Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers

Amanda B. Spurdle, Louise Marquart, Lesley McGuffog, Sue Healey, Olga M. Sinilnikova, Fei Wan, Xiaoqing Chen, Jonathan Beesley, Christian F. Singer, Anne-Catharine Dressler, Daphne Gschwantler-Kaulich, Joanne L. Blum, Nadine Tung, Jeff Weitzel, Henry T. Lynch, Judy Garber, Douglas F. Easton, Susan Peock, Margaret Cook, Clare T. OliverDebra Frost, Don Conroy, D. Gareth Evans, Fiona Lalloo, Ros Eeles, Louise Izatt, Rosemarie Davidson, Carol Chu, Diana Eccles, Christina G. Selkirk, Mary B. Daly, Claudine Isaacs, Dominique Stoppa-Lyonnet, Bruno Buecher, Muriel Belotti, Sylvie Mazoyer, Laure Barjhoux, Carole Verny-Pierre, Christine Lasset, Helene Dreyfus, Pascal Pujol, Marie-Agnes Collonge-Rame, Matti A. Rookus, Senno Verhoef, Mieke Kriege, Nicoline Hoogerbrugge, Margreet G. E. M. Ausems, Theo A. Mvan Os, Juul T. Wijnen, Peter Devilee, Hanne E. J. Meijers-Heijboer, Marinus J. Blok, Tuomas Heikkinen, Heli Nevanlinna, Anna Jakubowska, Jan Lubinski, Tomasz Huzarski, Tomasz Byrski, Francine Durocher, Fergus J. Couch, Noralane M. Lindor, Xianshu Wang, Mads Thomassen, Susan Domchek, Kate Nathanson, Maria A. Caligo, Helena Jernstrom, Annelie Liljegren, Hans Ehrencrona, Per Karlsson, Patricia A. Ganz, Olufunmilayo I. Olopade, Gail E. Tomlinson, Susan L. Neuhausen, Antonis C. Antoniou, Georgia Chenevix-Trench, Timothy R. Rebbeck*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)


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. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38.
Original languageEnglish
Pages (from-to)1032-1038
JournalCancer Epidemiology Biomarkers & Prevention
Issue number5
Publication statusPublished - May 2011

Cite this