Significantly lower rates of BRCA1/BRCA2 founder mutations in Ashkenazi women with sporadic compared with familial early onset breast cancer

To delineate the clinical, genetic and family history attributes in Jewish Ashkenazi women with early onset (<42 years) breast cancer we genotyped suc h women for the three predominant Jewish Ashkenazi mutations in BRCA1 (185d elAG and 5382insC) and BRCA2 (6174delT). The study cohort was composed of 1 72 women diagnosed with breast cancer at or before the age of 42 years, obt ained from the oncology department registry. Mutations were identified in 5 4 women (31%). Of 79 women with a positive family history for breast and/or ovarian cancer, and 93 with no such family history, 45 (57%) and 9 (10%), respectively, were mutation carriers (chi(2) = 46; P < 0.001). Contralatera l breast cancer occurred in 15 of 54 mutation carriers (28%) compared with 8 of 118 (7%) non-carriers (chi(2) = 14; P < 0.001). Early onset breast can cer ger se is a weak predictor of finding germ line mutation(s) in BRCA1 an d BRCA2, unless associated with a positive family history and/or bilaterali ty. (C) 2000 Elsevier Science Ltd. All rights reserved.