract Background Gastrointestinal (GI tract cancer is one of the common causes of the mortality due to cancer in most developing countries such as Iran. The digestive tract is the major organ involved in the cancer. The northern part of the country, surrounded the Caspian Sea coast, is well known and the region with highest regional incidence of the GI tract cancer. In this paper our aim is to study the most common risk factors affecting the survival of the patients suffering from GI tract cancer using parametric models with frailty. Methods This research was a prospective study. Information of 484 cases with GI cancer was collected from Babol Cancer Registration Center during 1990-1991. The risk factors we studied are age, sex, family history of cancer, marital status, smoking status, occupation, race, medication status, education, residence (urban, rural, type of cancer, migration status (indigenous, non-native. The studied cases were followed up until 2006 for 15 years. Hazard ratio was used to interpret the death risk. The effect of the factors in the study on the patients survival are studied under a family of parametric models including Weibull, Exponential, Log-normal, and the Log-logistic model. The models are fitted using with and without frailty. The Akaike information criterion (AIC was considered to compare between competing models. Results Out of 484 patients in the study, 321 (66.3% were males and 163 (33.7% were females. The average age of the patient at the time of the diagnosis was 59 yr and 55 yr for the males and females respectively. Furthermore, 359 (74.2% patients suffered from esophageal, 110 (22.7% patients recognized with gastric, and 15 (3.1% patients with colon cancer. Survival rates after 1, 3, and 5 years of the diagnosis were 24%, 16%, and 15%, respectively. We found that the family history of the cancer is a significant factor on the death risk under all statistical models in the study. The comparison of AIC

  19. A population-based study of the quality of life of cancer survivors and their family caregivers.

    Science.gov (United States)

    Mellon, Suzanne; Northouse, Laurel L; Weiss, Linda K

    2006-01-01

    Although survival rates for all cancers continue to increase, few studies have examined the quality of life of both cancer survivors and family caregivers during the survivorship period after treatment has ended. Information is lacking on the stressors, resources, meaning, and quality of life reported by survivors and family caregivers and the interrelationship between survivors' and family caregivers' quality of life. A stratified, random sample of 123 cancer survivors and 123 family caregivers (N = 246) were interviewed in an exploratory, cross-sectional design 1-6 years after cancer treatment had ended. Approximately half (N = 62) of the dyads were white and half (N = 61) were African American. Results indicated that cancer survivors reported significantly higher quality of life, less fear of cancer recurrence, and more support than their family caregivers. The strongest predictors for cancer survivors' quality of life were family stressors, social support, meaning of the illness, and employment status, whereas the strongest predictors for family caregivers' quality of life were fear of recurrence and social support. Both the survivor's and family caregiver's quality of life independently contributed to the other's quality of life. Findings from this study suggest the importance of including both survivors and family caregivers in programs of care.

  20. 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.

  1. Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases

    OpenAIRE

    Brozek, Izabela; Ratajska, Magdalena; Piatkowska, Magdalena; Kluska, Anna; Balabas, Aneta; Dabrowska, Michalina; Nowakowska, Dorota; Niwinska, Anna; Rachtan, Jadwiga; Steffen, Jan; Limon, Janusz

    2012-01-01

    It is estimated that about 5–10% of ovarian and 2–5% of all breast cancer patients are carriers of a germline BRCA1 or BRCA2 gene mutation. Most families with detected BRCA1 or BRCA2 gene mutation are qualified for molecular testing on the basis of family history of breast or ovarian cancers. The purpose of our study was to establish the frequency of positive family history of cancer in a series of Polish consecutive breast and ovarian cancer patients in two groups, with and without the BRCA1...

  2. 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

  3. Cancer preventive and curative attributes of plants of the Cactaceae family: a review.

    Science.gov (United States)

    Harlev, Eli; Nevo, Eviatar; Solowey, Elaine; Bishayee, Anupam

    2013-06-01

    The ever-increasing occurrence of cancer and the severe side effects and limited efficacy of current cancer chemotherapy based on chemical drugs shift the attention toward drugs of plant origin. The Cactaceae family comprises more than 1500 species, but until recently only a few of them have been tested for their chemopreventive and anticancer attributes, leaving a wide unexplored area still waiting for researchers to investigate. Considering this fact, and also the promising results obtained with the relatively few plants of this family already tested, it should justly be expected that some plants of the Cactaceae family yet unexplored might possess outstanding anticancer attributes, exceeding those displayed by the plants already tested. This review presents in vitro and in vivo experimental evidence on cancer chemopreventive and therapeutic potential of bioactive phytoconstituents and extracts derived from cactus plants. It also examines the underlying biochemical and molecular mechanisms involved in the antineoplastic effects of plants of the Cactaceae family. Current limitation and future directions of research towards effective use of cacti to develop efficient and side effect-free future cancer-preventive and anticancer drugs are also discussed.

  4. 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

    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. Surveillan...

  5. 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

  6. 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

  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 Well with Advanced Cancer: A Serial Qualitative Interview Study with Patients and Family Carers

    Science.gov (United States)

    Roberts, Diane; Appleton, Lynda; Calman, Lynn; Large, Paul; Lloyd-Williams, Mari; Grande, Gunn

    2017-01-01

    Objectives To understand successful strategies used by people to cope well when living with advanced cancer; to explore how professionals can support effective coping strategies; to understand how to support development of effective coping strategies for patients and family carers. Design Qualitative serial (4–12 week intervals) interview study with people with advanced cancer and their informal carers followed by focus groups. The iterative design had a novel focus on positive coping strategies. Interview analysis focused on patients and carers as individuals and pairs, exploring multiple dimensions of their coping experiences. Focus group analysis explored strategies for intervention development. Participants 26 people with advanced (stage 3–4) breast, prostate, lung or colorectal cancer, or in receipt of palliative care, and 24 paired nominated informal/family carers. Setting Participants recruited through outpatient clinics at two tertiary cancer centres in Merseyside and Manchester, UK, between June 2012 and July 2013. Results 45 patient and 41 carer interviews were conducted plus 4 focus groups (16 participants). People with advanced cancer and their informal/family carers develop coping strategies which enable effective management of psychological wellbeing. People draw from pre-diagnosis coping strategies, but these develop through responding to the experience of living with advanced cancer. Strategies include being realistic, indulgence, support, and learning from others, which enabled participants to regain a sense of wellbeing after emotional challenge. Learning from peers emerged as particularly important in promoting psychological wellbeing through the development of effective ‘everyday’, non-clinical coping strategies. Conclusions Our findings challenge current models of providing psychological support for those with advanced cancer which focus on professional intervention. It is important to recognise, enable and support peoples’ own

  9. 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.

  10. Interaction of dietary fatty acids with tumour necrosis factor family cytokines during colon inflammation and cancer.

    Science.gov (United States)

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

    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 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 NF κ B 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.

  11. 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.

  12. 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.

  13. 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

    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......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...

  14. Health and work in the family: Evidence from spouses' cancer diagnoses.

    Science.gov (United States)

    Jeon, Sung-Hee; Pohl, R Vincent

    2017-01-20

    Using Canadian administrative data from multiple sources, we provide the first nationally representative estimates for the effect of spouses' cancer diagnoses on individuals' employment and earnings and on family income. Our identification strategy exploits unexpected health shocks and combines matching with individual fixed effects in a generalized difference-in-differences framework to control for observable and unobservable heterogeneity. While the effect of spousal health shocks on labor supply is theoretically ambiguous, we find strong evidence for a decline in employment and earnings of individuals whose spouses are diagnosed with cancer. We interpret this result as individuals reducing their labor supply to provide care to their sick spouses and to enjoy joint leisure. Family income substantially declines after spouses' cancer diagnoses, suggesting that the financial consequences of such health shocks are considerable.

  15. MTA family of transcriptional metaregulators in mammary gland morphogenesis and breast cancer.

    Science.gov (United States)

    Singh, Rajesh R; Kumar, Rakesh

    2007-09-01

    Since breast cancer and its associated metastasis are a global health problem and a major cause of mortality among women, research efforts to understand the development, morphogenesis, and functioning of the mammary gland are a high priority. Myriad signaling pathways, transcription factors, and associated transcriptional coregulators have been identified in both normal functioning and neoplastic transformation of the mammary gland. The discovery of the metastasis tumor antigen 1 (MTA1) gene, its overexpression in cancer and metastasis and its subsequent identification as an integral part of the chromatin remodeling complex heralded extensive research on its physiological role. Subsequent identification of additional gene family members, namely MTA1s, MTA2, and MTA3, and their functions in the cell has resulted in the establishment of the significance of the MTA family. The role of these proteins in modulating hormonal responses in normal mammary glands and in breast cancer has resulted in their identification as important molecular markers and potential therapeutic targets.

  16. 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.

  17. VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.

    Science.gov (United States)

    Saponaro, Concetta; Malfettone, Andrea; Ranieri, Girolamo; Danza, Katia; Simone, Giovanni; Paradiso, Angelo; Mangia, Anita

    2013-01-01

    Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is known that there is an interaction between HIF-1α and BRCA1 carrier cancers, but little has been reported about angiogenesis in BRCA1-2 carrier and BRCAX breast cancers. In this study, we investigated the expression of VEGF and HIF-1α and microvessel density (MVD) in 26 BRCA1-2 carriers and 58 BRCAX compared to 77 sporadic breast cancers, by immunohistochemistry. VEGF expression in BRCA1-2 carriers was higher than in BRCAX cancer tissues (p = 0.0001). Furthermore, VEGF expression was higher in both BRCA1-2 carriers and BRCAX than the sporadic group (p<0.0001). VEGF immunoreactivity was correlated with poor tumor grade (p = 0.0074), hormone receptors negativity (p = 0.0206, p = 0.0002 respectively), and MIB-1-labeling index (p = 0.0044) in familial cancers (BRCA1-2 and BRCAX). The percentage of nuclear HIF-1α expression was higher in the BRCA1-2 carriers than in BRCAX cancers (p<0.05), and in all familial than in sporadic tumor tissues (p = 0.0045). A higher MVD was observed in BRCA1-2 carrier than in BRCAX and sporadic cancer tissues (p = 0.002, p = 0.0001 respectively), and in all familial tumors than in sporadic tumors (p = 0.01). MVD was positively related to HIF-1α expression in BRCA1-2 carriers (r = 0.521, p = 0.006), and, in particular, we observed a highly significant correlation in the familial group (r = 0.421, p<0.0001). Our findings suggest that angiogenesis plays a crucial role in BRCA1-2 carrier breast cancers. Prospective studies in larger BRCA1-2 carrier series are needed to improve the best therapeutic strategies for this subgroup of breast cancer patients.

  18. 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......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...... 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...

  19. 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.

  20. The complexity of cancer in multiple family members: dynamics of social work collaboration.

    Science.gov (United States)

    Snow, Alison; Gilbertson, Kristen

    2011-01-01

    This article presents a case study of one family affected by a cancer diagnosis in both the father and the daughter, who were diagnosed within the same time interval and who underwent treatment at the same time. The article examines the relationship between the caregivers and the oncology patient as well as with one another when the stress of diagnosis is compounded by multiple, simultaneous, and similar diagnoses in a highly condensed period of time. A thorough examination of the literature reveals that there are significant gaps regarding how multiple cancer diagnoses in one family affect the family dynamic, individual and collective coping styles, and caregiver burden. The diagnoses can also dramatically exacerbate economic stressors in a family. The coordination of psychosocial care from the perspectives of the adult and pediatric oncology social workers at an urban academic medical center will be discussed. The social work role, importance of collaboration, and family centered care perspective will be discussed as a method of easing the treatment experience for families in psychosocial distress.

  1. 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.

  2. Angiogenetic axis angiopoietins/Tie2 and VEGF in familial breast cancer.

    Science.gov (United States)

    Danza, K; Pilato, B; Lacalamita, R; Addati, T; Giotta, F; Bruno, A; Paradiso, A; Tommasi, S

    2013-08-01

    Angiogenesis leads to the formation of blood vessels from pre-existing ones, allowing tumor growth. Vascular endothelial growth factor (VEGF) and Angiopoietins (Ang-1, Ang-2) have a pivotal role in tumor angiogenesis but few data regarding their role in hereditary breast cancer are available. The aim of the present study was to analyze Ang-1, Ang-2, tyrosine-protein kinase receptor Tie2 and VEGF expression and their correlation in a cohort of familial and sporadic breast cancers in order to verify whether the presence of germline mutations in BRCA may have a role in tumor microenvironment regulation. Tumor samples from a cohort of 41 patients with a first diagnosis and a family history of breast cancer and 19 patients with sporadic breast cancers were enrolled. The expression of Tie2, Ang-1, Ang-2 and VEGF were analyzed by quantitative real-time PCR. Patients harboring BRCA mutations had higher levels of Ang-1 (P=0.05), Ang-2 (P=0.02) and VEGF (P=0.04) mRNA compared with those without BRCA mutations (BRCAX). The same was observed in triple-negative breast cancer (TNBC). Moreover, a positive correlation between Ang-2 and VEGF was found in both the familial breast cancer group (BRCA carriers: r=0.83; P<0.0001 and BRCAX: r=0.58; P=0.008) and in TNBC (r=0.62; P=0.007). The higher levels of Ang-1, Ang-2 and VEGF mRNA found in BRCA carriers and TNBCs suggest that they could be attractive angiogenic therapeutic targets in these breast cancers.

  3. The transtheoretical model, health belief model, and breast cancer screening among Iranian women with a family history of breast cancer

    Directory of Open Access Journals (Sweden)

    Ziba Farajzadegan

    2016-01-01

    Full Text Available Background: Participation of Iranian women with a family history of breast cancer in breast cancer screening programs is low. This study evaluates the compliance of women having a family history of breast cancer with clinical breast exam (CBE according to the stage of transtheoretical model (TTM and health belief model (HBM. Materials and Methods: In this cross-sectional study, we used Persian version of champion's HBM scale to collect factors associated with TTM stages applied to screening from women over 20 years and older. The obtained data were analyzed by SPSS, using descriptive statistics, Chi-square test, independent t-test, and analysis of covariance. Results: Final sample size was 162 women. Thirty-three percent were in action/maintenance stage. Older women, family history of breast cancer in first-degree relatives, personal history of breast disease, insurance coverage, and a history of breast self-examination were associated with action/maintenance stage. Furthermore, women in action/maintenance stages had significantly fewer perceived barriers in terms of CBE in comparison to women in other stages (P < 0.05. There was no significant difference in other HBM subscales scores between various stages of CBE screening behavior (P < 0.05. Conclusion: The finding indicates that the rate of women in action/maintenance stage of CBE is low. Moreover, results show a strong association between perceived barriers and having a regular CBE. These clarify the necessity of promoting national target programs for breast cancer screening, which should be considered as the first preference for reducing CBE barriers.

  4. 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.

