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Original Article
Volume 345:235-240 July 26, 2001 Number 4
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Parity, Oral Contraceptives, and the Risk of Ovarian Cancer among Carriers and Noncarriers of a BRCA1 or BRCA2 Mutation
Baruch Modan, M.D., Patricia Hartge, Sc.D., Galit Hirsh-Yechezkel, M.Sc., Angela Chetrit, M.Sc., Flora Lubin, M.Sc., Uzi Beller, M.D., Gilad Ben-Baruch, M.D., Amiram Fishman, M.D., Joseph Menczer, M.D., Jeffery P. Struewing, M.D., Margaret A. Tucker, M.D., Sara M. Ebbers, B.S., Eitan Friedman, M.D., Benjamin Piura, M.D., Sholom Wacholder, Ph.D., for the National Israel Ovarian Cancer Study Group

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ABSTRACT

Background Multiparity and the use of oral contraceptives reduce the risk of ovarian cancer, but their effects on this risk in women with a BRCA1 or BRCA2 mutation are unclear.

Methods We conducted a population-based case–control study of ovarian cancer among Jewish women in Israel. Women were tested for the two founder mutations in BRCA1 and the one founder mutation in BRCA2 that are known to be common among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate analyses that included all control women, who did not have ovarian cancer.

Results Of 751 controls who underwent mutation analysis, 13 (1.7 percent) had a BRCA1 or BRCA2 mutation, whereas 244 of 840 women with ovarian cancer (29.0 percent) had a BRCA1 or BRCA2 mutation. Overall, each additional birth and each additional year of use of oral contraceptives were found to lower the risk of ovarian cancer, as expected. Additional births were protective in separate analyses of carriers and noncarriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the reduction in the odds of ovarian cancer was 12 percent per birth (95 percent confidence interval, 2.3 to 21 percent) and 0.2 percent per year of oral-contraceptive use (–4.9 to 5.0 percent).

Conclusions The risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral contraceptives for the chemoprevention of ovarian cancer in carriers of such mutations.


Source Information

From the Chaim Sheba Medical Center, Tel-Hashomer, Israel (B.M., G.H.-Y., A.C., F.L., G.B.-B.); the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md. (P.H., J.P.S., M.A.T., S.W.); the Shaare Zedek Medical Center, Jerusalem, Israel (U.B.); the Sapir Medical Center, Kfar Saba, Israel (A.F.); and the Edith Wolfson Medical Center, Holon, Israel (J.M.).

Other authors were Sara M. Ebbers, B.S. (Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md.), Eitan Friedman, M.D. (Chaim Sheba Medical Center, Tel-Hashomer, Israel), and Benjamin Piura, M.D. (Soroka Medical Center, Beer Sheba, Israel).

Address reprint requests to Dr. Modan at the Department of Clinical Epidemiology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel, or at BModan{at}gertner.health.gov.il.

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