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.
Bibliographical noteFunding Information:
Alberta Heritage Foundation for Medical Research; Associazione Italiana per la Ricerca sul Cancro; California Department of Public Health; Canadian Breast Cancer Research Alliance; Canadian Cancer Society; Canadian Institutes of Health Research; Cancer Council Tasmania, Grant/Award Numbers: 403031, 457636; Centers for Disease Control and Prevention's National Program of Cancer Registries; Health and Welfare Canada; Intramural Research Program of the National Cancer Institute/National Institutes of Health, Department of Health and Human Services, United States; Italian League Against Cancer; KWF Kankerbestrijding; le Ministère de la Santé et des Services Soçiaux du Québec; Nova Scotia Department of Health; Manitoba Health Services Commission; Medical Research Council Canada; Memorial Sloan Kettering NCI Support Grant, Grant/Award Number: P30 CA008748; National Cancer Institute, Grant/Award Numbers: 2R01 CA082838, P01 CA87969, CA11535, N01‐CN‐05223, N01‐CN‐55424, P01‐CA77596, P30CA016056, P30CA118100, R01 CA081212, U01 CA182934, P30 CA016087, R01 CA083918, R01 CA092585, R01 CA39742, R01 CA48774, P30 CA14089, R01 CA058420, U01 CA164974, R03 CA169888, R01 CA098346, R01 CA77398, R35 CA39779, R01 CA47749, R01 CA75977, N01 HD 2 31, U01 CA164973, RO3 CA135632; National Cancer Institute of Canada; National Health and Medical Research Council, Grant/Award Numbers: APP339435, APP1073898, APP1061341, APP1061779, ID 1061778, GNT 1073898; National Institutes of Health, Grant/Award Number: R01 CA74877; Ontario Ministry of Health; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Grant/Award Number: 32.9495.88; Krebsforschung Schweiz Stiftung, Grant/Award Number: OCS 1633‐02‐2005; U.S. Public Health Service, Grant/Award Numbers: P01‐CA‐33619, R01‐CA‐58598, R01‐CA‐55700, P20‐CA‐57113; Vetenskapsrådet, Grant/Award Number: 521‐2011‐2955 Funding information
L. S. Cook held a Canada Research Chair, received AHFMR career award funding and received support from NCI P30CA118100. M. Du and M. C. Pike were supported by the Memorial Sloan Kettering NCI Support Grant P30 CA008748. C. M. Friedenreich received career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research (AHFMR) during the conduct of this study. C. La Vecchia was supported by the Italian Foundation for Research in Cancer. A. B. Miller was supported in part by a National Health Scientist Award from Health and Welfare Canada. R. Na was supported by NHMRC Program Grant GNT 1073898. A. B. Spurdle was supported by a fellowship from the NHMRC (ID 1061778).
: This study was supported by funding from the Canadian Breast Cancer Research Alliance, the Canadian Cancer Society, Health and Welfare Canada, the National Cancer Institute of Canada, the Alberta Heritage Foundation for Medical Research, Manitoba Health Services Commission, Medical Research Council of Canada, le Ministre de la Santé et des Services Soçiaux du Québec, the Nova Scotia Department of Health, and the Ontario Ministry of Health. CNBSS è
: National Institutes of Health (R01CA77398) and the CBCRP fund; the collection of cancer incidence data was supported by the California Department of Public Health as part of the state wide cancer reporting program mandated by California Health and Safety Code Section 103885, the NCI's Surveillance, Epidemiology, and End Results Program awarded to the Cancer Prevention Institute of California, the Public Health Institute, University of Southern California, and the Centers for Disease Control and Prevention's National Program of Cancer Registries. CTS
: This investigation was supported in part by USPHS Grants P01‐CA‐33619, R01‐CA‐58598, R01‐CA‐55700, and P20‐CA‐57113 and by contracts N01‐CN‐05223 and N01‐CN‐55424 from the National Cancer Institute, NIH, Department of Health and Human Services. HAWAII
: Swiss National Science Foundation grant 32.9495.88 and the Krebsforschung Schweiz Stiftung grant OCS 1633‐02‐2005. VAUD
- endometrial cancer
- induced abortion
- sex of offspring