  5. BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics.

    Science.gov (United States)

    Wagner, T M; Möslinger, R A; Muhr, D; Langbauer, G; Hirtenlehner, K; Concin, H; Doeller, W; Haid, A; Lang, A H; Mayer, P; Ropp, E; Kubista, E; Amirimani, B; Helbich, T; Becherer, A; Scheiner, O; Breiteneder, H; Borg, A; Devilee, P; Oefner, P; Zielinski, C

    1998-07-29

    We identified 17 BRCA1 mutations in 86 Austrian breast and ovarian cancer families (20%) that were screened for mutations by denaturing high-performance liquid chromatography (DHPLC) and the protein truncation test (PTT). Eleven distinct mutations were detected, 4 of them (962del4, 2795del4, 3135del4 and L3376stop) not previously reported in families of non-Austrian origin. In addition, 6 rare missense mutations (allele frequency Cys61Gly (3 times) 5382insC (2 times) and Q1806stop (2 times). Haplotype analysis of the 4 recurrent mutations suggested a common ancestor for each of these. Thirty-four breast cancer cases from 17 families with BRCA1 mutations were further analyzed. We observed a low median age of onset (39.5 years). Sixty-eight percent of all BRCA1 breast cancer cases had negative axillary lymph nodes. This group showed a significant prevalence of a negative estrogen and progesterone receptor status and stage I tumors compared with an age-related, node-negative control group. The prevalence of grade III tumors was marginally significant. Survival analysis either with a control group matched for age (within 5 years), grade, histologic subtype and estrogen receptor status, or with an age-related, node-negative comparison group, showed no statistical difference.

  6. Breast cancer in younger women: effects on interpersonal and family relations.

    Science.gov (United States)

    Northouse, L L

    1994-01-01

    Although breast cancer can have a stressful impact on women of all ages, young women may be particularly vulnerable to the negative effects of the disease. Based on a developmental perspective, this article reviews studies on the emotional impact of breast cancer on young women, their spouses, children, and the marital relationship. Studies indicate that younger women experience more emotional distress than older women, although the inverse relationship between age and emotional distress is not consistent across all studies. Although age does not appear to have a direct relationship to husbands' adjustments, younger husbands reported more problems carrying out domestic roles and a greater number of life stresses than older husbands. Studies on the impact of breast cancer on children are limited in number and scope but indicate that the effects of breast cancer vary according to the developmental level of the child. Directions for further research on young women and their families are suggested.

  7. 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.

  8. 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.

  9. 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.

  10. Expression of IAP family proteins and its clinical importance in breast cancer patients.

    Science.gov (United States)

    Pluta, P; Jeziorski, A; Cebula-Obrzut, A Pluta B; Wierzbowska, A; Piekarski, J; Smolewski, P

    2015-01-01

    Inhibitor of apoptosis (IAP) family proteins is involved in mechanisms of resistance to apoptosis in various cancer cells. The aim of this study was to assess the expression of selected IAP proteins such as XIAP, cIAP-1, cIAP-2 and survivin in breast cancer patients and evaluates their relationship with the prognostic and predictive factors and their impact to overall survival (OS) and progression free survival (PFS). The study was conducted with the use of tissue samples prospectively collected from 92 previously untreated female breast cancer patients. The control encompassed 10 fibroadenoma patients. The expression of XIAP, cIAP-1, cIAP-2 and survivin was assessed using flow multicolor cytometry. XIAP expression was present in 99 % of the breast cancer patients (91/92) with the median expression 13.65% (range 1-66.8%). Expression of XIAP in breast cancer was significantly higher compared to the control group (p=0.006). Median expression of cIAP-1, cIAP-2 and survivin in the study group was 25.95% (range 0.8-83.7%), 16.7% (range 1-53.2%) and 4.6% (range 0-43%) respectively. In the rank Spearman test, strong correlations (pproteins and survival. However, low expression of XIAP in breast cancer showed trend to longer PFS (p=0.08). XIAP, cIAP-1 cIAP-2 and survivin participate in antiapoptotic mechanisms in breast cancer and XIAP and survivin seem to have the most significant prognostic importance. Further studies are needed to establish more complete prognostic and predictive values of IAP family proteins in breast cancer patients.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Environmental, occupational and familial risks for testicular cancer: a hospital-based case-control study.

    Science.gov (United States)

    Walschaerts, Marie; Muller, Audrey; Auger, Jacques; Bujan, Louis; Guérin, Jean-François; Le Lannou, Dominique; Clavert, André; Spira, Alfred; Jouannet, Pierre; Thonneau, Patrick

    2007-08-01

    Testicular cancer (TC) risk factors remain largely unknown, except for personal history of cryptorchidism and familial history of TC. We conducted a hospital-based case-control study on familial, environmental and occupational conditions in which we compared 229 cases and 800 controls. TC was correlated with cryptorchidism (OR = 3.02; CI: 1.90-4.79), a history of cryptorchidism in relatives (OR = 2.85; CI: 1.70-4.79), and TC (OR = 9.58; CI: 4.01-22.88], prostate cancer (OR = 1.80; CI: 1.08-3.02) and breast cancer (OR = 1.77; CI: 1.20-2.60) in relatives. Living in a rural area or having regular gardening activity (growing fruit or vegetables) was associated with an increased risk of TC (OR = 1.63; CI: 1.16-2.29; OR = 1.84; CI: 1.23-2.75). Regarding occupation, we found a relationship with employment in metal trimming (OR = 1.96; CI: 1.00-3.86), chemical manufacture (OR = 1.88; CI: 1.14-3.10), industrial production of glue (OR = 2.21; CI: 1.15-4.25), and welding (OR = 2.84; CI: 1.51-5.35). In a multivariate model, only a history of cryptorchidism in the men, cryptorchidism in relatives, TC, and breast cancer remained significant. Our findings contribute further evidence to a pattern of TC risk factors, which include the significant weight of personal reproductive history and also of testicular and breast cancer in relatives. By including in a multivariate model variables linked to environmental and occupational exposure and related to familial cancer history, neither living in a rural area nor any occupational exposure appeared to be a potential environmental TC risk factor.

  13. p53 family members - important messengers in cell death signaling in photodynamic therapy of cancer?

    Science.gov (United States)

    Acedo, Pilar; Zawacka-Pankau, Joanna

    2015-08-01

    TP53 is one of the genes most frequently inactivated in cancers. Mutations in TP53 gene are linked to worse prognosis and shorter overall survival of cancer patients. TP53 encodes a critical tumor suppressor, which dictates cell fate decisions upon stress stimuli. As a sensor of cellular stress, p53 is a relevant messenger of cell death signaling in ROS-driven photodynamic therapy (PDT) of cancer. The significant role of p53 in response to PDT has been reported for several clinically approved photosensitizers. Multiple reports described that wild-type p53 contributes to cell killing upon photodynamic therapy with clinically approved photosensitizers but the mechanism is still not fully understood. This work outlines the diverse functions of p53 family members in cancer cells' susceptibility and resistance to PDT. In summary p53 and p53 family members are emerging as important mediators of cell death signaling in photodynamic therapy of cancer, however the mechanism of cell death provoked during PDT might differ depending on the tissue type and the photosensitizer applied.

  14. Evolution of the mir-155 family and possible targets in cancers and the immune system.

    Science.gov (United States)

    Xie, Guang-Bing; Liu, Wei-Jia; Pan, Zhi-Jun; Cheng, Tian-Yin; Luo, Chao

    2014-01-01

    The mir-155 family is not only involved in a diversity of cancers, but also as a regulator of the immune system. However, the evolutionary history of this family is still unclear. The present study indicates that mir-155 evolved independently with lineage-specific gain of miRNAs. In addition, arm switching has occurred in the mir-155 family, and alternative splicing could produce two different lengths of ancestral sequences, implying the alternative splicing can also drive evolution for intragenic miRNAs. Here we screened validated target genes and immunity- related proteins, followed by analyzation of the mir-155 family function by high-throughput methods like the gene ontology (GO) and Kyoto Eneyclopedin of Genes and Genemes (KEGG) pathway enrichment analysis. The high-throughput analysis showed that the CCND1 and EGFR genes were outstanding in being significantly enriched, and the target genes cebpb and VCAM1 and the protein SMAD2 were also vital in mir-155-related immune reponse activities. Therefore, we conclude that the mir-155 family is highly conserved in evolution, and CCND1 and EGFR genes might be potential targets of mir-155 with regard to progress of cancers, while the cebpb and VCAM1 genes and the protein SMAD2 might be key factors in the mir-155 regulated immune activities.

  15. Penetrance of colorectal cancer among MLH1/MSH2 carriers participating in the colorectal cancer familial registry in Ontario

    Directory of Open Access Journals (Sweden)

    Choi Yun-Hee

    2009-08-01

    Full Text Available Abstract Background Several DNA mismatch repair (MMR genes, responsible for the majority of Lynch Syndrome cancers, have been identified, predominantly MLH1 and MSH2, but the risk associated with these mutations is still not well established. The aim of this study is to provide population-based estimates of the risks of colorectal cancer (CRC by gender and mutation type from the Ontario population. Methods We analyzed 32 families segregating MMR mutations selected from the Ontario Familial Colorectal Cancer Registry and including 199 first-degree and 421 second-degree relatives. The cumulative risks were estimated using a modified segregation-based approach, which allows correction for the ascertainment of the Lynch Syndrome families and permits account to be taken for missing genotype information. Results The risks of developing CRC by age 70 were 60% and 47% among men and women carriers of any MMR mutation, respectively. Among MLH1 mutation carriers, males had significantly higher risks than females at all ages (67% vs. 35% by age 70, p-value = 0.02, while the risks were similar in MSH2 carriers (about 54%. The relative risk associated with MLH1 was almost constant with age (hazard ratio (HR varied between 5.5-5.1 over age 30–70, while the HR for MSH2 decreased with age (from 13.1 at age 30 to 5.4 at age 70. Conclusion This study provides a unique population-based study of CRC risks among MSH2/MLH1 mutation carriers in a Canadian population and can help to better define and understand the patterns of risks among members of Lynch Syndrome families.

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

    Directory of Open Access Journals (Sweden)

    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

  18. HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer

    OpenAIRE

    Weeks, Alexia L.; Scott G Wilson; Ward, Lynley; Goldblatt, Jack; Hui, Jennie; Walsh, John P.

    2016-01-01

    Background The genetic basis of nonsyndromic familial nonmedullary thyroid cancer (FNMTC) is poorly understood. A recent study identified HABP2 as a tumor suppressor gene and identified a germline variant (G534E) in an extended FNMTC kindred. The relevance of this to other FNMTC kindreds is uncertain. Methods Sanger sequencing was performed on peripheral blood DNA from probands from 37 Australian FNMTC kindreds to detect the G534E variant. Whole exome data from 59 participants from 20 kindred...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Masood, Ashiq [Department of Internal Medicine/Pathology, Karmanos Cancer Institute, Wayne State University, 4100 John R, HWCRC 732, Detroit, MI 48201 (United States); Azmi, Asfar S. [Department of Pathology, Karmanos Cancer Institute, Wayne State University, 4100 John R, HWCRC 732, Detroit MI 48201 (United States); Mohammad, Ramzi M., E-mail: mohammar@karmanos.org [Department of Internal Medicine/Pathology, Karmanos Cancer Institute, Wayne State University, 4100 John R, HWCRC 732, Detroit, MI 48201 (United States); Department of Oncology, Karmanos Cancer Institute, 4100 John R, HWCRC 732, Detroit, MI 48201 (United States)

    2011-03-24

    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.

  4. 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.

  5. Identification of Patients with Family History of Pancreatic Cancer--Investigation of an NLP System Portability.

    Science.gov (United States)

    Mehrabi, Saeed; Krishnan, Anand; Roch, Alexandra M; Schmidt, Heidi; Li, DingCheng; Kesterson, Joe; Beesley, Chris; Dexter, Paul; Schmidt, Max; Palakal, Mathew; Liu, Hongfang

    2015-01-01

    In this study we have developed a rule-based natural language processing (NLP) system to identify patients with family history of pancreatic cancer. The algorithm was developed in a Unstructured Information Management Architecture (UIMA) framework and consisted of section segmentation, relation discovery, and negation detection. The system was evaluated on data from two institutions. The family history identification precision was consistent across the institutions shifting from 88.9% on Indiana University (IU) dataset to 87.8% on Mayo Clinic dataset. Customizing the algorithm on the the Mayo Clinic data, increased its precision to 88.1%. The family member relation discovery achieved precision, recall, and F-measure of 75.3%, 91.6% and 82.6% respectively. Negation detection resulted in precision of 99.1%. The results show that rule-based NLP approaches for specific information extraction tasks are portable across institutions; however customization of the algorithm on the new dataset improves its performance.

  6. Family History

    Science.gov (United States)

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  7. Nursing in the home palliative care: the view of a family member of a patient with cancer

    Directory of Open Access Journals (Sweden)

    Aline Lima Ribeiro

    2014-09-01

    Full Text Available This study aimed to understand the concepts of family members of patients with cancer, who were inserted and guided by the actions of an extension project aimed at patients with cancer and their families, about the home care given to them, during the treatment phase and progression of the disease. This is an evaluative qualitative research conducted with six family members from June to October, 2013, through semi-structured interviews, analyzed by the method of content analysis. Three categories emerged: the support of nurses in coping with the disease, creating a bond with the patients and their families and nursing as a link to social support networks. It was understood that the health monitoring in the home context gave to the families and patients support and safety to handle concerns that cancer brought into their lives.

  8. Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain)

    OpenAIRE

    Blay, Pilar; Santamaría, Iñigo; Pitiot, Ana S.; Luque, María; Alvarado, Marta G; Lastra, Ana; Fernández, Yolanda; Paredes, Ángeles; Freije, José MP; Balbín, Milagros

    2013-01-01

    Background The prevalence of BRCA1 and BRCA2 mutations in Spain is heterogeneous and varies according to geographical origin of studied families. The contribution of these mutations to hereditary breast and ovarian cancer has not been previously investigated in Asturian populations (Northern Spain). Methods In the present work, 256 unrelated high-risk probands with breast and/or ovarian cancer from families living in Asturias were analyzed for the presence of a BRCA1 or BRCA2 gene mutation fr...

  9. Knowledge about hereditary cancer of women with family histories of breast, colorectal, or both types of cancer.

    Science.gov (United States)

    Campacci, N; de Lima, J O; Ramadan, L; Palmero, E I

    2015-03-01

    Usually, the mass media do not address hereditary cancer and their risk factors, nor are these topics discussed at the community level. We used an informative guide on cancer and hereditary cancer, followed by a questionnaire on these topics to investigate the relevant knowledge among women at high risk for hereditary breast and/or colorectal cancer from a population-based cohort. The cohort was composed of 81 Brazilian women with positive family histories of breast and/or colorectal cancer. Strauss and Corbin's Grounded Theory was used for qualitative analysis. The average age of the cohort was 49.9 years old. Three participants (3.9%) were illiterate, 45 (59.2%) had attended elementary school, 14 (18.4%) had secondary school, and 14 (18.4%) held higher education degrees. A total of 47 (54.3%) volunteers were unable to fully understand the information provided in the guide because they did not know the meaning of words such as metastasis, malignant, hereditary, sporadic, or oncogenetics. Notwithstanding, the acceptance of the educational tool utilized was satisfactory, and it enhanced the volunteers' interest in a better understanding of cancer and heredity. Thereby, we concluded that the low knowledge of this important subject and the unawareness about fundamental terms required for the comprehension of this specific type of neoplasm made us believe that the use of the informative guide can provide a great value when used previously to the genetic counseling consultations. Besides, educational tools of easy understanding should be part of everyday clinical practice, from primary to specialized patient care.

