Mutations in BRCA1 and BRCA2 genotype do not uniformly produce a cancer phe-notype. Estimates of risk for carriers vary depending on the population examined, patient age, and specific mutation involved. Overall in high-risk, clinic-based families, high penetrance of BRCA1 mutations convey more than 90% lifetime risk of developing either breast or ovarian cancer (78). For BRCA2, the risk of developing either breast or ovarian cancer by the age of 70 has been reported to be 88% (121).

For BRCA-associated breast cancer, reported risk ranges widely from 35 to 75% (97,122-124). In large families with multiple cases of breast cancer carrying mutations in BRCA1, studied by the Breast Cancer Linkage Consortium, the risk of developing breast cancer was more than 50% by the age of 50, and 82% by the age of 70, compared with only 11% in the general population (78). In comparison, the risk for BRCA2

carriers reached 28% by the age of 50, and 84% by the age of 70 (121). The risk of cancer in mutation carriers in the general population is lower, yielding an overall penetrance for breast cancer of about 50-70% (123).

For ovarian cancer, the reported lifetime risk for mutation carriers ranges from 15 to 60% (78,121,123,125). For those in high-risk families carrying BRCA1 mutations, the risk for developing ovarian cancer by the age of 70 has been estimated to be 44-63%, compared with only 1.4% in the general population (78). The risk for BRCA2 carriers from similar families was 27% by age 70 (121). Given that penetrance is lower in mutation carriers from the general population, studies of women in the Ashkenazi Jewish population selected for no family history has revealed risk for ovarian cancer to be 16-37% (123,126).

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