Risk modifiers in carriers of BRCA1 mutations

The majority of, but not all, women with mutations in the BRCAI gene will be affected with breast or ovarian cancer by the age of 70. To establish whether known risk factors modify susceptibility to cancer in these women, we have studied the reproductive histories of 333 North American women who were found by haplotype analysis to carry BRCAI mutations. An increased risk for breast cancer was associated with low parity and with recent birth cohort. The risk of ovarian cancer decreased with increasing age at last childbirth; however, in contrast to the case for sporadic cancer, the risk of ovarian cancer in BRCAI carriers was found to increase significantly with increasing parity. (C) 1995 Wiley-Liss, Inc.