  10. RAD51C germline mutations in breast and ovarian cancer cases from high-risk families.

    Directory of Open Access Journals (Sweden)

    Jessica Clague

    Full Text Available BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5' UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001. Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene.

  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. DNA repair genes implicated in triple negative familial non-BRCA1/2 breast cancer predisposition.

    Science.gov (United States)

    Ollier, Marie; Radosevic-Robin, Nina; Kwiatkowski, Fabrice; Ponelle, Flora; Viala, Sandrine; Privat, Maud; Uhrhammer, Nancy; Bernard-Gallon, Dominique; Penault-Llorca, Frédérique; Bignon, Yves-Jean; Bidet, Yannick

    2015-01-01

    Among breast cancers, 10 to 15% of cases would be due to hereditary risk. In these familial cases, mutations in BRCA1 and BRCA2 are found in only 15% to 20%, meaning that new susceptibility genes remain to be found. Triple-negative breast cancers represent 15% of all breast cancers, and are generally aggressive tumours without targeted therapies available. Our hypothesis is that some patients with triple negative breast cancer could share a genetic susceptibility different from other types of breast cancers. We screened 36 candidate genes, using pyrosequencing, in all the 50 triple negative breast cancer patients with familial history of cancer but no BRCA1 or BRCA2 mutation of a population of 3000 families who had consulted for a familial breast cancer between 2005 and 2013. Any mutations were also sequenced in available relatives of cases. Protein expression and loss of heterozygosity were explored in tumours. Seven deleterious mutations in 6 different genes (RAD51D, MRE11A, CHEK2, MLH1, MSH6, PALB2) were observed in one patient each, except the RAD51D mutation found in two cases. Loss of heterozygosity in the tumour was found for 2 of the 7 mutations. Protein expression was absent in tumour tissue for 5 mutations. Taking into consideration a specific subtype of tumour has revealed susceptibility genes, most of them in the homologous recombination DNA repair pathway. This may provide new possibilities for targeted therapies, along with better screening and care of patients.

  13. 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...

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes

    NARCIS (Netherlands)

    Ruijs, M.W.G.; Verhoef, S.; Rookus, M.A.; Pruntel, R.; van der Hout, A.H.; Hogervorst, F.B.L.; Kluijt, I.; Sijmons, R.H.; Aalfs, C.M.; Wagner, A.; Ausems, M.G.E.M.; Hoogerbrugge, N.; van Asperen, C.J.; Gómez García, E.B.; Meijers-Heijboer, H.; ten Kate, L.P.; Menko, F.H.; van 't Veer, L.J.

    2010-01-01

    Background Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome. Most families fulfilling the classical diagnostic criteria harbour TP53 germline mutations. However, TP53 germline mutations may also occur in less obvious phenotypes. As a result, different criteria a

  2. 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.

  3. 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

  4. Differences in the progesterone receptor contents between familial breast cancers and sporadic breast cancers stratified by patient age.

    Science.gov (United States)

    Fukutomi, T; Akashi-Tanaka, S

    2001-01-01

    In the present study, we investigated the estrogen (ER) and progesterone receptor (PR) contents of familial breast cancers (FBCs) and compared the findings with those of sporadic breast cancers., stratified by the patients' age. To evaluate the hormone receptor contents of Japanese FBCs, we collected a consecutive series of 250 FBCs and 2,533 sporadic breast cancers (SBCs). These patients were divided into the three groups stratified by the patients' age at initial surgery (group I, under 40 years old; group II, 40-60 years old; group III, over 60 years old). The clinicopathological features of FBCs and SBCs, including ERs and PRs, were analyzed for each group. In all age groups, the PR contents of FBCs were significantly lower than those of SBCs, particularly for group III. In FBCs, the PR content was significantly lower in group III than in groups I or II. In addition, there was a nonsignificant trend towards a high frequency of ER-positive, PR-negative tumors in FBC patients aged 60 years and over. These data indicate that the loss of ER function and/or loss of binding capacity of PR to progesterone was associated with some late-onset FBCS.

  5. 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.

  6. Research with families facing cancer: the challenges of accrual and retention.

    Science.gov (United States)

    Northouse, Laurel L; Rosset, Tansey; Phillips, Laurel; Mood, Darlene; Schafenacker, Ann; Kershaw, Trace

    2006-06-01

    The purposes of this article are: (a) to describe and analyze the accrual and retention patterns in a longitudinal randomized clinical trial with prostate cancer patients and their partners, and (b) to discuss strategies that were used to overcome challenges in conducting this family-based study. Initially, 429 dyads were referred to the study. Of these, 166 were not enrolled due to refusal (n = 120) or ineligibility (n = 46), 21 of whom did not meet one or more of the inclusion criteria, and 25 of whom could not be reached within the 2-month window of eligibility. Of the 383 eligible dyads, 263 dyads were enrolled (enrollment rate of 68.7%). Accrual and retention patterns differed by research site, referral procedures, and phase of prostate cancer. The retention rate was very good with the majority of dyads (n = 218) completing all three follow-up assessments at 4, 8, and 12 months (82.9%).

  7. 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.

  8. HABP2 G534E Mutation in Familial Nonmedullary Thyroid Cancer.

    Science.gov (United States)

    Zhang, Tao; Xing, Mingzhao

    2016-06-01

    Papillary thyroid cancer (PTC) is a common endocrine malignancy, accounting for nearly 90% of all thyroid cancers. About 5% of PTC is hereditary familial nonmedullary thyroid cancer (FNMTC). No general susceptibility gene is known for FNMTC. An oncogenic HABP2 G534E mutation has been recently reported in one FNMTC kindred, suggesting that HABP2 is a susceptibility gene for FNMTC. Because of the limited kindred studied, how commonly this gene is responsible-and hence how important clinically it is-for FNMTC remains to be answered. By investigating a large number of FNMTC kindreds in the present study, we identified HABP2 G534E in several independent kindreds of FNMTC. The overall prevalence of HABP2 G534E was six per 43 (14.0%) PTC patients from the 29 kindreds and four per 29 (13.8%) kindreds. None of the subjects with benign thyroid neoplasm or the normal subjects from these kindreds had this mutation. These results are consistent with HABP2 G534E being a susceptibility gene in a subgroup of FNMTC, providing important diagnostic implications for this hereditary thyroid cancer.

  9. The HABP2 G534E Variant Is an Unlikely Cause of Familial Nonmedullary Thyroid Cancer

    OpenAIRE

    Sahasrabudhe, R; Stultz, J; Williamson, J; Lott, P; A. Estrada; Bohorquez, M; Palles, C; Polanco-Echeverry, G; Jaeger, E; Martin, L.; Magdalena Echeverry, M; Tomlinson, I.; Carvajal-Carmona, LG; TCUKIN,

    2016-01-01

    A recent study reported the non-synonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial non-medullary thyroid cancer (NMTC).The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multi-center population based study of NMTC cases from the British Isles.A case-control analysis of rs7080536 genotypes was performed using 2,105 TCUKIN cases and 5,172 UK controls.Cases comprised 2,105 NMTC cases. Patients sub-groups with papill...

  10. 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.

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

    Science.gov (United States)

    Petersen, Steffen; Neves-Petersen, Maria Teresa; Olsen, Birgitte

    2008-02-01

    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 over expressing the EGF receptor, lead to arrest of the EGFR signaling pathway. We have investigated the available sequence and experimental 3D structures available in the Protein Data Bank. The EGF receptor contains a Furin like cystein rich extracellular domain. The cystein content is highly unusual, 25 disulphide bridges supports the 621 amino acid extracellular protein domain scaffold (1mb6.pdb). In two cases a tryptophan is neighboring a cystein in the primary sequence, which in itself is a rare observation. Aromatic residues is observed to be spatially close to all observed 25 disulphide 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 disulphide bridges in proteins upon illumination of nearby aromatic amino acids was the first step that lead to the hypothesis that UV light could modulate the structure and therefore the function of these key receptor proteins. The observation that membrane receptors (EGFR) contained exactly the motifs 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.

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

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    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.

  13. 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

    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....... 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-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...

  14. Cisplatin resistance by induction of aldo-keto reductase family 1 member C2 in human bladder cancer cells

    OpenAIRE

    Shirato, Akitomi; KIKUGAWA, TADAHIKO; Miura, Noriyoshi; Tanji, Nozomu; Takemori, Nobuaki; Higashiyama, Shigeki; Yokoyama, Masayoshi

    2013-01-01

    Cisplatin is currently the most effective anti-tumor agent available against bladder cancer. To clarify the mechanism underlying cisplatin resistance in bladder cancer, the present study examined the role of the aldo-keto reductase family 1 member C2 (AKR1C2) protein on chemoresistance using a human bladder cancer cell line. The function of AKR1C2 in chemoresistance was studied using the human HT1376 bladder cancer cell line and the cisplatin-resistant HT1376-CisR subline. AKR1C2 was expresse...

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

    Directory of Open Access Journals (Sweden)

    Li Rita Zhang

    2012-01-01

    Full Text Available 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 cancer worry using logistic regression. Nonlinear relationships were assessed using likelihood ratio tests. Results. A significant non-linear inverted “U” relationship was observed between breast cancer worry and mammography screening (P=0.034 for all women, where women at either low or high worry levels were less likely than those at medium to have a screening mammogram. A similar significant non-linear inverted “U” relationship was also found among all women and women at low familial risk for worry and screening clinical breast examinations (CBEs. Conclusions. Medium levels of cancer worries predicted higher rates of screening mammography and CBE among high-risk women.

  16. 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.

  17. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

    Energy Technology Data Exchange (ETDEWEB)

    Benny Klimek, Margaret E.; Aydogdu, Tufan [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Link, Majik J.; Pons, Marianne [Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Koniaris, Leonidas G. [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States); Zimmers, Teresa A., E-mail: tzimmers@med.miami.edu [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States)

    2010-01-15

    Cachexia, progressive loss of fat and muscle mass despite adequate nutrition, is a devastating complication of cancer associated with poor quality of life and increased mortality. Myostatin is a potent tonic muscle growth inhibitor. We tested how myostatin inhibition might influence cancer cachexia using genetic and pharmacological approaches. First, hypermuscular myostatin null mice were injected with Lewis lung carcinoma or B16F10 melanoma cells. Myostatin null mice were more sensitive to tumor-induced cachexia, losing more absolute mass and proportionately more muscle mass than wild-type mice. Because myostatin null mice lack expression from development, however, we also sought to manipulate myostatin acutely. The histone deacetylase inhibitor Trichostatin A has been shown to increase muscle mass in normal and dystrophic mice by inducing the myostatin inhibitor, follistatin. Although Trichostatin A administration induced muscle growth in normal mice, it failed to preserve muscle in colon-26 cancer cachexia. Finally we sought to inhibit myostatin and related ligands by administration of the Activin receptor extracellular domain/Fc fusion protein, ACVR2B-Fc. Systemic administration of ACVR2B-Fc potently inhibited muscle wasting and protected adipose stores in both colon-26 and Lewis lung carcinoma cachexia, without affecting tumor growth. Enhanced cachexia in myostatin knockouts indicates that host-derived myostatin is not the sole mediator of muscle wasting in cancer. More importantly, skeletal muscle preservation with ACVR2B-Fc establishes that targeting myostatin-family ligands using ACVR2B-Fc or related molecules is an important and potent therapeutic avenue in cancer cachexia.

  18. Interventions with family caregivers of cancer patients: meta-analysis of randomized trials.

    Science.gov (United States)

    Northouse, Laurel L; Katapodi, Maria C; Song, Lixin; Zhang, Lingling; Mood, Darlene W

    2010-01-01

    Family caregivers of cancer patients receive little preparation, information, or support to perform their caregiving role. However, their psychosocial needs must be addressed so they can maintain their own health and provide the best possible care to the patient. The purpose of this article is to analyze the types of interventions offered to family caregivers of cancer patients, and to determine the effect of these interventions on various caregiver outcomes. Meta-analysis was used to analyze data obtained from 29 randomized clinical trials published from 1983 through March 2009. Three types of interventions were offered to caregivers: psychoeducational, skills training, and therapeutic counseling. Most interventions were delivered jointly to patients and caregivers, but they varied considerably with regard to dose and duration. The majority of caregivers were female (64%) and Caucasian (84%), and ranged in age from 18 to 92 years (mean age, 55 years). Meta-analysis indicated that although these interventions had small to medium effects, they significantly reduced caregiver burden, improved caregivers' ability to cope, increased their self-efficacy, and improved aspects of their quality of life. Various intervention characteristics were also examined as potential moderators. Clinicians need to deliver research-tested interventions to help caregivers and patients cope effectively and maintain their quality of life.

  19. 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.

  20. 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.

  1. Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis

    Directory of Open Access Journals (Sweden)

    Aragon Robert J

    2010-10-01

    Full Text Available Abstract Background The Ras association domain family 1 (RASSF1 gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells. Methods Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed. Results In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration in vitro. Conclusion Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.

  2. Effectiveness of an Interdisciplinary Palliative Care Intervention for Family Caregivers in Lung Cancer

    Science.gov (United States)

    Sun, Virginia; Grant, Marcia; Koczywas, Marianna; Freeman, Bonnie; Zachariah, Finly; Fujinami, Rebecca; Del Ferraro, Catherine; Uman, Gwen; Ferrell, Betty

    2015-01-01

    Background Family caregivers (FCGs) experience significant deteriorations in quality of life while caring for lung cancer patients. This study tested the effectiveness of an interdisciplinary palliative care intervention for FCGs of patients diagnosed with stage I–IV non-small cell lung cancer (NSCLC). Methods FCGs who were identified by patients as the primary caregiver were enrolled in a prospective, quasi-experimental study whereby the usual care group was accrued first followed by the intervention group. FCGs in the intervention group were presented at interdisciplinary care meetings, and they also received four educational sessions organized in the physical, psychological, social, and spiritual domains. The sessions included self-care plans to support the FCG’s own needs. Caregiver burden, caregiving skills preparedness, psychological distress, and FCG QOL were assessed at baseline and 12 weeks using validated measures. Results A total of 366 FCGs were included in the primary analysis. FCGs who received the interdisciplinary palliative care intervention had significantly better scores for social well-being (5.84 vs. 6.86; pcaregiver burden compared to FCGs in the usual care group (p=.008). Conclusions An interdisciplinary approach to palliative care in lung cancer resulted in statistically significant improvements in the FCG’s social well-being, psychological distress, and less caregiver burden. PMID:26150131

  3. 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.

  4. 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.

  5. Potential usage of ING family members in cancer diagnostics and molecular therapy.

    Science.gov (United States)

    Gunduz, Mehmet; Demircan, Kadir; Gunduz, Esra; Katase, Naoki; Tamamura, Ryo; Nagatsuka, Hitoshi

    2009-05-01

    The Inhibitor of Growth (ING) gene family is an emerging putative type II tumor suppressor gene (TSG). Proteins of INGs (ING1-5), critical modulator of the histone code via PHD fingers, are able to suppress cell growth and proliferation, induce apoptosis, and modulate cell cycle progression. ING proteins are involved in transcriptional regulation of genes, such as the p53-inducible gene p21. ING proteins also serve as shuttling proteins between nucleus and cytoplasm, and dysregulation of this nucleocytoplasmic traffic has been shown in some cancer cells. In cancer cells, ING mRNA levels are often lost or suppressed but the genes are rarely mutated. Recently the potential roles of ING proteins as prognostic biomarkers, detection of aggressive behavior of the tumor as well as prediction of chemo-radiotherapy response have also emerged. In this review, we summarize the up-to-date knowledge on functions of the ING proteins, the protein status in human tumors and discuss as a potential target in the molecular diagnostics and therapy of cancer.

