CANCER RISKS IN 2 LARGE BREAST-CANCER FAMILIES LINKED TO BRCA2 ON CHROMOSOME 13Q12-13

The penetrance of the BRCA2 gene on chromosome 13q12-13 has been estim ated in two large, systematically ascertained, linked families, by use of a maximum-likelihood method to incorporate both cancer-incidence d ata and 13q marker typings in the families. The cumulative risk of bre ast cancer in female gene carriers was estimated to be 59.8% by age 50 years (95% confidence interval [95%CI] 25.9%-78.5%) and 79.5% by age 70 years (95%CI 28.9%-97.5%). The cumulative risk of breast cancer in male carriers was estimated to be 6.3% (35%CI 1.4%-25.6%) by age 70 ye ars. There was no evidence of any risk difference between the two fami lies. These results indicate that the lifetime breast cancer risk in B RCA2 carriers, for at least a subset of mutations, is comparable to th at for BRCA1. A significant excess of ovarian cancer in gene carriers was observed (relative risk 17.69, based on three cases), but the abso lute risk of ovarian cancer was less than that reported for BRCA1. Sig nificant excesses of laryngeal cancer (relative risk 7.67, based on tw o possible carriers) and prostate cancer (relative risk 2.89, based on five possible carriers) were also observed. One case of ocular melano ma, as well as a second eye cancer of unspecified histology, occurred in obligate gene carriers.