Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer

We ascertained 184 Ashkenazi Jewish women with breast/ovarian cancer (171 b reast and 13 ovarian cancers, two of the former also had ovarian cancer) in a self-referral study. They were tested for germline founder mutations in BRCA1 (185delAG, 5382insC, 188de111) and BRCA2 (6174delT). Personal/family histories were correlated with mutation status. Logistic regression was use d to develop a model to predict those breast cancer cases likely to be germ line ERCA1/BRCA2 mutation carriers in this population. The most important f actors were age at diagnosis, personal/family history of ovarian cancer, or breast cancer diagnosed before 60 years in a first degree relative. A total of 15.8% of breast cancer cases, one of 13 ovarian cancer cases (7. 7%), and both cases with ovarian and breast cancer carried one of the found er mutations. Age at diagnosis in carriers (44.6 years) was significantly l ower than in non-carriers (52.1 years) (p<0.001), and was slightly lower in BRCA1 than BRCA2 carriers. Thirty three percent of carriers had no family history of breast or ovarian cancer in first or second degree relatives. Co nversely, 12% of non-mutation carriers had strong family histories, with bo th a first and a second degree relative diagnosed with breast or ovarian ca ncer. The predicted values from the logistic model can be used to define criteria for identifying Ashkenazi Jewish women with breast cancer who are at high risk of carrying BRCA1 and BRCA2 mutations. The following criteria would id entify those at approximately 10% risk: (1) breast cancer <50 years, (2) br east cancer <60 years with a first degree relative with breast cancer <60 y ears, or (3) breast cancer <70 years and a first or second degree relative with ovarian cancer.