  6. 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.

  7. International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation

    NARCIS (Netherlands)

    Peixoto, Ana; Santos, Catarina; Pinheiro, Manuela; Pinto, Pedro; Soares, Maria Jose; Rocha, Patricia; Gusmao, Leonor; Amorim, Antonio; van der Hout, Annemarie; Gerdes, Anne-Marie; Thomassen, Mads; Kruse, Torben A.; Cruger, Dorthe; Sunde, Lone; Bignon, Yves-Jean; Uhrhammer, Nancy; Cornil, Lucie; Rouleau, Etienne; Lidereau, Rosette; Yannoukakos, Drakoulis; Pertesi, Maroulio; Narod, Steven; Royer, Robert; Costa, Mauricio M.; Lazaro, Conxi; Feliubadalo, Lidia; Grana, Begona; Blanco, Ignacio; de la Hoya, Miguel; Caldes, Trinidad; Maillet, Philippe; Benais-Pont, Gaelle; Pardo, Bruno; Laitman, Yael; Friedman, Eitan; Velasco, Eladio A.; Duran, Mercedes; Miramar, Maria-Dolores; Rodriguez Valle, Ana; Calvo, Maria-Teresa; Vega, Ana; Blanco, Ana; Diez, Orland; Gutierrez-Enriquez, Sara; Balmana, Judith; Ramon y Cajal, Teresa; Alonso, Carmen; Baiget, Montserrat; Foulkes, William; Tischkowitz, Marc; Kyle, Rachel; Sabbaghian, Nelly; Ashton-Prolla, Patricia; Ewald, Ingrid P.; Rajkumar, Thangarajan; Mota-Vieira, Luisa; Giannini, Giuseppe; Gulino, Alberto; Achatz, Maria I.; Carraro, Dirce M.; de Paillerets, Brigitte Bressac; Remenieras, Audrey; Benson, Cindy; Casadei, Silvia; King, Mary-Claire; Teugels, Erik; Teixeira, Manuel R.

    2011-01-01

    The c.156_157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a to

  8. International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation

    DEFF Research Database (Denmark)

    Peixoto, Ana; Santos, Catarina; Pinheiro, Manuela;

    2011-01-01

    The c.156_157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a...

  9. 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

  10. Adherence to the breast cancer surveillance program for women at risk for familial breast and ovarian cancer versus overscreening: a monocenter study in Germany.

    Science.gov (United States)

    Vetter, Lisa; Keller, Monika; Bruckner, Thomas; Golatta, Michael; Eismann, Sabine; Evers, Christina; Dikow, Nicola; Sohn, Christof; Heil, Jörg; Schott, Sarah

    2016-04-01

    Breast cancer (BC) is the leading cancer among women worldwide and in 5-10 % of cases is of hereditary origin, mainly due to BRCA1/2 mutations. Therefore, the German Consortium for Familial Breast and Ovarian Cancer (HBOC) with its 15 specialized academic centers offers families at high risk for familial/hereditary cancer a multimodal breast cancer surveillance program (MBCS) with regular breast MRI, mammography, ultrasound, and palpation. So far, we know a lot about the psychological effects of genetic testing, but we know little about risk-correlated adherence to MBCS or prophylactic surgery over time. The aim of this study was to investigate counselees' adherence to recommendations for MBCS in order to adjust the care supply and define predictors for incompliance. All counselees, who attended HBOC consultation at the University Hospital Heidelberg between July 01, 2009 and July 01, 2011 were eligible to participate. A tripartite questionnaire containing sociodemographic information, psychological parameters, behavioral questions, and medical data collection from the German consortium were used. A high participation rate was achieved among the study population, with 72 % returning the questionnaire. This study showed a rate of 59 % of full-adherers to the MBCS. Significant predictors for partial or full adherence were having children (p = 0.0221), younger daughters (p = 0.01795), a higher awareness of the topic HBOC (p = 0.01795, p breast cancer risk (p breast cancer surveillance program for women at risk for familial breast and ovarian cancer versus overscreening-a monocenter study in Germany.

  11. Protecting Family Interests: An Interview Study with Foreign-Born Parents Struggling On in Childhood Cancer Care

    Directory of Open Access Journals (Sweden)

    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.

  12. Exome Sequencing in a Family with Luminal-Type Breast Cancer Underpinned by Variation in the Methylation Pathway

    Science.gov (United States)

    van der Merwe, Nicole; Peeters, Armand V.; Pienaar, Fredrieka M.; Bezuidenhout, Juanita; van Rensburg, Susan J.; Kotze, Maritha J.

    2017-01-01

    Panel-based next generation sequencing (NGS) is currently preferred over whole exome sequencing (WES) for diagnosis of familial breast cancer, due to interpretation challenges caused by variants of uncertain clinical significance (VUS). There is also no consensus on the selection criteria for WES. In this study, a pathology-supported genetic testing (PSGT) approach was used to select two BRCA1/2 mutation-negative breast cancer patients from the same family for WES. Homozygosity for the MTHFR 677 C>T mutation detected during this PSGT pre-screen step was considered insufficient to cause bilateral breast cancer in the index case and her daughter diagnosed with early-onset breast cancer ( 5%) in the folate pathway in all three affected family members is consistent with inheritance of the luminal-type breast cancer in the family. PSGT assisted with the decision to pursue extended genetic testing and facilitated clinical interpretation of WES aimed at reduction of recurrence risk. PMID:28241424

  13. 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...... proven noncarriers in 239 BRCA1 and BRCA2 families compared with birth-matched controls from the Danish Civil Registration System. Prospective analysis showed no significantly increased risk for breast cancer in noncarriers with a hazard ratio of 0.67 [95 % confidence interval (CI) 0.32-1.42, p = 0.......29] for all family members who tested negative and 0.87 (95 % CI 0.38-1.97, p = 0.73) for non-carries who were first-degree relatives of mutation carriers. Proven noncarriers from BRCA1 and BRCA2 families have no markedly increased risk for breast cancer compared to the general population, and our data do...

  14. 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

  15. Whole Genome Sequencing of High-Risk Families to Identify New Mutational Mechanisms of Breast Cancer Predisposition

    Science.gov (United States)

    2015-12-01

    Families to Identify New Mutational Mechanisms of Breast Cancer Predisposition 5b. GRANT NUMBER W81XWH-13-1-0336 5c. PROGRAM ELEMENT NUMBER 6...An integrative approach to predicting the functional effects of non-coding and coding sequence variation. Bioinformatics. 31:1536-1543. 14 Fu Y...Breast Cancer Predisposition PRINCIPAL INVESTIGATOR: Mary-Claire King, PhD CONTRACTING ORGANIZATION: University of Washington Seattle, WA, 98195

  16. Odin (ANKS1A is a Src family kinase target in colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    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.

  17. copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.

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    Kirsi M Kuusisto

    Full Text Available BACKGROUND: Inherited factors predisposing individuals to breast and ovarian cancer are largely unidentified in a majority of families with hereditary breast and ovarian cancer (HBOC. We aimed to identify germline copy number variations (CNVs contributing to HBOC susceptibility in the Finnish population. METHODS: A cohort of 84 HBOC individuals (negative for BRCA1/2-founder mutations and pre-screened for the most common breast cancer genes and 36 healthy controls were analysed with a genome-wide SNP array. CNV-affecting genes were further studied by Gene Ontology term enrichment, pathway analyses, and database searches to reveal genes with potential for breast and ovarian cancer predisposition. CNVs that were considered to be important were validated and genotyped in 20 additional HBOC individuals (6 CNVs and in additional healthy controls (5 CNVs by qPCR. RESULTS: An intronic deletion in the EPHA3 receptor tyrosine kinase was enriched in HBOC individuals (12 of 101, 11.9% compared with controls (27 of 432, 6.3% (OR = 1.96; P = 0.055. EPHA3 was identified in several enriched molecular functions including receptor activity. Both a novel intronic deletion in the CSMD1 tumor suppressor gene and a homozygous intergenic deletion at 5q15 were identified in 1 of 101 (1.0% HBOC individuals but were very rare (1 of 436, 0.2% and 1 of 899, 0.1%, respectively in healthy controls suggesting that these variants confer disease susceptibility. CONCLUSION: This study reveals new information regarding the germline CNVs that likely contribute to HBOC susceptibility in Finland. This information may be used to facilitate the genetic counselling of HBOC individuals but the preliminary results warrant additional studies of a larger study group.

  18. 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.

  19. 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.

  20. Role of KCNMA1 in breast cancer.

    Directory of Open Access Journals (Sweden)

    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.

  1. Health care restructuring and family physician care for those who died of cancer

    Directory of Open Access Journals (Sweden)

    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

  2. MiRNA Profiles in Lymphoblastoid Cell Lines of Finnish Prostate Cancer Families.

    Directory of Open Access Journals (Sweden)

    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

  3. Assessment of a six gene panel for the molecular detection of circulating tumor cells in the blood of female cancer patients

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    Horvat Reinhard

    2010-12-01

    Full Text Available Abstract Background The presence of circulating tumor cells (CTC in the peripheral blood of cancer patients has been described for various solid tumors and their clinical relevance has been shown. CTC detection based on the analysis of epithelial antigens might be hampered by the genetic heterogeneity of the primary tumor and loss of epithelial antigens. Therefore, we aimed to identify new gene markers for the PCR-based detection of CTC in female cancer patients. Methods Gene expression of 38 cancer cell lines (breast, ovarian, cervical and endometrial and of 10 peripheral blood mononuclear cell (PBMC samples from healthy female donors was measured using microarray technology (Applied Biosystems. Differentially expressed genes were identified using the maxT test and the 50% one-sided trimmed maxT-test. Confirmatory RT-qPCR was performed for 380 gene targets using the AB TaqMan® Low Density Arrays. Then, 93 gene targets were analyzed using the same RT-qPCR platform in tumor tissues of 126 patients with primary breast, ovarian or endometrial cancer. Finally, blood samples from 26 healthy women and from 125 patients (primary breast, ovarian, cervical, or endometrial cancer, and advanced breast cancer were analyzed following OncoQuick enrichment and RNA pre-amplification. Likewise, hMAM and EpCAM gene expression was analyzed in the blood of breast and ovarian cancer patients. For each gene, a cut-off threshold value was set at three standard deviations from the mean expression level of the healthy controls to identify potential markers for CTC detection. Results Six genes were over-expressed in blood samples from 81% of patients with advanced and 29% of patients with primary breast cancer. EpCAM gene expression was detected in 19% and 5% of patients, respectively, whereas hMAM gene expression was observed in the advanced group (39% only. Multimarker analysis using the new six gene panel positively identified 44% of the cervical, 64% of the

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. MR-guided intervention in women with a family history of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Viehweg, P. [Institute of Diagnostic Radiology, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden (Germany)]. E-mail: Petra.Viehweg@uniklinikum-dresden.de; Bernerth, T. [Department of Diagnostic Radiology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 16, 06097 Halle (Germany); Kiechle, M. [Department of Obstetrics and Gynaecology, Technical University Munich, Ismaninger Strasse 22, 81675 Munich (Germany); Buchmann, J. [Department of Pathology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 14, 06097 Halle (Germany); Heinig, A. [Department of Diagnostic Radiology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 16, 06097 Halle (Germany); Koelbl, H. [Department of Obstetrics and Gynaecology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 24, 06097 Halle (Germany); Laniado, M. [Institute of Diagnostic Radiology, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden (Germany); Heywang-Koebrunner, S.H. [Department of Diagnostic Radiology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 16, 06097 Halle (Germany); Department of Diagnostic Radiology, Technical University Munich, Ismaninger Strasse 19, 81675 Munich (Germany)

    2006-01-15

    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.

  9. Expression of p53 family genes in urinary bladder cancer: correlation with disease aggressiveness and recurrence.

    Science.gov (United States)

    Papadogianni, Danae; Soulitzis, Nikolaos; Delakas, Demetrios; Spandidos, Demetrios A

    2014-03-01

    p53 is a tumour suppressor gene with an established role in the majority of human neoplasias. Its homologues-p63 and p73-cannot be classified as tumour suppressors, since they encode isoforms with oncogenic properties as well. p63 plays a crucial role in epithelial cell differentiation and p73 is essential for neuronal cell development. The p63 and p73 expressions have been investigated in a variety of human tumours including bladder carcinomas; yet, this is the first study to simultaneously analyse the transcriptional levels of all p53 family members in bladder cancer. Using quantitative real-time polymerase chain reaction, we measured the mRNA expression of p53, p63 and p73 in 30 bladder tumours, each paired with adjacent normal tissue. All three studied genes were up-regulated in malignant specimens, p53 by 1.9-fold, p63 by threefold and p73 by twofold, respectively. Further analysis suggested that p63 and p73 act independently of p53 in the malignant bladder epithelium. Statistical analysis revealed that p63 overexpression was more frequent in recurrent bladder tumours (p = 0.045) and in older patients (p = 0.022). Papillary tumours also exhibited abnormal p63 expression (p = 0.026). Finally, p73 was up-regulated in Grade III one-site tumours (p = 0.040). Our results indicate that all p53 family members are abnormally expressed in bladder cancer but do not act synergistically. High levels of p63 correlate with non-muscle invasive tumours with frequent relapses, whereas p73 overexpression is associated with a more aggressive tumour phenotype.

  10. An overview of the GAGE cancer/testis antigen family with the inclusion of newly identified members

    DEFF Research Database (Denmark)

    Gjerstorff, M F; Ditzel, H J

    2008-01-01

    GAGE cancer/testis antigens are frequently expressed in many different types of cancer, whereas their expression in normal tissues is limited to the germ cells of the immune-privileged organs, testis and ovary. Thus, GAGE proteins may be attractive candidates for immunotherapy of cancer....... This review describes the structure and phylogeny of the GAGE family members and presents a revised nomenclature, which will enable a more clear distinction of genes and gene products. The GAGE gene locus at chromosome X p11.23 consists of at least 16 genes, each of which is located in one of an equal number...... cell biology. When expressed in tumor cells, GAGE proteins can elicit both cellular and humoral immune responses, indicating that they are appropriate targets for cancer immunotherapy. The potential use of GAGE proteins in cancer immunotherapy, including possible limitations, is also discussed....

