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About this Publication
Title
Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.
Pubmed ID
33105052 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Int J Cancer. 2021 May 1; Volume 148 (Issue 9): Pages 2068-2078
Authors
Jordan SJ, Na R, Weiderpass E, Adami HO, Anderson KE, van den Brandt PA, Brinton LA, Chen C, Cook LS, Doherty JA, Du M, Friedenreich CM, Gierach GL, Goodman MT, Krogh V, Levi F, Lu L, Miller AB, McCann SE, Moysich KB, ...show more Negri E, Olson SH, Petruzella S, Palmer JR, Parazzini F, Pike MC, Prizment AE, Rebbeck TR, Reynolds P, Ricceri F, Risch HA, Rohan TE, Sacerdote C, Schouten LJ, Serraino D, Setiawan VW, Shu XO, Sponholtz TR, Spurdle AB, Stolzenberg-Solomon RZ, Trabert B, Wentzensen N, Wilkens LR, Wise LA, Yu H, La Vecchia C, De Vivo I, Xu W, Zeleniuch-Jacquotte A, Webb PM
Affiliations
  • 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.
...show more
  • 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.
Abstract

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.

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