دورية أكاديمية
Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers.
| العنوان: | Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers. |
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| المؤلفون: | Walker, Logan C, Fredericksen, Zachary S, Wang, Xianshu, Tarrell, Robert, Pankratz, Vernon S, Lindor, Noralane M, Beesley, Jonathan, Healey, Sue, Chen, Xiaoqing, kConFab, Stoppa-Lyonnet, Dominique, Tirapo, Carole, Giraud, Sophie, Mazoyer, Sylvie, Muller, Danièle, Fricker, Jean-Pierre, Delnatte, Capucine, GEMO Study Collaborators, Schmutzler, Rita K, Wappenschmidt, Barbara, Engel, Christoph, Schönbuchner, Ines, Deissler, Helmut, Meindl, Alfons, Hogervorst, Frans B, Verheus, Martijn, Hooning, Maartje J, van den Ouweland, Ans Mw, Nelen, Marcel R, Ausems, Margreet Gem, Aalfs, Cora M, van Asperen, Christi J, Devilee, Peter, Gerrits, Monique M, Waisfisz, Quinten, HEBON, Szabo, Csilla I, ModSQuaD, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Harrington, Patricia, Evans, D Gareth, Lalloo, Fiona, Eeles, Ros, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Eccles, Diana, Ong, Kai-Ren, Cook, Jackie, EMBRACE, Rebbeck, Tim, Nathanson, Katherine L, Domchek, Susan M, Singer, Christian F, Gschwantler-Kaulich, Daphne, Dressler, Anne-Catharina, Pfeiler, Georg, Godwin, Andrew K, Heikkinen, Tuomas, Nevanlinna, Heli, Agnarsson, Bjarni A, Caligo, Maria Adelaide, Olsson, Håkan, Kristoffersson, Ulf, Liljegren, Annelie, Arver, Brita, Karlsson, Per, Melin, Beatrice, SWE-BRCA, Sinilnikova, Olga M, McGuffog, Lesley, Antoniou, Antonis C, Chenevix-Trench, Georgia, Spurdle, Amanda B, Couch, Fergus J |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1186/bcr2785 Breast Cancer Res |
| سنة النشر: | 2011 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Adult, Aged, 80 and over, Breast Neoplasms, Female, Gene Expression, Genes, BRCA2, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Risk Factors, Signal Transduction, Smad3 Protein, Transforming Growth Factor beta |
| الوصف: | INTRODUCTION: Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies. METHODS: We successfully genotyped 24 SNPs in a cohort of up to 4,724 BRCA1 and 2,693 BRCA2 female mutation carriers from 15 study groups and assessed whether these variants were associated with risk of breast cancer in BRCA1 and BRCA2 mutation carriers. RESULTS: SNPs in five of the 14 candidate genes showed evidence of association with breast cancer risk for BRCA1 or BRCA2 carriers (P < 0.05). Notably, the minor alleles of two SNPs (rs7166081 and rs3825977) in high linkage disequilibrium (r² = 0.77), located at the SMAD3 locus (15q22), were each associated with increased breast cancer risk for BRCA2 mutation carriers (relative risk = 1.25, 95% confidence interval = 1.07 to 1.45, P(trend) = 0.004; and relative risk = 1.20, 95% confidence interval = 1.03 to 1.40, P(trend) = 0.018). CONCLUSIONS: This study provides evidence that the SMAD3 gene, which encodes a key regulatory protein in the transforming growth factor beta signalling pathway and is known to interact directly with BRCA2, may contribute to increased risk of breast cancer in BRCA2 mutation carriers. This finding suggests that genes with expression associated with BRCA1 and BRCA2 mutation status are enriched for the presence of common genetic modifiers of breast cancer risk in these populations. ; RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/licenseTest which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text/xml; application/zip; application/pdf |
| اللغة: | English |
| العلاقة: | http://www.dspace.cam.ac.uk/handle/1810/238158Test |
| الإتاحة: | http://www.dspace.cam.ac.uk/handle/1810/238158Test |
| حقوق: | Walker et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: | edsbas.E01F2EB3 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |