BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer

Ovarian cancer is a component of the autosomal-dominant hereditary breast-o varian cancer syndrome and may be due to a mutation in either the BRCA1 or BRCA2 genes. Two mutations in BRCA1 (185delAG and 5382insC) and one mutatio n in BRCA2 (6174delT) are common in the Ashkenazi Jewish population. One of these three mutations is present in similar to 2% of the Jewish population , Each mutation is associated with an increased risk of ovarian cancer, and it is expected that a significant proportion of Jewish women with ovarian cancer will carry one of these mutations. To estimate the proportion of ova rian cancers attributable to founding mutations in BRCA1 and BRCA2. in the Jewish population and the familial cancer risks associated with each, we in terviewed 213 Jewish women with ovarian cancer at 11 medical centers in Nor th America and Israel and offered these women genetic testing for the three founder mutations. To establish the presence of nonfounder mutations in th is population, we also completed the protein-truncation test on exon 11 of BRCA1 and exons 10 and 11 of BRCA2, We obtained a detailed family history o n all women we studied who had cancer and on a control population of 386 As hkenazi Jewish women without ovarian or breast cancer. A founder mutation w as present in 41.3% of the women we studied, The cumulative incidence of ov arian cancer to age 75 years was found to be 6.3% for female first-degree r elatives of the patients with ovarian cancer, compared with 2.0% for the fe male relatives of healthy controls (relative risk 3.2; 95% CI 1.5-6.8; P = .002). The relative risk to age 75 years for breast cancer among the female first-degree relatives was 2.0 (95% CI 1.4-3.0; P = .0001). Only one nonfo under mutation was identified (in this instance, in a woman of mixed ancest ry), and the three founding mutations accounted for most of the observed ex cess risk of ovarian and breast cancer in relatives.