RISKS OF CANCER IN BRCA1-MUTATION CARRIERS

Germline mutations in a gene on chromosome 17q known as BRCA1 are resp onsible 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 occurrenc e of second cancers in individuals with breast cancer, and examined th e risks of other cancers in BRCA1 carriers. 26 contralateral primary b reast cancers occurring more than 3 years after a first breast cancer were observed before age 70, giving an estimated cumulative risk of br east cancer in gene carriers of 87% by age 70. 23 primary ovarian canc ers occurred in women with a previous breast cancer, resulting in an e stimated cumulative risk of ovarian cancer of 44% by age 70. 87 cancer s other than breast or ovarian cancer were observed in individuals wit h breast or ovarian cancer and their first-degree relatives compared w ith 69.3 expected, based on national incidence rates. Significant exce sses were observed for colon cancer (estimated relative risk [RR] to g ene 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 cance r risks which are useful for counselling BRCA1-mutation carriers. It a lso shows that carriers are at increased risk of colon and prostate ca ncer, which may be of clinical significance in certain families if the risks are associated with specific mutations.