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Int J Cancer. 2019 Jun 7. doi: 10.1002/ijc.32494. [Epub ahead of print]

Associations of pregnancy-related factors and birth characteristics with risk of endometrial cancer: A Nordic population-based case-control study.

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Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Cancer Registry of Norway, Oslo, Norway.
Department of Medicine, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Information Services Department, National Institute for Health and Welfare (THL), Helsinki, Finland.
Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Cancer Society of Finland, Finnish Cancer Registry, Helsinki, Finland.
Department of Pediatrics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.


Many pregnancy-related factors are associated with reduced endometrial cancer risk. However, it remains unclear whether pregnancy-related complications (e.g., hypertensive conditions) are associated with risk and whether these associations vary by endometrial cancer subtype. Thus, we evaluated the risk of endometrial cancer, overall and by subtype, in relation to pregnancy-related factors, pregnancy complications and birth characteristics. Utilizing population-based register data from four Nordic countries, we conducted a nested case-control analysis of endometrial cancer risk. We included 10,924 endometrial cancer cases and up to 10 matched controls per case. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models. We further evaluated associations by individual histology (i.e., endometrioid, serous, etc.) or, for rare exposures (e.g., pregnancy complications), by dualistic type (Type I [n = 10,343] and Type II [n = 581]). Preexisting and pregnancy-related hypertensive conditions were associated with increased endometrial cancer risk (OR [95% CI]: preexisting hypertension 1.88 [1.39-2.55]; gestational hypertension 1.47 [1.33-1.63]; preeclampsia 1.43 [1.30-1.58]), with consistent associations across dualistic type. Increasing number of pregnancies (≥4 vs. 1 birth: 0.64 [0.59-0.69]) and shorter time since last birth (<10 vs. ≥30 years: 0.34 [0.29-0.40]) were associated with reduced endometrial cancer risk, with consistent associations across most subtypes. Our findings support the role for both hormonal exposures and cell clearance as well as immunologic/inflammatory etiologies for endometrial cancer. This research supports studying endometrial hyperplasia, a precursor condition of endometrial cancer, in the context of pregnancy-related exposures, as this may provide insight into the mechanisms by which pregnancy affects subsequent cancer risk.


Nordic countries; endometrial cancer; hypertension; preeclampsia; pregnancy timing


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