  11. Factors associated with quality of life of outpatients with breast cancer and gynecologic cancers and their family caregivers: a controlled study

    Directory of Open Access Journals (Sweden)

    Hamad Hussein MA

    2007-06-01

    Full Text Available Abstract Background Quality of life (QOL issues are of interest in cancer because effective methods of treatment and detection have led to an increase in the number of long-term survivors. The objectives of the study were: to assess the subjective QOL of stable Sudanese women cancer outpatients and their family caregivers, using the WHO 26-item QOL Instrument; compare with matched general population groups, as well as diabetic and psychiatric patient groups; examine patient-caregiver concordance in ratings; and assess the variables associated with their QOL, with a view to identifying factors that can enhance quality of care. Methods Responses of oncology outpatients with breast cancer (117, cervical cancer (46 and ovarian cancer (18 (aged 44.6, SD 11.5 were compared with those of their family caregivers and matched general population groups. Data were analyzed by univariate and multivariate statistics. Results The cancer groups had similar QOL domain scores, which were significantly lower than those of their caregivers, but higher than the control group as well as those of psychiatric and diabetic patients studied previously. Patients who were married, with higher education, better employment, and with longer duration of illness had higher QOL. Patients on radiotherapy and their caregivers had higher QOL scores. Correlations between patient's ratings and caregiver impression of patient's QOL were high. Caregiver impression was a significant predictor of patient's and caregiver's QOL. Other predictors for the patient were: currently feeling sick and duration of illness; for the caregiver: feeling sick, relationship to patient, and age. Conclusion Cancer patients in stable condition and with psychosocial support can hope to enjoy good QOL with treatment. The findings constitute an evidence base for the country's cancer care program, to boost national health education about prognosis in cancer. Families living with women cancer patients are

  12. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  13. Factors associated with prostate cancer patients' and their spouses' satisfaction with a family-based intervention.

    Science.gov (United States)

    Harden, Janet; Falahee, Margaret; Bickes, Joan; Schafenacker, Ann; Walker, Julie; Mood, Darlene; Northouse, Laurel

    2009-01-01

    Only a few programs are designed to help couples cope with the effects of prostate cancer, and typically, only their intervention outcomes are reported. The purpose of this study was to assess prostate cancer patients' and their spouses' satisfaction with an efficacious supportive-educative, family-based intervention, and factors associated with their satisfaction. We assessed the relationship of overall satisfaction with the intervention to (1) the patients' and spouses' appraisal and the resource and quality-of-life baseline scores and (2) changes in those scores after completing the intervention. Results showed that participants were very satisfied with the program. Patients who had higher scores on baseline measures, indicating more positive appraisal of their illness, better use of resources (eg, coping, self-efficacy), and higher overall quality of life, reported more satisfaction with the intervention. For spouses, few baseline measures were related to their satisfaction; however, spouses who reported positive changes after intervention (less negative appraisal and uncertainty, better communication) reported higher satisfaction with the program. Although satisfied with the program, factors associated with patients' and spouses' satisfaction differed. To translate effective interventions to clinical practice settings, it is important to assess participants' satisfaction with program content and delivery, as well as program outcomes.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Impact of Genetic Counseling in Women with a Family History of Breast Cancer in Italy.

    Science.gov (United States)

    Godino, Lea; Razzaboni, Elisabetta; Bianconi, Margherita; Turchetti, Daniela

    2016-04-01

    As the impact of breast cancer (BC) risk assessment in asymptomatic women with a family history of BC had never been explored in Italy, we performed a study on a retrospective series of women who had undergone BC risk assessment. To this aim, a semi-structured telephone interview was administered to 82 women. Most participants considered the information received as clear (96.2 %) and helpful (76.8 %). Thirty-eight (46.3 %) stated that their perceived risk of BC had changed after the counseling: for 40.2 % it had decreased, for 6.1 % increased; however, women highly overestimating their risk at the baseline (≥ 4-fold) failed to show improvements in risk perception accuracy. Sixty-six women (80.5 %) stated they had followed the recommended surveillance, while 19.5 % had not, mainly due to difficulties in arranging examinations. Most women (89.0 %) had shared the information with their relatives, with 57.3 % reporting other family members had undertaken the recommended surveillance. BC risk assessment was associated with high rates of satisfaction and had a favorable impact on risk perception in a subgroup of women. The impact on surveillance adhesion extended to relatives. Organized programs for identification and surveillance may help identify a larger fraction of at-risk women and overcome the reported difficulties in arranging surveillance.

  19. The transition experience of rural older persons with advanced cancer and their families: a grounded theory study

    Directory of Open Access Journals (Sweden)

    Berry Patricia H

    2010-04-01

    Full Text Available Abstract Background Transitions often occur suddenly and can be traumatic to both patients with advanced disease and their families. The purpose of this study was to explore the transition experience of older rural persons with advanced cancer and their families from the perspective of palliative home care patients, bereaved family caregivers, and health care professionals. The specific aims were to: (1 describe the experience of significant transitions experienced by older rural persons who were receiving palliative home care and their families and (2 develop a substantive theory of transitions in this population. Methods Using a grounded theory approach, 27 open-ended individual audio-taped interviews were conducted with six older rural persons with advanced cancer and 10 bereaved family caregivers. Four focus group interviews were conducted with 12 palliative care health care professionals. All interviews were transcribed verbatim, coded, and analyzed using Charmaz's constructivist grounded theory approach. Results Within a rural context of isolation, lack of information and limited accessibility to services, and values of individuality and community connectedness, older rural palliative patients and their families experienced multiple complex transitions in environment, roles/relationships, activities of daily living, and physical and mental health. Transitions disrupted the lives of palliative patients and their caregivers, resulting in distress and uncertainty. Rural palliative patients and their families adapted to transitions through the processes of "Navigating Unknown Waters". This tentative theory includes processes of coming to terms with their situation, connecting, and redefining normal. Timely communication, provision of information and support networks facilitated the processes. Conclusion The emerging theory provides a foundation for future research. Significant transitions identified in this study may serve as a focus for

  20. 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.

  1. 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.

  2. 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.

  3. A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

    NARCIS (Netherlands)

    de Bock, Geertruida H.; Jacobi, Catharina E.; Seynaeve, Caroline; Krol-Warmerdam, Elly M. M.; Blom, Jannet; van Asperen, Christi J.; Cornelisse, Cees J.; Klijn, Jan G. M.; Devilee, Peter; Tollenaar, Rob A. E. M.; Brekelmans, Cecile T. M.; van Houwelingen, Johannes C.

    2008-01-01

    Background: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data

  4. Selection of Aptamers for CED-9/Bcl-2 Family Cell Death Regulations and Their Application in Study of Apoptosis Regulation and Drug Design for Breast Cancer

    Science.gov (United States)

    2005-07-01

    Apoptosis Regulation and Drug Design for Breast Cancer PRINCIPAL INVESTIGATOR: Ding Xue, Ph.D. Chonglin Yang, Ph.D. Nathan Camp CONTRACTING ORGANIZATION...Aptamers for CED-9/Bcl-2 Family Cell Death Regulations and Their Application in Study of Apoptosis Regulation and Drug Design for Breast Cancer 5b. GRANT...aptamers for CED-9/Bcl-2 family cell death regulators and their application in study of apoptosis regulation and drug design for breast cancer. The 4th Era

  5. How do women at increased, but unexplained, familial risk of breast cancer perceive and manage their risk? A qualitative interview study

    Directory of Open Access Journals (Sweden)

    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.

  6. Perceived risk, anxiety, mammogram uptake and breast self examination of women with a family history of breast cancer: The role of knowing to be at increased risk

    NARCIS (Netherlands)

    Drossaert, C.H.C.; Boer, H.; Seydel, E.R.

    1996-01-01

    Since women with a first-degree relative with breast cancer are at increased risk for breast cancer, it is of special importance that they adhere to early detection programs. In this study, women with (389) and without (3295) a family history of breast cancer were compared with respect to risk perce

  7. 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.

  8. Family doctor-driven follow-up for adult childhood cancer survivors supported by a web-based survivor care plan

    NARCIS (Netherlands)

    Blaauwbroek, R.; Barf, H. A.; Groenier, K. H.; Kremer, L. C.; van der Meer, K.; Tissing, W. J. E.; Postma, A.

    2012-01-01

    To facilitate family doctor-driven follow-up for adult childhood cancer survivors, we developed a survivor care plan (SCP) for adult survivors and their family doctors. The SCP was accessible for survivors and their family doctors on a secure website and as a printed booklet. It included data on dia

  9. Predictors of Family Conflict at the End of Life: The Experience of Spouses and Adult Children of Persons with Lung Cancer

    Science.gov (United States)

    Kramer, Betty J.; Kavanaugh, Melinda; Trentham-Dietz, Amy; Walsh, Matthew; Yonker, James A.

    2010-01-01

    Purpose: Guided by an explanatory matrix of family conflict at the end of life, the purpose of this article was to examine the correlates and predictors of family conflict reported by 155 spouses and adult children of persons with lung cancer. Design and Methods: A cross-sectional statewide survey of family members of persons who died from lung…

  10. 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

    Directory of Open Access Journals (Sweden)

    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

  11. 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

  12. The HABP2 G534E Variant Is an Unlikely Cause of Familial Nonmedullary Thyroid Cancer

    Science.gov (United States)

    Sahasrabudhe, Ruta; Stultz, Jacob; Williamson, John; Lott, Paul; Estrada, Ana; Bohorquez, Mabel; Palles, Claire; Polanco-Echeverry, Guadalupe; Jaeger, Emma; Martin, Lynn; Echeverry, Maria Magdalena; Tomlinson, Ian

    2016-01-01

    Context: A recent study reported the nonsynonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial nonmedullary thyroid cancer (NMTC). Objective: The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multicenter population-based study of NMTC cases from the British Isles. Design and Setting: A case-control analysis of rs7080536 genotypes was performed using 2105 TCUKIN cases and 5172 UK controls. Participants: Cases comprised 2105 NMTC cases. Patient subgroups with papillary (n = 1056), follicular (n = 691), and Hürthle cell (n = 86) thyroid cancer cases were studied separately. Controls comprised 5172 individuals from the 1958 Birth Cohort and the National Blood Donor Service study. The controls had previously been genotyped using genome-wide single nucleotide polymorphism arrays by the Wellcome Trust Case Control Consortium study. Outcome Measures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression. Results: The frequency of the HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (odds ratio [OR] = 0.896; 95% confidence interval, 0.746–1.071; P = .233). We also failed to detect an association between the HABP2 G534E and cases with papillary (1056 cases; G534E frequency = 3.5%; OR = 0.74; P = .017), follicular (691 cases; G534E frequency = 4.7%; OR = 1.00; P = 1.000), or Hürthle cell (86 cases; G534E frequency = 6.3%; OR = 1.40; P = .279) histology. Conclusions: We found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC, and additional data are required before using this variant in NMTC risk assessment. PMID:26691890

  13. A Tailored Web-Based Psycho-Educational Intervention for Cancer Patients and Their Family Caregivers

    Science.gov (United States)

    Northouse, Laurel; Schafenacker, Ann; Barr, Kathryn L.C.; Katapodi, Maria; Yoon, Hyojin; Brittain, Kelly; Song, Lixin; Ronis, David L.; An, Larry

    2014-01-01

    Background Most programs addressing psychosocial concerns of cancer survivors are in-person programs that are expensive to deliver, have limited availability, and seldom deal with caregivers’ concerns. Objective This study examined the feasibility of translating an efficacious nurse-delivered program (FOCUS Program) for patients and their caregivers to a tailored, dyadic web-based format. Specific aims were to: (i) test the preliminary effects of the web-based intervention on patient and caregiver outcomes, (ii) examine participants’ program satisfaction, and (iii) determine the feasibility of using a web-based delivery format. Intervention/Methods A Phase II feasibility study was conducted with cancer patients (lung, breast, colorectal, prostate) and their family caregivers (N=38 dyads). The web-based intervention provided information and support tailored to the unique characteristics of each patient, caregiver, and their dyadic relationship. Primary outcomes were emotional distress and quality of life (QOL). Secondary outcomes were benefits of illness/caregiving, communication, support, and self-efficacy. Analyses included descriptive statistics and repeated measures ANOVA. Results Dyads had a significant decrease in emotional distress, increase in QOL, and perceived more benefits of illness/caregiving. Caregivers also had significant improvement in self-efficacy. There were no changes in communication. Participants were satisfied with program usability, but recommended additional content. Conclusions It was possible to translate a clinician-delivered program to a web-based format that was easy to use and had positive effects on dyadic outcomes. Implications for Practice The web-based program is a promising way to provide psychosocial care to more patients and caregivers using fewer personnel. It needs further testing in a larger RCT. PMID:24945270

  14. 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

  15. 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.

  16. The inhibitor of growth (ING) gene family: potential role in cancer therapy.

    Science.gov (United States)

    Gunduz, Mehmet; Gunduz, Esra; Rivera, Rosario S; Nagatsuka, Hitoshi

    2008-06-01

    The discovery of ING1 gene paved the way to the identification of other ING members (ING2-5) and their isoforms associated with cell cycle, apoptosis and senescence. The ING family has been an emerging putative tumor suppressor gene (TSG) in which the major mechanism is through interaction with the determinants of chromatin function and gene-specific transcription factors. The regulatory mechanism highly involves the conserved plant homeodomain (PHD), which binds to histones in a methylation-sensitive manner, suggesting that ING proteins may contribute to the maintenance of the epigenetic code. Furthermore, ING family members contain nuclear localization signals and N-terminal sequences important in the interaction with histone acetyltransferase (HAT) and histone deacetyltransferase (HDAC) that regulate gene promoter activity within chromatin. Although ING proteins have the same PHD motif, the variation in the N-terminal dictates the differences in tumor the suppressive ability of ING in various tumors. Inactivation of the normal function is achieved through allelic loss of genomic regions containing the ING gene, alteration in the ING promoter region, variation of mRNA splicing efficacy or reduced mRNA stability. It is most probably the apparent combination of these aberrant mechanisms that resulted in reduced availability of functional ING protein. In cancer cells, ING transcript levels are often suppressed but the genes are rarely mutated. The mechanism of suppression of ING expression may have to do with the abnormally high methylation levels of the ING gene promoter, which have been correlated with low transcript levels. Emerging evidence on the function of ING and related regulatory mechanisms strongly points to ING as a candidate TSG and therefore a potential target in the molecular therapy of some types of tumor.

  17. Telomere Length Polymorphisms: A Potential Factor Underlying Increased Risk of Prostate Cancer in African American Men and Familial Prostate Cancer

    Science.gov (United States)

    2008-12-01

    markers to allow specific identification of prostate cancer cells in urine cytology specimens. 10 Role: PI Patrick C. Walsh Prostate Cancer Research...Detection of Prostate Cancer in Urine by Multiplex Immunofluorescence and Telomere FISH – Guiding Clinical Decisions Following Negative Prostate

  18. Offline Social Relationships and Online Cancer Communication: Effects of Social and Family Support on Online Social Network Building.

    Science.gov (United States)

    Namkoong, Kang; Shah, Dhavan V; Gustafson, David H

    2016-11-08

    This study investigates how social support and family relationship perceptions influence breast cancer patients' online communication networks in a computer-mediated social support (CMSS) group. To examine social interactions in the CMSS group, we identified two types of online social networks: open and targeted communication networks. The open communication network reflects group communication behaviors (i.e., one-to-many or "broadcast" communication) in which the intended audience is not specified; in contrast, the targeted communication network reflects interpersonal discourses (i.e., one-to-one or directed communication) in which the audience for the message is specified. The communication networks were constructed by tracking CMSS group usage data of 237 breast cancer patients who participated in one of two National Cancer Institute-funded randomized clinical trials. Eligible subjects were within 2 months of a diagnosis of primary breast cancer or recurrence at the time of recruitment. Findings reveal that breast cancer patients who perceived less availability of offline social support had a larger social network size in the open communication network. In contrast, those who perceived less family cohesion had a larger targeted communication network in the CMSS group, meaning they were inclined to use the CMSS group for developing interpersonal relationships.

