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

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Spurdle, A.B. | Marquart, L. | Mcguffog, L. | Healey, Sue | Wan, F. | Chen, X. | Beesley, J. | Singer, C.F. | Dressler, A-C. | Gschwantler-Kaulich, D. | Blum, J.L. | Tung, N. | Weitzel, J. | Lynch, H. | Garber, J. | Easton, D.F. | Peock, S. | Margaret, C. | Clare, T.O. | Frost, D. | Conroy, D. | Evans, D.G. | Laloo, F. | Eeles, R. | Izatt, L. | Davidson, R. | Chu, C. | Eccles, D. | Selkirk, C.G. | Daly, M. | Isaacs, C. | Stoppa-Lyonnet, Dominique | Sinilnikova, O.M. | Buecher, B. | Belotti, M. | Mazoyer, S. | Barjhoux, L. | Verny-Pierre, C. | Lasset, Christine | Dreyfus, B. | Pujol, P. | Collonge-Rame, M-A. | Rookus, M.A. | Verhoef, S. | Kriege, M. | Hoogerbrugge, N. | Ausems M.G. E., M. | van Os, T.A. | Wijnen, J. | Devilee, P. | Meijers-Heijboer H.E., J. | Blok, M.J. | Heikkinen, T. | Nevanlinna, H. | Jakubowska, A. | Lubinski, J. | Huzarski, T. | Byrski, T. | Durocher, F. | Couch, F.J. | Lindor, N.M. | Wang, X. | Thomassen, M. | Domchek, S. | Nathanson, K. | Caligo, M.A. | Jernstrom, H. | Liljegren, A. | Ehrencrona, H. | Karlsson, P. | Ganz, P.A. | Olopade, O.I. | Tomlinson, G. | Neuhausen, S. | Antoniou, A. | Chenevix-Trench, G. | Rebbeck, T.R.

Edité par CCSD ; American Association for Cancer Research -

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.

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