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
Background Multiparity and the use of oral contraceptives reducethe risk of ovarian cancer, but their effects on this risk inwomen with a BRCA1 or BRCA2 mutation are unclear.
Methods We conducted a population-based casecontrol studyof ovarian cancer among Jewish women in Israel. Women were testedfor the two founder mutations in BRCA1 and the one founder mutationin BRCA2 that are known to be common among Jews. We estimatedthe effects of parity and oral-contraceptive use on the riskof ovarian cancer in carriers and noncarriers in separate analysesthat 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 of840 women with ovarian cancer (29.0 percent) had a BRCA1 orBRCA2 mutation. Overall, each additional birth and each additionalyear of use of oral contraceptives were found to lower the riskof ovarian cancer, as expected. Additional births were protectivein separate analyses of carriers and noncarriers, but oral-contraceptiveuse appeared to reduce the risk only in noncarriers; among carriers,the reduction in the odds of ovarian cancer was 12 percent perbirth (95 percent confidence interval, 2.3 to 21 percent) and0.2 percent per year of oral-contraceptive use (4.9 to5.0 percent).
Conclusions The risk of ovarian cancer among carriers of a BRCA1or BRCA2 mutation decreases with each birth but not with increasedduration of use of oral contraceptives. These data suggest thatit is premature to use oral contraceptives for the chemopreventionof 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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