Alcohol Consumption, Cigarette Smoking, and Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Results from The BRCA1 and BRCA2 Cohort Consortium

Hongyan Li, Mary Beth Terry, Antonis C. Antoniou, Kelly Anne Phillips, Karin Kast, Thea M. Mooij, Christoph Engel, Catherine Noguès, Dominique Stoppa-Lyonnet, Christine Lasset, Pascaline Berthet, Veronique Mari, Olivier Caron, Daniel Barrowdale, Debra Frost, Carole Brewer, D. Gareth Evans, Louise Izatt, Lucy Side, Lisa WalkerMarc Tischkowitz, Mark T. Rogers, Mary E. Porteous, Katie Snape, Hanne E.J. Meijers-Heijboer, Johan J.P. Gille, Marinus J. Blok, Nicoline Hoogerbrugge, Mary B. Daly, Irene L. Andrulis, Saundra S. Buys, Esther M. John, Sue Anne McLachlan, Michael Friedlander, Yen Y. Tan, Ana Osorio, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Christian F. Singer, Edith Olah, Marie Navratilova, Lenka Foretova, Anne Marie Gerdes, Marie José Roos-Blom, Brita Arver, Håkan Olsson, Rita K. Schmutzler, John L. Hopper, Roger L. Milne, Douglas F. Easton, Flora E. Van Leeuwen, Matti A. Rookus, Nadine Andrieu, David E. Goldgar, GENEPSO study, EMBRACE Study, HEBON Investigators, KConFab Investigators

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Background: Tobacco smoking and alcohol consumption have been intensively studied in the general population to assess their effects on the risk of breast cancer, but very few studies have examined these effects in BRCA1 and BRCA2 mutation carriers. Given the high breast cancer risk for mutation carriers and the importance of BRCA1 and BRCA2 in DNA repair, better evidence on the associations of these lifestyle factors with breast cancer risk is essential. Methods: Using a large international pooled cohort of BRCA1 and BRCA2 mutation carriers, we conducted retrospective (5,707 BRCA1 mutation carriers and 3,525 BRCA2 mutation carriers) and prospective (2,276 BRCA1 mutation carriers and 1,610 BRCA2 mutation carriers) analyses of alcohol and tobacco consumption using Cox proportional hazards models. Results: For both BRCA1 and BRCA2 mutation carriers, none of the smoking-related variables was associated with breast cancer risk, except smoking for more than 5 years before a first full-term pregnancy (FFTP) when compared with parous women who never smoked. For BRCA1 mutation carriers, the HR from retrospective analysis (HR R) was 1.19 [95% confidence interval (CI), 1.02-1.39] and the HR from prospective analysis (HR P) was 1.36 (95% CI, 0.99-1.87). For BRCA2 mutation carriers, smoking for more than 5 years before an FFTP showed an association of a similar magnitude, but the confidence limits were wider (HR R = 1.25; 95% CI, 1.01-1.55 and HR P = 1.30; 95% CI, 0.83-2.01). For both carrier groups, alcohol consumption was not associated with breast cancer risk. Conclusions: The finding that smoking during the prereproductive years increases breast cancer risk for mutation carriers warrants further investigation.

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