No Association of the I1307K APC Alíelewith Ovarian Cancer Risk in

Familial adenomatous polyposis is a dominantly inherited colon cancer syndrome associated with germ-line mutations in the APC tumor suppres sor gene. An APC gene sequence alteration, the I1307K alA­ele,occurs in 6% of the Ashkenazi Jewish population and is reported to double the risk for colorectal cancer. We screened a population of 190 Ashkenazi women who were diagnosed with epithelial ovarian carcinoma for the I1307K variant and measured the effect of this alA­eleon the risk for cancer development in their first-degree relatives. We identified the I1307K alA­ele in 7.9% (15 of 190) of our ovarian cancer cases. The average age of ovarian cancer diagnosis in carriers of the I1307K alA­ele(57.5 years) was not statistically different than the age for noncarriers (56.4 years; P = 0.70). Among the 1087 first-degree relatives, there were 23 cases of colorectal cancer; 3 of 100 relatives of probands with the II307K alA­ele (3.0%) had a history of colorectal cancer versus 20 of 987 relatives of probands without the 11307K alA­ele(2.1%; relative risk, 1.48; 95% con fidence interval, 0.45-4.88; /' = 0.462). Relatives of the I1307K carriers had a risk of 38.0% for developing any cancer to age 80, similar to the risk for relatives of noncarriers of the I1307K alA­ele(42.1 %; P = 0.86). The average age of diagnosis of cancer of any type was not different between relatives of carriers (59.0 years) and noncarriers (60.4 years). In the Ashkenazi Jewish population, the I1307K alA­eleis unlikely to increase the risk of ovarian cancer or of cancer in general.