Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium.
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. r.fortner@dkfz-heidelberg.de lj.schouten@maastrichtuniversity.nl.
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.
- School of Public Health, Loma Linda University, Loma Linda, California.
- Johns Hopkins Bloomberg School of Public Health and School of Medicine, Baltimore, Maryland.
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
- CESP, Fac. de médecine-Univ. Paris-Sud, Fac. de médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Hellenic Health Foundation, Athens, Greece.
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
- Public Health División of Gipuzkoa, BioDonostia Research Institute, San-Sebastian-Donostia, Spain.
- Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
- International Agency for Research on Cancer, Lyon, France.
- Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, Minnesota.
- Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC.
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
- University of Southern California, Los Angeles, California.
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
- New York University School of Medicine, New York, New York.
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina.
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
- Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Washington, DC.
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands. r.fortner@dkfz-heidelberg.de lj.schouten@maastrichtuniversity.nl.
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 (P het ≥ 0.05). Associations between first pregnancy (P het = 0.04), tubal ligation (P het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P het = 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 (P het = 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.