Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study

John R. McLaughlin, Harvey A. Risch, Jan Lubinski, Pal Moller, Parviz Ghadirian, Henry Lynch, Beth Karlan, David Fishman, Barry Rosen, Susan L. Neuhausen, Kenneth Offit, Noah Kauff, Susan Domchek, Nadine Tung, Eitan Friedman, William Foulkes, Ping Sun, Steven A. Narod

Research output: Contribution to journalArticlepeer-review

192 Scopus citations

Abstract

Background: Several of the known risk factors for ovarian cancer are thought to act through their effects on ovulation and the menstrual cycle, such as parity, breastfeeding, and use of oral contraceptives. We aimed to assess the effect of these three risk factors, and of tubal ligation, on the risk of ovarian cancer in women who carry a mutation in the BRCA1 or BRCA2 genes. Methods: We did a matched case-control study in women who were found to carry a pathogenetic mutation in BRCA1 or BRCA2. Participants were derived from a population-based study of ovarian cancer in Ontario, Canada, and from an international registry of mutation carriers based in Toronto, ON, Canada. All participants completed a written questionnaire that detailed their reproductive history. Women with invasive ovarian cancer and controls were matched on year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of breast cancer. The odds ratios and 95% CI for ovarian cancer were estimated with respect to use of oral contraceptives, parity, breastfeeding, and tubal ligation. Findings: Questionnaires were completed by 799 women with a history of invasive ovarian cancer (670 with BRCA1 mutations, 128 with BRCA2 mutations, and one with a mutation in both genes), and controls were 2424 women without ovarian cancer (2043 with BRCA1 mutations, 380 with BRCA2 mutations, and one with a mutation in both genes). Use of oral contraceptives reduced the risk of ovarian cancer in carriers of BRCA1 mutations (odds ratio 0·56 [95% CI 0·45-0·71]; p

Original languageEnglish (US)
Pages (from-to)26-34
Number of pages9
JournalLancet Oncology
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2007

All Science Journal Classification (ASJC) codes

  • Oncology

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