Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers
Year: 2011
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. METHODS: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. RESULTS: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. CONCLUSION: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. IMPACT: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk.
Authors: Amanda B. Spurdle, Louise Marquart, Lesley McGuffog, Sue Healey, Olga Sinilnikova, Fei Wan, Xiaoqing Chen, Jonathan Beesley, Christian F. Singer, Anne-Catharine Dressler, Daphne Gschwantler-Kaulich, Joanne L. Blum, Nadine Tung, Jeff Weitzel, Henry Lynch, Judy Garber, Douglas F. Easton, Susan Peock, Margaret Cook, Clare T. Oliver, Debra Frost, Don Conroy, D. Gareth Evans, Fiona Lalloo, Ros Eeles, Louise Izatt, Rosemarie Davidson, Carol Chu, Diana Eccles, Christina G. Selkirk, Mary Daly, Claudine Isaacs, Dominique Stoppa-Lyonnet, Olga M. Sinilnikova, Bruno Buecher, Muriel Belotti, Sylvie Mazoyer, Laure Barjhoux, Carole Verny-Pierre, Christine Lasset, Hélène Dreyfus, Pascal Pujol, Marie-Agnès Collonge-Rame, for the GEMO Study Collaborators, Matti A. Rookus, Senno Verhoef, Mieke Kriege, Nicoline Hoogerbrugge, Margreet G. E. M. Ausems, Theo A. van Os, Juul Wijnen, Peter Devilee, Hanne E. J. Meijers-Heijboer, Marinus J. Blok, Tuomas Heikkinen, Heli Nevanlinna, Anna Jakubowska, Jan Lubiński, Tomasz Huzarski, Tomasz Byrski, Francine Durocher, Fergus J. Couch, Noralane M. Lindor, Xianshu Wang, Mads Thomassen, Susan Domchek, Kate Nathanson, MA Caligo, Helena Jernström, Annelie Liljegren, Hans Ehrencrona, Per Karlsson, for SWE-BRCA, Patricia A. Ganz, Olufunmilayo I. Olopade, Gail Tomlinson, Susan Neuhausen, Antonis C. Antoniou, Georgia Chenevix-Trench, Timothy R. Rebbeck
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Breast Cancer Research Foundation, Nebraska Department of Health and Human Services, Canadian Breast Cancer Research Alliance, Cancer Research UK, National Institute for Health and Care Research, National Breast Cancer Foundation, National Institutes of Health, Canadian Institutes of Health Research, Medical Research Council, National Health and Medical Research Council, National Cancer Institute
Awards: How can the risk of breast cancer be reduced in those with a strong family history of the disease?, A genome-wide association study for breast cancer in BRCA1 mutation carriers, G1232765841, NIHR Senior Investigator Award, G1357738703, G1616122786, G1998022053, G2291128078, G2325870751, G236237718, Prophytactic surgery in carriers of BRCA 1/2 mutations, G2640026379, G3182923297, G3188551179, Clinical Outcomes In Individuals With An Inherited Predisposition To Breast Cancer, G3355877513, G389926461, G424082930, G431899019, EDRN: Clinical Epidemiology & Validation Centers, G4333708648, Modifiers of Cancer Risk in BRCA 1/2 Mutation Carriers, G5828200131, G5865683244, G5950516432, G6279653796, G6616185778, G6642005126, G6776401840, G704544610, G7182136598, Clinical Cancer Genetics Community Network: A Sustainable Research Partnership, G740476103, kConFab Clinical Follow-Up Project, G8548705263, G864128669, Mayo Clinic Breast Cancer SPORE, Genetic Epidemiology of Breast Cancer: BRCA1 and BRCA2
OpenAlex ID: W2136116577