  19. A Thai family with hereditary pancreatitis and increased cancer risk due to a mutation in PRSS1 gene

    Institute of Scientific and Technical Information of China (English)

    Theeraphong Pho-Iam; Wanna Thongnoppakhun; Pa-Thai Yenchitsomanus; Chanin Limwongse

    2005-01-01

    AIM: To investigate mutation of serine protease 1-cationic trypsinogen (CT, PRSS1) gene in members of a Thai family with hereditary pancreatitis and pancreatic cancer.METHODS: Polymerase chain reaction and direct sequencing were performed to analyze the PRSS1 gene in two members of the family affected by pancreatitis.Allele specific amplification (ASA) method was then developed to detect the mutation of the PRSS1 gene in all available members of the family and normal control subjects.RESULTS: A cytosine (C) to thymine (T) mutation at position 2441 (g.2441C>T) of the PRSS1 gene, which results in a substitution of arginine by cysteine at position 116 (R116C) of CT, was identified by direct sequencing in both clinically affected members of the family but was not found in the unaffected member. This mutation, which might be arising from deamination of methylated cytosine in CpG dinucleotide of codon 116 (CGT>FGT), was also detected by the ASA method in the two affected members and a proband's brother but was not observed in unaffected members and 54 normal control subjects.CONCLUSION: Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1gene.

  20. Phenocopy breast cancer rates in Israeli BRCA1 BRCA2 mutation carrier families: is the risk increased in non-carriers?

    Science.gov (United States)

    Bernholtz, Shiri; Laitman, Yael; Kaufman, Bella; Shimon-Paluch, Shnai; Friedman, Eitan

    2012-04-01

    BRCA1 and BRCA2 mutation carriers have an increased risk for developing breast (and ovarian) cancer. Non-carriers from within such families (=true negatives) are counseled that their risk for developing breast cancer is similar to that of the average-risk population. Breast cancer diagnosed in a non-carrier from a family with a known mutation is coined phenocopy. The rate of breast cancer phenocopy and the risk for breast cancer in true negatives are unsettled. The rate of phenocopy breast cancer was assessed in non-carriers from Jewish families with a BRCA1 or BRCA2 mutation, identified at the Sheba medical center. Analysis was performed by t test for comparison of mean age at counseling or breast cancer diagnosis, and by calculating a standardized incidence ratio (SIR). Overall, 1318 females from 884 mutation carrying families (620 with BRCA1 264 with BRCA2 mutations) were genotyped, of whom 307 women from 245 families were assigned a true negative status (mean age at counseling 43.01 ± 13.03 years (range 19.7-92.8 years). Of these true negatives, 20 women (6.51-2.26% of families) developed breast cancer at a mean age of 54.1 ± 12.9 years (range 48.1 -60.1 years). The SIR for breast cancer in true negatives was not significantly different than the expected in the average-risk Israeli population [observed 20-expected 23.8 cases SIR = 0.84, 95% CI (0.51, 1.30)]. The rate of phenocopy breast cancer in non-carriers from Israeli BRCA1 BRCA2 mutation carrier families is 2.26% with no increased breast cancer risk over the average-risk population.

  1. 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; David A Norris; 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...

  2. Expression of the Bcl-2 family genes and complexes involved in the mitochondrial transport in prostate cancer cells.

    Science.gov (United States)

    Asmarinah, Asmarinah; Paradowska-Dogan, Agnieszka; Kodariah, Ria; Tanuhardja, Budiana; Waliszewski, Przemyslaw; Mochtar, Chaidir Arif; Weidner, Wolfgang; Hinsch, Elvira

    2014-10-01

    Alteration of molecular pathways triggering apoptosis gives raise to various pathological tissue processes, such as tumorigenesis. The mitochondrial pathway is regulated by both the genes of the Bcl-2 family and the genes encoding mitochondrial transport molecules. Those proteins allow a release of cyctochrome c through the outer mitochondrial membrane. This release activates the caspase cascade resulting in death of cells. There are at least two main transport systems associated with the family of Bcl-2 proteins that are involved in transport of molecules through the outer mitochondrial membrane, i.e., the voltage dependent anion channels (VDACs) and translocases of the outer mitochondrial membrane proteins (TOMs). We investigated the expression of genes of the Bcl-2 family, i.e., pro-apoptotic Bak and Bid, and anti-apoptotic Bcl-2; VDAC gene, i.e., VDAC1, VDAC2 and VDAC3; and TOMM genes, i.e., TOMM20, TOMM22 and TOMM40. This study was performed at the mRNA and the protein level. Fourteen paraffin embedded prostate cancer tissues and five normal prostate tissues were analyzed by the quantitative PCR array and immunohistochemistry. We found a significant increase in both mRNA expression of the anti-apoptotic Bcl-2 gene and VDAC1 gene in prostate cancer tissue in comparison with their normal counterparts. Translation of the anti-apoptotic Bcl-2 and VDAC1 genes in prostate cancer tissue was slightly increased. We observed no significant differences in the mRNA expression of the pro-apoptotic Bak and Bid genes, VDAC2 or VDAC3 genes or the three TOMM genes in these tissues. The pro-apoptotic Bax protein was downtranslated significantly in secretory cells of prostate cancer as compared to normal prostate. We suggest that this protein is a good candidate as biomarker for prostate cancer.

  3. The human TLR innate immune gene family is differentially influenced by DNA stress and p53 status in cancer cells.

    Science.gov (United States)

    Shatz, Maria; Menendez, Daniel; Resnick, Michael A

    2012-08-15

    The transcription factor p53 regulates genes associated with a wide range of functions, including the Toll-like receptor (TLR) set of innate immunity genes, suggesting that p53 also modulates the human immune response. The TLR family comprises membrane glycoproteins that recognize pathogen-associated molecular patterns (PAMP) and mediate innate immune responses, and TLR agonists are being used as adjuvants in cancer treatments. Here, we show that doxorubicin, 5-fluorouracil, and UV and ionizing radiation elicit changes in TLR expression that are cell line- and damage-specific. Specifically, treatment-induced expression changes led to increased downstream cytokine expression in response to ligand stimulation. The effect of DNA stressors on TLR expression was mainly mediated by p53, and several p53 cancer-associated mutants dramatically altered the pattern of TLR gene expression. In all cell lines tested, TLR3 induction was p53-dependent, whereas induction of TLR9, the most stress-responsive family member, was less dependent on status of p53. In addition, each of the 10 members of the innate immune TLR gene family tested was differentially inducible. Our findings therefore show that the matrix of p53 status, chromosome stress, and responsiveness of individual TLRs should be considered in TLR-based cancer therapies.

  4. Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development

    Directory of Open Access Journals (Sweden)

    Angelica Judith Granados-López

    2017-02-01

    Full Text Available Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches.

  5. Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development

    Science.gov (United States)

    Granados-López, Angelica Judith; Ruiz-Carrillo, José Luis; Servín-González, Luis Steven; Martínez-Rodríguez, José Luis; Reyes-Estrada, Claudia Araceli; Gutiérrez-Hernández, Rosalinda; López, Jesús Adrián

    2017-01-01

    Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches. PMID:28216603

  6. 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.)

  7. 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....

  8. 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...... 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...

  9. 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.

  10. Trajectories of fatigue in family caregivers of patients undergoing radiation therapy for prostate cancer.

    Science.gov (United States)

    Fletcher, Barbara A Swore; Schumacher, Karen L; Dodd, Marylin; Paul, Steven M; Cooper, Bruce A; Lee, Kathryn; West, Claudia; Aouizerat, Bradley E; Swift, Patrick S; Wara, William; Miaskowski, Christine

    2009-04-01

    Predictors of and trajectories for evening and morning fatigue were evaluated in family caregivers of oncology patients using hierarchical linear modeling. Evening fatigue trajectory fit a quadratic model. Predictors included baseline sleep disturbances in family caregivers and baseline evening fatigue in patients. Morning fatigue trajectory fit a linear model. Predictors were baseline trait anxiety, levels of perceived family support, and baseline morning fatigue in patients. Findings suggest considerable inter-individual variability in the trajectories of evening and morning fatigue. Evaluating family caregivers for sleep disturbance, anxiety, and poor family support, as well as high levels of patient fatigue, could identify those family caregivers at highest risk for sustained fatigue trajectories.

  11. Cancer Research Repository for Individuals With Cancer Diagnosis, High Risk Individuals, and Individuals With No History of Cancer (Control)

    Science.gov (United States)

    2016-11-14

    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; Breastcancer; Leukemia; Melanoma; Sarcoma; Unknown Primary Tumor; Multiple Myeloma; Ovarian Cancer; Endometrial Cancer; Vaginal Cancer

  12. 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

  13. CD44 family proteins in gastric cancer: a meta-analysis and narrative review.

    Science.gov (United States)

    Wu, Ying; Li, Zhi; Zhang, Chenlu; Yu, Kai; Teng, Zan; Zheng, Guoliang; Wang, Shuang; Liu, Yunpeng; Cui, Lei; Yu, Xiaosong

    2015-01-01

    With a meta-analysis and narrative review, we evaluated the clinical and prognostic role of all CD44 family proteins in gastric cancer (GC). Literatures published up to August 2014 were searched on PubMed. Among the 37 eligible studies (6606 patients), 34 were included in meta-analysis, and 10 were subjected to narrative review. With meta-analysis, standard CD44 (CD44s) was demonstrated to predict reduced overall survival (OS) (HR = 1.93, 95% CI: 1.58-2.34, PHR = 0.0222) and disease free survival (HR = 3.13, 95% CI: 1.02-9.68, PHR = 0.0469), advanced N-stage (RR = 1.12, 95% CI: 1.04-1.21, PRR = 0.0019), and distant metastasis (RR = 2.14, 95% CI: 1.46-3.14, PRR PRR = 0.0240), M-stage (RR = 2.54, 95% CI: 1.08-6.00, PRR = 0.0333), TNM-stage (RR = 1.72, 95% CI: 1.18-2.50, PRR = 0.0045), Lauren type (RR = 0.67, 95% CI: 0.50-0.91, PRR = 0.0106), lymphatic invasion (RR = 1.13, 95% CI: 1.04-1.23, PRR = 0.0057), and liver metastasis (RR = 3.20, 95% CI: 1.94-5.27, PRR < 0.0001) of the disease. Moreover, a narrative review was performed for CD44 isoforms, such as v3, v5, v7, v8-10, and v9, in GC. In conclusion, CD44s and CD44v6 as evaluated by immunohistochemistry, respectively, predicts the prognosis and disease severity of GC.

  14. 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,…

  15. Identification of cancer predisposition variants in apparently healthy individuals using a next-generation sequencing-based family genomics approach.

    Science.gov (United States)

    Karageorgos, Ioannis; Mizzi, Clint; Giannopoulou, Efstathia; Pavlidis, Cristiana; Peters, Brock A; Zagoriti, Zoi; Stenson, Peter D; Mitropoulos, Konstantinos; Borg, Joseph; Kalofonos, Haralabos P; Drmanac, Radoje; Stubbs, Andrew; van der Spek, Peter; Cooper, David N; Katsila, Theodora; Patrinos, George P

    2015-06-20

    Cancer, like many common disorders, has a complex etiology, often with a strong genetic component and with multiple environmental factors contributing to susceptibility. A considerable number of genomic variants have been previously reported to be causative of, or associated with, an increased risk for various types of cancer. Here, we adopted a next-generation sequencing approach in 11 members of two families of Greek descent to identify all genomic variants with the potential to predispose family members to cancer. Cross-comparison with data from the Human Gene Mutation Database identified a total of 571 variants, from which 47 % were disease-associated polymorphisms, 26 % disease-associated polymorphisms with additional supporting functional evidence, 19 % functional polymorphisms with in vitro/laboratory or in vivo supporting evidence but no known disease association, 4 % putative disease-causing mutations but with some residual doubt as to their pathological significance, and 3 % disease-causing mutations. Subsequent analysis, focused on the latter variant class most likely to be involved in cancer predisposition, revealed two variants of prime interest, namely MSH2 c.2732T>A (p.L911R) and BRCA1 c.2955delC, the first of which is novel. KMT2D c.13895delC and c.1940C>A variants are additionally reported as incidental findings. The next-generation sequencing-based family genomics approach described herein has the potential to be applied to other types of complex genetic disorder in order to identify variants of potential pathological significance.

  16. 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

  17. 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

    NARCIS (Netherlands)

    Saadatmand, Sepideh; Rutgers, Emiel J. T.; Tollenaar, Rob A. E. M.; Zonderland, Hermien M.; Ausems, Margreet G. E. M.; Keymeulen, Kristien B. M. I.; Schlooz-Vries, Margreet S.; Koppert, Linetta B.; Heijnsdijk, Eveline A. M.; Seynaeve, Caroline; Verhoef, Cees; Oosterwijk, Jan C.; Obdeijn, Inge-Marie; de Koning, Harry J.; Tilanus-Linthorst, Madeleine M. A.

    2012-01-01

    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 sensitivit

  18. MSH6 Mutations are Frequent in Hereditary Nonpolyposis Colorectal Cancer Families With Normal pMSH6 Expression as Detected by Immunohistochemistry

    DEFF Research Database (Denmark)

    Okkels, Henrik; Larsen, K.L.; Thorlacius-Ussing, O.;

    2012-01-01

    INTRODUCTION:: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition accounting for 2% to 4% of all colorectal cancer cases worldwide. Families with germ line mutations in 1 of 6 mismatch repair genes are known as Lynch syndrome families. The largest number...... of mutations has been detected in the mismatch repair genes MLH1 and MSH2, but several mutations in MSH6 have also been demonstrated. AIM:: Whether HNPCC families are screened for mutations in mismatch repair genes often relies on their immunohistochemical profile. The aim of the present study was to evaluate...... this approach in Lynch families carrying mutations in MSH6. MATERIALS AND METHODS:: Results of the screening of the MSH6 gene in HNPCC families were compared with those obtained on immunohistochemical protein analysis. RESULTS:: In 56 (7%) of 815 families, at least 1 MSH6 mutation, 23 definitively pathogenic...

  19. Analysis of BRCA1 and BRCA2 mutations in Brazilian breast cancer patients with positive family history

    Directory of Open Access Journals (Sweden)

    Rozany Mucha Dufloth

    Full Text Available CONTEXT AND OBJECTIVE: BRCA1 and BRCA2 are the two principal hereditary breast cancer susceptibility genes, and the prevalence of their mutations among Brazilian women is unknown. The objective was to detect BRCA1 and BRCA2 mutations in Brazilian patients with breast cancer, so as to establish genetic profiles. DESIGN AND SETTING: Cross-sectional study, in Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas, Brazil, and Institute of Pathology and Molecular Immunology, University of Porto, Portugal. METHODS: Thirty-one breast cancer patients with positive family history (criteria from the Breast Cancer Linkage Consortium were studied, and genomic DNA was extracted from peripheral blood. Single-strand conformation polymorphism was used for the analysis of exons 2, 3, 5, and 20 of BRCA1. Cases showing PCR products with abnormal bands were sequenced. Exon 11 of BRCA1 and exons 10 and 11 of BRCA2 were directly sequenced in both directions. RESULTS: Four mutations were detected: one in BRCA1 and three in BRCA2. The BRCA1 mutation is a frameshift located at codon 1756 of exon 20: 5382 ins C. Two BRCA2 mutations were nonsense mutations located at exon 11: S2219X and the other was an unclassified variant located at exon 11: C1290Y. CONCLUSION: The BRCA1 or BRCA2 mutation prevalence found among women with breast cancer and such family history was 13% (4/31. Larger studies are needed to establish the significance of BRCA mutations among Brazilian women and the prevalence of specific mutations.

