Ovarian cancer risk factor associations by primary anatomic site: The ovarian cancer cohort consortium

Renee T. Fortner, Megan S. Rice, Synnove F. Knutsen, Michael J. Orlich, Kala Visvanathan, Alpa V. Patel, Mia M. Gaudet, Anne Tjønneland, Marina Kvaskoff, Rudolf Kaaks, Antonia Trichopolou, Valeria Pala, N. Charlotte Onland-Moret, Inger T. Gram, Pilar Amiano, Annika Idahl, Naomi E. Allen, Elisabete Weiderpass, Jenny N. Poynter, Kim RobienGraham G. Giles, Roger L. Milne, Veronica W. Setiawan, Melissa A. Merritt, Piet A. Van Den Brandt, Anne Zeleniuch-Jacquotte, Alan A. Arslan, Katie M. O'Brien, Dale P. Sandler, Alicja Wolk, Niclas Hakansson, Holly R. Harris, Britton Trabert, Nicolas Wentzensen, Shelley S. Tworoger, Leo J. Schouten

Research output: Contribution to journalArticlepeer-review


Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. Results: Most associations did not vary by tumor site (Phet ≥ 0.05). Associations between first pregnancy (Phet ¼ 0.04), tubal ligation (Phet ¼ 0.01), and early-adult (age 18–21 years) body mass index (BMI; Phet ¼ 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (Phet ¼ 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

Original languageEnglish (US)
Pages (from-to)2010-2018
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Issue number10
StatePublished - Oct 1 2020

Bibliographical note

Funding Information:
Supported by Department of Defense Ovarian Cancer Research Program grant W81XWH-12-1-0561 (PI: to S.S. Tworger). Also supported by K05 CA154337 from the NCI and Office of Dietary Supplements [VITAL (Vitamins and Lifestyle study cohort)]; R01 CA39742 (Iowa Women's Health Study); CA164973 (Multiethnic Cohort); UM1 CA186107, P01 CA87969, UM1 CA176726, and R01 CA67262 (Nurses? Health Study, Nurses? Health Study II); NIH UM1 CA182934 and center grants P30 CA016087 and P30 ES000260 (NYU Women's Health Study); grants from the Swedish Research Council (Swedish Mammography Cohort). All aspects of the Cancer Prevention Study II were funded by the Intramural Research Program of the American Cancer Society and by the NCI Intramural Research Program, Intramural Research Program of the NIH, and National Institute of Environmental Health Sciences. The Sister Study is funded by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences project Z01-ES044005. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l?Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM; France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF; Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Nordforsk (Norway); Health Research Fund (FIS), PI13/00061 to Granada; PI13/01162 to EPIC-Murcia), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020; Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Ska ne and V?asterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford; United Kingdom). Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414, and 1074383 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database.

Publisher Copyright:
© 2020 American Association for Cancer Research.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.


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