RISKS OF CANCER IN BRCA1-MUTATION CARRIERS

Germline mutations in a gene on chromosome 17q known as BRCA1 are responsible for a large proportion of inherited predispositions to breast and ovarian cancer. In 33 families with evidence of linkage to BRCA1, we estimated the risks of breast and ovarian cancer from the occurrence of second cancers in individuals with breast cancer, and examined the risks of other cancers in BRCA1 carriers. 26 contralateral primary breast cancers occurring more than 3 years after a first breast cancer were observed before age 70, giving an estimated cumulative risk of breast cancer in gene carriers of 87% by age 70. 23 primary ovarian cancers occurred in women with a previous breast cancer, resulting in an estimated cumulative risk of ovarian cancer of 44% by age 70. 87 cancers other than breast or ovarian cancer were observed in individuals with breast or ovarian cancer and their first-degree relatives compared with 69.3 expected, based on national incidence rates. Significant excesses were observed for colon cancer (estimated relative risk [RR] to gene carriers 4.11 [95% Cl 2.36-7.15]) and prostate cancer(3.33 [1.78-6.20]). No significant excesses (or deficits) were noted for cancers of other sites. Our study provides estimates of breast and ovarian cancer risks which are useful for counselling BRCA1-mutation carriers. It also shows that carriers are at increased risk of colon and prostate cancer, which may be of clinical significance in certain families if the risks are associated with specific mutations.