Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Joanne Kotsopoulos, Jan Lubinski, Jacek Gronwald, Cezary Cybulski, Rochelle Demsky, Susan L Neuhausen, Charmaine Kim-Sing, Nadine Tung, Susan Friedman, Leigha Senter, Jeffrey Weitzel, Beth Karlan, Pal Moller, Ping Sun, Steven A Narod, Henry T Lynch (Collaborator), Christian Singer (Collaborator), Charis Eng (Collaborator), Gillian Mitchell (Collaborator), Tomasz Huzarski (Collaborator)Jeanna McCuaig (Collaborator), Kevin Hughes (Collaborator), Gordon Mills (Collaborator), Parviz Ghadirian (Collaborator), Andrea Eisen (Collaborator), Dawna Gilchrist (Collaborator), Joanne L Blum (Collaborator), Dana Zakalik (Collaborator), Tuya Pal (Collaborator), Mary Daly (Collaborator), Barbara Weber (Collaborator), Carrie Snyder (Collaborator), Taya Fallen (Collaborator), Albert Chudley (Collaborator), John Lunn (Collaborator), Talia Donenberg (Collaborator), Raluca N Kurz (Collaborator), Howard Saal (Collaborator), Judy Garber (Collaborator), Gad Rennert (Collaborator), Kevin Sweet (Collaborator), Ruth Gershoni-Baruch (Collaborator), Christine Rappaport (Collaborator), Edmond Lemire (Collaborator), Dominique Stoppa-Lyonnet (Collaborator), Olufunmilayo I Olopade (Collaborator), Sofia Merajver (Collaborator), Louise Bordeleau (Collaborator), Carey A Cullinane (Collaborator), Eitan Friedman (Collaborator), Wendy McKinnon (Collaborator), Marie Wood (Collaborator), Daniel Rayson (Collaborator), Wendy Meschino (Collaborator), Jane McLennan (Collaborator), Josephine Wagner Costalas (Collaborator), Robert E Reilly (Collaborator), Susan Vadaparampil (Collaborator), Kenneth Offit (Collaborator), Noah Kauff (Collaborator), Jan Klijn (Collaborator), David Euhus (Collaborator), Ava Kwong (Collaborator), Claudine Isaacs (Collaborator), Fergus Couch (Collaborator), Siranoush Manoukian (Collaborator), Tomasz Byrski (Collaborator), Christine Elser (Collaborator), Seema Panchal (Collaborator), Susan Armel (Collaborator), Sonia Nanda (Collaborator), Kelly Metcalfe (Collaborator), Aletta Poll (Collaborator), Barry Rosen (Collaborator), William D Foulkes (Collaborator), Timothy Rebbeck (Collaborator), Peter Ainsworth (Collaborator), Andre Robidoux (Collaborator), Ellen Warner (Collaborator), Lovise Maehle (Collaborator), Michael Osborne (Collaborator), Gareth Evans (Collaborator), Barbara Pasini (Collaborator), Ophira Ginsburg (Collaborator), Stephanie Cohen (Collaborator), Gorski Bohdan (Collaborator), Anna Jakubowska (Collaborator), Janice Little (Collaborator)

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41-0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79-0.96; p-trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03-1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.
    Original languageEnglish
    JournalInternational journal of cancer. Journal international du cancer
    Volume137
    Issue number5
    DOIs
    Publication statusPublished - 1 Sep 2015

    Keywords

    • BRCA1
    • BRCA2
    • ovarian cancer
    • ovulation

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