  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. Evaluation of the Relationship Between Family History of Breast Cancer and Risk Perception and Impacts on Repetition of Mammography.

    Science.gov (United States)

    Khoshravesh, Sahar; Taymoori, Parvaneh; Roshani, Daem

    2016-01-01

    Since the mean age of breast cancer in women living in developing countries, compared with those in developed countries, is lower by about 10 years, repetition of mammography can play an important role in reducing morbidity and mortality. Hence, this study aimed to investigate the relationship between family history of breast cancer and risk perception and its impact on repetition of mammography. In this cross-sectional study, 1,507 women aged 50 years and older, referred to the mammography center of Regions 1 and 6 in Tehran, Iran, were enrolled. Data were collected using a self-report questionnaire and analyzed using SPSS and LISREL. According to our findings, knowledge about the time interval of mammography was found to have the highest correlation with repetition of mammography (r =0.4). Among the demographic variables, marital status (β= -0.1) and family history of breast cancer (β=0.1) had the most direct and significant impact on repetition of mammography (P mammography (P mammography, but the results did not prove any relationship with risk perception. Further studies are needed to assess the effect of risk perception and knowledge about time interval on the initiation and continuation of mammography.

  2. [Assessment of the cervical cancer screening in the Family Health Strategy in Amparo, São Paulo State, Brazil].

    Science.gov (United States)

    Vale, Diama Bhadra Andrade Peixoto do; Morais, Sirlei Siani; Pimenta, Aparecida Linhares; Zeferino, Luiz Carlos

    2010-02-01

    Uterine cervical cancer mortality has not been declining. The territorial distribution and registration of families in Brazil's Family Health Strategy help identify women that have performed a Pap smear or that have not had one for more than three years. This study analyzed whether cervical cancer screening in Amparo, São Paulo State, Brazil, made progress in complying with the prevailing guidelines during the seven years of experience with the Strategy. The annual examination rate remained high, with a slight trend towards greater intervals between follow-up tests. Distribution of tests tended to increase in the 40-59-year age bracket and decrease in the over-60 age group, while annual coverage tended to decrease. The proportions of excess tests varied from 61.2% to 65.5%. Concluding, the upgrading of cervical cancer screening was slight, and did not change the opportunistic pattern of follow-up tests. Considering that community health agents can act to increase the coverage of these measures, it is essential to train them for this work.

  3. 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.

  4. Delivering a very brief psychoeducational program to cancer patients and family members in a large group format.

    Science.gov (United States)

    Cunningham, A J; Edmonds, C V; Williams, D

    1999-01-01

    It is well established that brief psychoeducational programs for cancer patients will significantly improve mean quality of life. As this kind of adjunctive treatment becomes integrated into general cancer management, it will be necessary to devise cost-effective and efficacious programs that can be offered to relatively large numbers of patients. We have developed a very brief 4-session program that provides this service to 40-80 patients and family members per month (and seems capable of serving much larger numbers, depending on the capacity of the facility in which they assemble). Patients meet in a hospital auditorium for a large group, lecture-style program that offers training in basic coping skills: stress management, relaxation training, thought monitoring and changing, mental imagery and goal setting. Over the first year we have treated 363 patients and 150 family members. Improvements were assessed by changes in the POMS-Short Form, and both patients and family members were found to improve significantly over the course of the program. While this is not a randomized comparison, it suggests that the benefits gained from a large group in a classroom are not substantially less than the improvements that have been documented in the usual small group format, where more interactive discussions are possible.

  5. Aldo-keto Reductase Family 1 B10 as a Novel Target for Breast Cancer Treatment

    Science.gov (United States)

    2010-08-01

    cells via identifying the functional domain(s). Body 1) AKR1B10 silencing inhibits breast cancer cells BT-20 growth in culture and...Laboratory of Chemical Biology, Guangdong Province, Tsinghua University Graduate School at Shenzhen , Guangdong 518055 and 6School of Medicine, Tsinghua...breast cancer. Silencing of AKR1B10 in BT-20 human breast cancer cells inhibited cell growth in culture and tumorigenesis in female nude mice. Taken

  6. 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.

  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. 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.

  9. 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.

  10. Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ripa, Rasmus S.; Katballe, Niels; Wikman, Friedrik P.;

    2005-01-01

    The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions...... of a single amino acid codon have previously been published as assumed pathogenic. The objective of this study was to determine if an MSH2 3 base pair in-frame deletion (N596del) could be used in presymptomatic screening of at-risk individuals. We report on five HNPCC families with the N596del mutation....... The results support the hypothesis that N596del is the disease causing mutation and not a clinically silent variation. On this basis, the application of the MSH2 N596del mutation, in presymptomatic screening of HNPCC families, is recommended....

  11. Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, and Urologic Cancers

    Science.gov (United States)

    2017-01-13

    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

  12. Identification of a breast cancer family double heterozygote for RAD51C and BRCA2 gene mutations

    DEFF Research Database (Denmark)

    Ahlborn, Lise B; Steffensen, Ane Y; Jønson, Lars;

    2015-01-01

    Next-generation sequencing has entered routine genetic testing of hereditary breast cancer. It has provided the opportunity to screen multiple genes simultaneously, and consequently has identified new complex genotypes. Here we report the first identification of a woman double heterozygote...... described before and mini-gene splicing experiments revealed that the mutation results in skipping of exon 26 containing a part of the DNA-binding domain. We conclude that the woman has two potential disease-causing mutations and that predictive testing of family members should include both the RAD51C...

  13. 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.

  14. 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

  15. Pregnane X Receptor and Cancer: Context-Specificity is Key

    Science.gov (United States)

    Pondugula, Satyanarayana R.; Pavek, Petr; Mani, Sridhar

    2016-01-01

    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. PMID:27617265

  16. 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.

  17. Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function.

    Science.gov (United States)

    Wadhwa, R; Sugihara, T; Yoshida, A; Nomura, H; Reddel, R R; Simpson, R; Maruta, H; Kaul, S C

    2000-12-15

    MKT-077, a cationic rhodacyanine dye analogue has been under preclinical cancer therapeutical trials because of its selective toxicity to cancer cells. Its cellular targets and mechanism of action remain poorly understood. Here we report that MKT-077 binds to an hsp70 family member, mortalin (mot-2), and abrogates its interactions with the tumor suppressor protein, p53. In cancer cells, but not in normal cells, MKT-077 induced release of wild-type p53 from cytoplasmically sequestered p53-mot-2 complexes and rescued its transcriptional activation function. Thus, MKT-077 may be particularly useful for therapy of cancers with wild-type p53.

  18. [Selenium and oxidative stress in cancer patients].

    Science.gov (United States)

    Gorozhanskaia, É G; Sviridova, S P; Dobrovol'skaia, M M; Zybrikhina, G N; Kashnia, Sh R

    2013-01-01

    In order to identify the features of violations of free-radical processes in blood serum of 94 untreated cancer patients with different localization of the tumor (cancer of the stomach, colon, breast, ovarian, hemoblastoses) were determined selenium levels and indicators of oxidative stress (sum of metabolites of nitrogen--NOx, the level of superoxide dismutase--Cu/ZnSOD and malondiialdehyde-MDA, and the activity of catalase). In addition, 40 patients with malignant liver disease and clinical signs of liver failure in the early postoperative period was carried out a comparative evaluation of the efficacy of selenium-containing drug "Selenaze" (sodium selenite pentahydrate). It was found that selenium levels in cancer patients by 25-30% below the norm of 110-120 mg/l at a rate of 73.0 +/- 2.6 mg/l. Low levels of NOx was detected in patients with all tumor localizations (22.1 +/- 1.1 microM, with normal range 28.4 +/- 0.9 microM). The exceptions were patients with extensive malignant process in the liver, in which the NOx levels were significantly higher than normal (p selenium levels by 10-12%, which was accompanied by a decrease in the content of SOD and NOx, and contributed to earlier recovery of detoxic and synthetic liver function. These findings point to an intensification of oxidative stress and metabolic disorders in the malignant process, which is the basis for metabolic correction.

  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. Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ripa, R S; Katballe, N; Wikman, F P

    2005-01-01

    The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions of a s....... The results support the hypothesis that N596del is the disease causing mutation and not a clinically silent variation. On this basis, the application of the MSH2 N596del mutation, in presymptomatic screening of HNPCC families, is recommended.......The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions...... of a single amino acid codon have previously been published as assumed pathogenic. The objective of this study was to determine if an MSH2 3 base pair in-frame deletion (N596del) could be used in presymptomatic screening of at-risk individuals. We report on five HNPCC families with the N596del mutation...

  1. Family Resilience:Concept and Application in Families with a Cancer Patient (review)%家庭韧性及其在癌症患者中的研究进展

    Institute of Scientific and Technical Information of China (English)

    王文慧; 姜喆; 杨芷

    2015-01-01

    Family resilience explores the positive resources of a family under adversity. This paper expounded the origin, concept, relat-ed factors, framework and implications of family resilience, especially the family resilience in families with a cancer patient.%家庭韧性是从积极的视角探讨不利处境的家庭借以恢复家庭健康的优势力量与资源。本文从家庭韧性的起源、家庭韧性概念、家庭韧性因素、家庭韧性的相关理论及癌症患者家庭韧性的相关研究及家庭韧性模式的应用等方面做一综述。

  2. 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.

  3. ABCC4与人类肿瘤%ATP-binding cassette transporter family class C4 and human cancer

    Institute of Scientific and Technical Information of China (English)

    石妮; 赵晓航

    2011-01-01

    ATP-binding cassette transporter family class C4 (ABCC4) is known as a member of the ATP-binding cassette transporter super-family, involved in the active transport of endogenous anions and xenobiotic, which is not normally produced or expected to be present in human, such as antibiotics. Recently it has been found that the copy number variations of Abcc4 gene and overexpression of ABCC4 protein in many kinds of human cancers, which might involved in tumorigenesis, progress and chemotherapeutic response. This review will focus on the ectopic expression of Abcc4 in human cancer and the potential role of ABCC4 in tumorigenesis and progress.%ABCC4(ATP-binding cassette transporter family class C4,ABCC4)是ABC蛋白家族成员,主要参与转运机体物质代谢中产生的有机阴离子和一些异型生物质等生物学功能.近年研究发现某些人类肿瘤存在Abcc4基因的拷贝数变异,主要表现为Abcc4基因拷贝数增加和ABCC4蛋白过表达,这些改变与肿瘤发生发展、耐药,以及治疗疗效具有相关性.该文综述了Abcc4基因的拷贝数变异和异常表达与肿瘤生物学特性的关系,探讨ABCC4在肿瘤发生发展中的作用机制.

  4. Family history of cancer and seizures in young children with brain tumors: a report from the Childrens Cancer Group (United States and Canada).

    Science.gov (United States)

    Kuijten, R R; Strom, S S; Rorke, L B; Boesel, C P; Buckley, J D; Meadows, A T; Bunin, G R

    1993-09-01

    The occurrence of cancer and neurological disorders in first- and second-degree relatives of children in the United States and Canada diagnosed with brain tumor before age six was investigated. A pair-matched case-control study with 155 astrocytoma and 166 primitive neuroectodermal tumor (PNET) cases was performed. Cases were identified through the Childrens Cancer Group. Controls were selected by random-digit dialing and matched to cases on age, race, and telephone area code and exchange. Childhood cancers were more common in PNET relatives compared with the general population (standardized incidence ratio [SIR] = 2.5, 95 percent confidence interval [CI] 1.1-4.8, P = 0.02) and with control relatives (odds ratio [OR] = 3.0, CI = 0.5-30, P = 0.29). For astrocytoma, nonsignificant excesses of brain tumor, leukemia/lymphoma, and childhood cancer occurred among case relatives compared with control relatives, but not compared with the general population. Astrocytoma cases were significantly more likely than controls to have a relative with seizures (OR = 2.5, CI = 1.2-4.9, P = 0.009), especially childhood seizures (OR = 3.4, CI = 1.2-12, P = 0.02), epilepsy (OR = 3.0, CI = 0.9-13, P = 0.08), and febrile convulsions (OR = 4.5, CI = 0.9-43, P = 0.07). A family history of stroke was not a risk factor for either type of brain tumor. These results suggest that some childhood brain tumors may result from a genetic susceptibility and that some risk factors may affect childhood astrocytoma and PNET differently.

  5. Past recreational physical activity, body size, and all-cause mortality following breast cancer diagnosis: results from the Breast Cancer Family Registry.

    Science.gov (United States)

    Keegan, Theresa H M; Milne, Roger L; Andrulis, Irene L; Chang, Ellen T; Sangaramoorthy, Meera; Phillips, Kelly-Anne; Giles, Graham G; Goodwin, Pamela J; Apicella, Carmel; Hopper, John L; Whittemore, Alice S; John, Esther M

    2010-09-01

    Few studies have considered the joint association of body mass index (BMI) and physical activity, two modifiable factors, with all-cause mortality after breast cancer diagnosis. Women diagnosed with invasive breast cancer (n = 4,153) between 1991 and 2000 were enrolled in the Breast Cancer Family Registry through population-based sampling in Northern California, USA; Ontario, Canada; and Melbourne and Sydney, Australia. During a median follow-up of 7.8 years, 725 deaths occurred. Baseline questionnaires assessed moderate and vigorous recreational physical activity and BMI prior to diagnosis. Associations with all-cause mortality were assessed using Cox proportional hazards regression, adjusting for established prognostic factors. Compared with no physical activity, any recreational activity during the 3 years prior to diagnosis was associated with a 34% lower risk of death [hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.51-0.85] for women with estrogen receptor (ER)-positive tumors, but not those with ER-negative tumors; this association did not appear to differ by race/ethnicity or BMI. Lifetime physical activity was not associated with all-cause mortality. BMI was positively associated with all-cause mortality for women diagnosed at age > or =50 years with ER-positive tumors (compared with normal-weight women, HR for overweight = 1.39, 95% CI: 0.90-2.15; HR for obese = 1.77, 95% CI: 1.11-2.82). BMI associations did not appear to differ by race/ethnicity. Our findings suggest that physical activity and BMI exert independent effects on overall mortality after breast cancer.

  6. 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...... the survival of tumorigenic as well as nontumorigenic cells depended on Hsc70. Cancer cells depleted for Hsp70 and Hsp70-2 displayed strikingly different morphologies (detached and round vs. flat senescent-like), cell cycle distributions (G2/M vs. G1 arrest) and gene expression profiles. Only Hsp70-2 depletion...

