Oral Contraceptives and the Risk of Hereditary Ovarian Cancer
Steven A. Narod, M.D., Harvey Risch, M.D., Ph.D., Roxana Moslehi, M.Sc., Anne Dørum, M.D., Susan Neuhausen, Ph.D., Hakan Olsson, M.D., Diane Provencher, M.D., Paolo Radice, Ph.D., Gareth Evans, M.D., Susan Bishop, M.Sc., Jean-Sébastien Brunet, M.Sc., Bruce A.J. Ponder, M.D., Ph.D., Jan G.M. Klijn, M.D., for The Hereditary Ovarian Cancer Clinical Study Group
Background Women with mutations in either the BRCA1 or the BRCA2gene have a high lifetime risk of ovarian cancer. Oral contraceptivesprotect against ovarian cancer in general, but it is not knownwhether they also protect against hereditary forms of ovariancancer.
Methods We enrolled 207 women with hereditary ovarian cancerand 161 of their sisters as controls in a case–controlstudy. All the patients carried a pathogenic mutation in eitherBRCA1 (179 women) or BRCA2 (28 women). The control women wereenrolled regardless of whether or not they had either mutation.Lifetime histories of oral-contraceptive use were obtained byinterview or by written questionnaire and were compared betweenpatients and control women, after adjustment for year of birthand parity.
Results The adjusted odds ratio for ovarian cancer associatedwith any past use of oral contraceptives was 0.5 (95 percentconfidence interval, 0.3 to 0.8). The risk decreased with increasingduration of use (P for trend, <0.001); use for six or moreyears was associated with a 60 percent reduction in risk. Oral-contraceptiveuse protected against ovarian cancer both for carriers of theBRCA1 mutation (odds ratio, 0.5; 95 percent confidence interval,0.3 to 0.9) and for carriers of the BRCA2 mutation (odds ratio,0.4; 95 percent confidence interval, 0.2 to 1.1).
Conclusions Oral-contraceptive use may reduce the risk of ovariancancer in women with pathogenic mutations in the BRCA1 or BRCA2gene.
Source Information
From the Centre for Research on Women's Health, Women's College Hospital, University of Toronto, Toronto (S.A.N., S.B., J.-S.B.); the Department of Epidemiology and Public Health, Yale University, New Haven, Conn. (H.R.); the Department of Medical Genetics, University of British Columbia, Vancouver, Canada (R.M.); the Unit of Medical Genetics, Norwegian Radium Hospital, Oslo, Norway (A.D.); the Department of Medical Informatics, University of Utah, Salt Lake City (S.N.); the Department of Oncology, Lund University, Lund, Sweden (H.O.); the Department of Obstetrics and Gynecology, Notre Dame Hospital, Montreal (D.P.); the Istituto Nazionale Tumori, Milan, Italy (P.R.); the Department of Medical Genetics, St. Mary's Hospital, Manchester, United Kingdom (G.E.); and the Cancer Research Campaign Genetic Epidemiology Unit, Cambridge University, Cambridge, United Kingdom (B.A.J.P.). Jan G.M. Klijn, M.D. (Department of Medical Oncology, Rotterdam Cancer Institute, Rotterdam, the Netherlands), was also an author.
Address reprint requests to Dr. Narod at the Centre for Research on Women's Health, Women's College Hospital, 790 Bay St., Rm. 750a, Toronto, ON M5G 1N8, Canada.
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