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No Association of the I1307K APC Allele with Ovarian Cancer Risk in Ashkenazi Jews¹

Women's College Hospital, The Centre for Research in Women's Health, Toronto, Ontario, M5G 1N8 Canada [J. A., R. M., D. V., J-S. B., S. A. N.]; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6H 3N1 Canada [R. M.]; Department of Obstetrics/Gynecology, Cedars Sinai Medical Center, Los Angeles, California 90048 [B. K.]; Department of Gynecologic Oncology, Prentice Women's Hospital, Chicago, Illinois 60611 [D. F.]; Department of Obstetrics and Gynecology, Long Island Jewish Hospital, New Hyde Park, New York 11040 [D. S.]; Department of Gynecologic Oncology, Central Emek Hospital, Haifa, Israel [Y. B. D.]; Institute of Oncology, Kaplan Hospital, Rehovot, Israel [H. B.]; and Division of Gynecologic Oncology, Albert Einstein College of Medicine, Bronx, New York 10461 [A. F.]

Familial adenomatous polyposis is a dominantly inherited colon cancer syndrome associated with germ-line mutations in the APC tumor suppressor gene. An APC gene sequence alteration, the 11307K allele, 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 11307K variant and measured the effect of this allele on the risk for cancer development in their first-degree relatives. We identified the I1307K allele in 7.9% (15 of 190) of our ovarian cancer cases. The average age of ovarian cancer diagnosis in carriers of the I1307K allele (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 I1307K allele (3.0%) had a history of colorectal cancer versus 20 of 987 relatives of probands without the I1307K allele (2.1%; relative risk, 1.48; 95% confidence interval, 0.45–4.88; P = 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 allele (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 allele is unlikely to increase the risk of ovarian cancer or of cancer in general.

¹ This study was supported by NIH Grant IRO1 CA63678 and Department of the Army Grant DAMD 17-94-J-4299.

² To whom requests for reprints should be addressed, at Center for Research in Women's Health, 790 Bay Street, Suite 750A, 7th Floor, Toronto, Ontario, M5G 1N8 Canada.

Received 3/24/98. Accepted 6/ 1/98.

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