  7. Measurement of socio-economic status in families of children with cancer in Guatemala.

    Science.gov (United States)

    De Pernillo, M; Rivas, S; Fuentes, L; Antillon, F; Barr, R D

    2014-11-01

    The prospects for survival of children in low and middle income countries are linked to their families socio-economic status (SES), of which income is only one component. Developing a comprehensive measure of SES is required. Informed by clinical experience, a 15-item instrument was designed in Guatemala to categorize SES by five levels in each item. Almost 75% of families attending the Unidad Nacional de Oncología Pediátrica were in the lowest three of six categories, providing a framework for stratified financial and nutritional support. The measure of SES offers an opportunity for examining associations with health outcomes throughout Latin America.

  8. 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

  9. Exome sequencing of germline DNA from non-BRCA1/2 familial breast cancer cases selected on the basis of aCGH tumor profiling.

    Directory of Open Access Journals (Sweden)

    Florentine S Hilbers

    Full Text Available The bulk of familial breast cancer risk (∼70% cannot be explained by mutations in the known predisposition genes, primarily BRCA1 and BRCA2. Underlying genetic heterogeneity in these cases is the probable explanation for the failure of all attempts to identify further high-risk alleles. While exome sequencing of non-BRCA1/2 breast cancer cases is a promising strategy to detect new high-risk genes, rational approaches to the rigorous pre-selection of cases are needed to reduce heterogeneity. We selected six families in which the tumours of multiple cases showed a specific genomic profile on array comparative genomic hybridization (aCGH. Linkage analysis in these families revealed a region on chromosome 4 with a LOD score of 2.49 under homogeneity. We then analysed the germline DNA of two patients from each family using exome sequencing. Initially focusing on the linkage region, no potentially pathogenic variants could be identified in more than one family. Variants outside the linkage region were then analysed, and we detected multiple possibly pathogenic variants in genes that encode DNA integrity maintenance proteins. However, further analysis led to the rejection of all variants due to poor co-segregation or a relatively high allele frequency in a control population. We concluded that using CGH results to focus on a sub-set of families for sequencing analysis did not enable us to identify a common genetic change responsible for the aggregation of breast cancer in these families. Our data also support the emerging view that non-BRCA1/2 hereditary breast cancer families have a very heterogeneous genetic basis.

  10. Contribution of the PALB2 c.2323C>T [p.Q775X] Founder mutation in well-defined breast and/or ovarian cancer families and unselected ovarian cancer cases of French Canadian descent

    Directory of Open Access Journals (Sweden)

    Tischkowitz Marc

    2013-01-01

    Full Text Available Abstract Background The PALB2 c.2323C>T [p.Q775X] mutation has been reported in at least three breast cancer families and breast cancer cases of French Canadian descent and this has been attributed to common ancestors. The number of mutation-positive cases reported varied based on criteria of ascertainment of index cases tested. Although inherited PALB2 mutations are associated with increased risks of developing breast cancer, risk to ovarian cancer has not been fully explored in this demographically unique population. Methods We screened the PALB2 p.Q775X variant in 71 families with at least three cases of breast cancer (n=48 or breast and ovarian cancers (n=23 that have previously been found negative for at least the most common BRCA1 and BRCA2 mutations reported in the French Canadian population and in 491 women of French Canadian descent who had invasive ovarian cancer and/or low malignant potential tumors of the major histopathological subtypes. Results We identified a PALB2 p.Q775X carrier in a breast cancer family, who had invasive ductal breast carcinomas at 39 and 42 years of age. We also identified a PALB2 p.Q775X carrier who had papillary serous ovarian cystadenocarcinoma at age 58 among the 238 serous subtype ovarian cancer cases investigated, who also had breast cancer at age 52. Conclusion Our findings, taken together with previous reports, support adding PALB2 c.2323C>T p.Q775X to the list of cancer susceptibility genes for which founder mutations have been identified in the French Canadian population.

  11. A Study of Black and White Men With a Family History of Prostate Cancer

    Science.gov (United States)

    2002-03-01

    es correcta o incorrecta. Estamos interesados en saber que es lo que usted siente y cree sobre el cAncer de la pr6stata. D:\\NILSA\\lProstate...o hijo. Tener un familiar diagnosticado antes de la edad de 60 anos. Ser Afro-Americano Usted debe de saber que hacer ejercicio y una dieta baja en

  12. 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

  13. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion.

    Science.gov (United States)

    Cekanova, Maria; Fernando, Romaine I; Siriwardhana, Nalin; Sukhthankar, Mugdha; De la Parra, Columba; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J; Wade, Paul A; Saxton, Arnold M; Donnell, Robert M; Pestell, Richard G; Dharmawardhane, Suranganie; Wimalasena, Jay

    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.

  14. 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

    of cancer development. Method:  Follow-up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included chi(2) test, actuarial method and Kaplan-Meier analysis. Results:  Among 304 patients, 261 (86%) had more than one endoscopy. The median follow-up was 14 years...

  15. 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

    of cancer development. Method: Follow-up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included chi(2) test, actuarial method and Kaplan-Meier analysis. Results: Among 304 patients, 261 (86%) had more than one endoscopy. The median follow-up was 14 years...

  16. The MUC gene family: Their role in diagnosis and early detection of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Löhr Matthias

    2003-01-01

    Full Text Available Abstract The early diagnosis of pancreatic cancer, as well as distinguishing between chronic pancreatitis and malignant pancreatic disease, remains still a clinical problem. Presently, there is no specific tumor marker for diagnosing pancreatic cancer. Mucin-associated marker like CA 19-9 are the most widely available pancreatic cancer tumor marker, but its value as a screening marker is limited by its reduced specificity. Mucins (MUCs are heavily glycosylated, high molecular weight glycoproteins with an aberrant expression profile in various malignancies. This review considers briefly the potential use of the mucin expression pattern in diagnosis of pancreatic neoplasm. The overview will point out the present knowledge about changes in the mucin gene expression in pancreatic intraepithelial neoplasia (PanINs as precursor lesions and in pancreatic adenocarcinoma, compared to normal pancreas and chronic pancreatitis and the potential role for differentiating chronic pancreatitis from pancreatic cancer. Furthermore, the potential use of MUCs in the diagnosis and differentiation of intraductal papillary-mucinous neoplasm's (IPMNs will be discussed.

  17. 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...

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

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Gerdes, A. M.; Mosgaard, B.;

    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...

  19. Differential expression of the UGT1A family of genes in stomach cancer tissues.

    Science.gov (United States)

    Cengiz, Beyhan; Yumrutas, Onder; Bozgeyik, Esra; Borazan, Ersin; Igci, Yusuf Ziya; Bozgeyik, Ibrahim; Oztuzcu, Serdar

    2015-08-01

    Uridine 5'-diphospho-glucuronosyltransferases (UGT) are the key players in the biotransformation of drugs, xenobiotics, and endogenous compounds. Particularly, UDP-glucuronosyltransferase 1A (UGT1A) participates in a wide range of biological and pharmacological processes and plays a critical role in the conjugation of endogenous and exogenous components. Thirteen alternative splicing products were produced from UGT1A gene locus designated as UGT1A1 and UGT1A3-10. A growing amount of evidence suggests that they have important roles in the carcinogenesis which is well documented by colon, liver, pancreas, and kidney cancer studies. Here, we report differential expressions of UGT1A genes in normal and tumor tissues of stomach cancer patients. Total numbers of 49 patients were enrolled for this study, and expression analysis of UGT1A genes was evaluated by the real-time PCR method. Accordingly, UGT1A1, UGT1A8, and UGT1A10 were found to be upregulated, and UGT1A3, UGT1A5, UGT1A7, and UGT1A9 were downregulated in stomach tumors. No expression changes were observed in UGT1A4. Also, UGT1A6 transcription variants were significantly upregulated in stomach cancer tissues compared to normal stomach tissue. Additionally, UGT1A7 gene showed highest expression in both normal and tumoral tissues, and interestingly, UGT1A7 gene expression was significantly reduced in stage II patients as compared to other patients. In conclusion, UGT1A genes are differentially expressed in normal and tumoral stomach tissues and expression changes of these genes may affect the development and progression of various types of cancer including the cancer of the stomach.

  20. Unclassified sequence variants (UVS and genetic predisposition to cancer

    Directory of Open Access Journals (Sweden)

    Yves-Jean Bignon

    2011-06-01

    Full Text Available Hereditary breast and ovarian cancers are mainly attributable to predisposition genes whose germinal mutations are responsible for the disease. The most common genes associated with breast/ovarian cancer are BRCA1 and BRCA2 but at least 20 other genes of medium of high penetrance have been associated with these types of cancer. Lifetime risk of breast cancer for BRCA mutations carriers approaches 90%. Appropriate medical follow-up is therefore essential for women carrying mutations in these genes. BRCA mutational spectrum has not been entirely characterized but not all sequence variants are pathogenic. These are classified as benign polymorphisms or unclassified variants (UV with unknown pathological potential. To date, 43,5% of over 3500 genetic variants BRCA1 and BRCA2 are reported as having uncertain clinical significance. Whether one sequence variant has or not a pathogenicity implication is often a hard decision to take, involving important consequences for diagnosis and medical follow-up. Here we present several cases of unclassified sequence variants detection and interpretation by in-silico analysis.

  1. 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.

  2. Growing in times of grief: attachment modulates bereaved adults' posttraumatic growth after losing a family member to cancer.

    Science.gov (United States)

    Xu, Wei; Fu, Zhongfang; He, Li; Schoebi, Dominik; Wang, Jianping

    2015-11-30

    This study explored whether attachment moderated the relationship between grief and posttraumatic growth. A total of 240 Chinese adults who have lost a family member to cancer reported on their grief (Prolonged Grief Questionnaire-13; PG-13), posttraumatic growth (Posttraumatic Growth Inventory; PTGI) and attachment (Experiences in Close Relationships; ECR). The results suggested that bereaved individuals who scored high on attachment anxiety showed a substantial and positive relationship between grief and posttraumatic growth, while their less anxiously attached counterparts showed no such association. Attachment avoidance was not significantly related to the association between grief and posttraumatic growth. Findings indicated that individuals high in attachment anxiety have the potential to benefit and gain from the process of adapting to the loss. The implications of the results for relevant research and grief counseling were discussed.

  3. 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

  4. The Interdependence of Advanced Cancer Patients’ and Their Family Caregivers’ Mental Health, Physical Health, and Self-Efficacy Over Time

    Science.gov (United States)

    Kershaw, Trace; Ellis, Katrina R.; Yoon, Hyojin; Schafenacker, Ann; Katapodi, Maria; Northouse, Laurel

    2016-01-01

    Background The challenges of advanced cancer have health implications for patients and their family caregivers from diagnosis through end-of-life. The nature of the patient/caregiver experience suggests that their mental and physical health may be interdependent, but limited empirical evidence exists. Purpose This study used Social Cognitive Theory as a framework to investigate individual and interpersonal influences on patients’ and their family caregivers’ mental health, physical health, and self-efficacy as individuals to manage the challenges of advanced disease over time. Methods Patients and caregivers (484 patient-caregiver dyads) completed surveys at baseline, 3 months and 6 months. Longitudinal dyadic analysis techniques were used to examine (i) the influence that patients and caregivers had on their own mental health, physical health, and self-efficacy (actor effects) and (ii) the influence that they had on each other’s health outcomes (partner effects). We also examined the influence of self-efficacy on mental and physical health over time. Results Consistent with our hypotheses, each person’s mental health, physical health, and self-efficacy had significant effects on their own outcomes over time (actor effects). Patients and caregivers influenced one another’s mental and physical health (partner effects), but not their self-efficacy. In addition, patients and caregivers with higher self-efficacy had better mental health, and their partners had better physical health. Conclusions Patient and caregiver mental and physical health were interdependent. Each person’s cancer-related self-efficacy influenced their own mental and physical health. However, a person’s self-efficacy did not influence the other person’s self-efficacy. PMID:26489843

  5. Mobile Phone Technology to Increase Genetic Counseling for Women with Ovarian Cancer and Their Families

    Science.gov (United States)

    2015-06-01

    2. What is your race? □ White □ Black or African American □ Other: __________________________ 3. Are you of Hispanic, Latino/a, or of Spanish ...overall study objective is to develop and assess the feasibility and effectiveness of a theory -based intervention aimed to encourage ovarian cancer...meetings which resulted in a preliminary draft of the 7-day text message and video intervention. Following completion of the intervention, we will

  6. 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.

  7. 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.

  8. 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.

  9. Mutational analyses of BRCA1 and BRCA2 with Ashkenazi and non-Ashkenazi Jewish women with familial breast and ovarian cancer

    NARCIS (Netherlands)

    Shiri-Sverdlov, R; Oefner, P; Green, L; Baruch, RG; Wagner, T; Kruglikova, A; Haitchick, S; Hofstra, RMW; Papa, MZ; Mulder, [No Value; Rizel, S; Sade, RBB; Dagan, E; Abdeen, Z; Goldman, B; Friedman, E

    2000-01-01

    In Ashkenazi (East European) Jews, three predominant mutations in BRCA1 (185delAG and 5382insC) and BRCA2 (6174-delT) account for the majority of germline mutations in high risk breast and/or ovarian cancer families. Among non-Ashkenazi Jews, the 185delAG, Tyr978Ter, and a handful of "private" mutat

  10. Accuracy of Colon Capsule Endoscopy in Detecting Colorectal Polyps in Individuals with Familial Colorectal Cancer: Could We Avoid Colonoscopies?

    Science.gov (United States)

    Alvarez-Urturi, Cristina; Fernández-Esparrach, Gloria; Ibáñez, Inés Ana; Rodríguez De Miguel, Cristina; Dedeu, Josep Maria; Bessa, Xavier; Córdova, Henry; Pellisé, Maria; Balaguer, Francesc; Ginés, Angels; Barranco, Luis; Araujo, Isis K.; Andreu, Montserrat; Llach, Josep

    2017-01-01

    Background. Individuals with a family history of colorectal cancer (CRC) have an increased risk of CRC. We evaluated the diagnostic yield of CCE in the detection of lesions and also two different colon preparations. Methods. A prospective multicenter study was designed to assess CCE diagnostic yield in a cohort of asymptomatic individuals with a family history of CRC. CCE and colonoscopy were performed on the same day by 2 endoscopists who were blinded to the results of the other procedure. Results. Fifty-three participants were enrolled. The sensitivity, specificity, PPV, and NPV of CCE for detecting advanced adenomas were 100%, 98%, 67%, and 100%. Sensitivity, specificity, PPV, and NPV of CCE for the diagnosis of individuals with polyps were 87%, 97%, 93%, and 88%, respectively. CCE identify 100% of individuals with significant or advanced lesions. Overall cleanliness was adequate by 60.7% of them. The PEG-ascorbic boost seems to improve colon cleanliness, with similar colonic transit time. Conclusion. CCE is a promising tool, but it has to be considered as an alternative technique in this population in order to reduce the number of colonoscopies performed. More studies are needed to understand appropriate screening follow-up intervals and optimize the bowel preparation regimen. PMID:28265285

  11. 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 ...

  12. 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 ...

  13. 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.

  14. The Family Living with Prostate Cancer - The Wife`s Persp