Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
- Director's Office, International Agency for Research on Cancer, World Health Organization, Lyon, France.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
- School of Public Health, Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota, USA.
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
- Division of Epidemiology, Biostatistics & Preventive Medicine, Department of Internal Medicine, NM Health Sciences Center, University of New Mexico, University of New Mexico, Albuquerque, New Mexico, USA.
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
- Department of Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, Alberta, Canada.
- Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
- Cancer Prevention and Control Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
- Department of Epidemiology and Health Services Research, Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.
- Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA.
- Epidemiology Division, Dalla Lana School of Public Health, Toronto, Ontario, Canada.
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
- Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.
- Slone Epidemiology Center at Boston University, Boston, Massachusetts, USA.
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
- Screening, Prevention, Etiology and Cancer Survivorship Program, University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota, USA.
- Division of Population Science, Dana-Farber Cancer Institute and Harvard TH Chan School of Public Health, Boston, Massachusetts, USA.
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
- Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico IRCCS, Aviano, Italy.
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
- Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, Bethesda, Maryland, USA.
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
- Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
- Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
- Department of Epidemiology, Fudan University School of Public Health, Shanghai, China.
- Department of Population Health and Perlmutter Cancer Center, New York University Langone Health, New York, New York, USA.
A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.