Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies

Alice W. Lee & P. M. Webb et al.

Abstract

Background

Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated.

Methods

A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses.

Results

Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend < .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer.

Conclusions

Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

Funding
Project 1Epidemiology of Ovarian Cancer:New HypothesesCancer Center AdministrationNorthern California Cooperative Family Registry for Breast CancerMedical Research Council Grant MC_UU_12023/20Hereditary Breast Cancer: Genetic and Molecular StudiesDNA POLYMORPHISMS IN OVARIAN CANCER--CASE CONTROL STUDYDana-Farber/Harvard Cancer Center Ovarian Cancer SPOREMedical Research Council Grant MC_UU_00004/01The Molecular Epidemiology Of Ovarian CancerRelating Molecular Subgroups of Endometriosis-Associated Ovarian Cancers to Survival and RiskFollow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)SURVEILLANCE EPIDEMIOLOGY AND END RESULTSProject 2: Next Generation TOP1 Inhibition for the Treatment of Ovarian CancerCancer Research UK Grant 16561University of Michigan Training Program in Genomic ScienceCASE CONTROL STUDY OF OVARIAN CANCER HORMONAL ETIOLOGYPathologyPCOS, Type II diabetes and ovarian cancer riskOvarian Cancer Research Fund FundingKathryn Sladek Smith Grant PPD/RPCI.07US National Cancer Institute at the National Institutes of Health Grant GAME-ON Post-GWASFollow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)US Army Medical Research and Materiel Command Grant DAMD17-01–1-0729The Cancer Council Tasmania and The Cancer Foundation of Western Australia FundingNational Health and Medical Research Council of Australia Grant ID199600National Health and Medical Research Council of Australia Grant ID400413National Health and Medical Research Council of Australia Grant ID400281RISK FACTOR ANALYSIS OF BRCA1 AND BRCA2 CARRIERSCASE CONTROL STUDY OF OVARIAN CANCER HORMONAL ETIOLOGYDNA POLYMORPHISMS IN OVARIAN CANCER--CASE CONTROL STUDYSteroid Hormone Genes and Ovarian Cancer RiskNational Institutes of Health (NIH) Grant R01-CA87538PCOS, Type II diabetes and ovarian cancer riskGerman Federal Ministry of Education and Research FundingProgramme of Clinical Biomedical Research Grant 01 GB 9401German Cancer Research Center FundingNational Institutes of Health Grant R01-CA58598In vitro and In Vivo screening of chemopreventive agentsCancer Genetic Network (CGN)Department of Defense Grant DAMD17-02–1-0669OVARIAN CANCER RISK AND SURVIVAL IN BRCA CARRIERSNational Cancer Institute at the National Institutes of Health Grant R01-CA95023National Cancer Institute at the National Institutes of Health Grant P50-CA159981MALNational Cancer Institute at the National Institutes for Health Grant R01- CA61107Danish Cancer Society Grant 94 222 52Mermaid I FundingNIH Grant R01-CA76016Department of Defense Grant DAMD17-02–1-0666NIH Grant R01-CA54419Dana-Farber/Harvard Cancer Center Ovarian Cancer SPOREDepartment of Defense Grant W81XWH-10–1-02802National Cancer Institute at the National Institutes for Health Grant NIH-K07 CA095666National Cancer Institute at the National Institutes for Health Grant R01-CA83918National Cancer Institute at the National Institutes for Health Grant NIH-K22-CA138563Cancer Center AdministrationCancer Institute of New Jersey FundingIntramural Research Program of the National Cancer Institute FundingNational Institutes of Health Grant U01 CA71966National Institutes of Health Grant U01 CA69417Hereditary Breast Cancer: Genetic and Molecular StudiesLon V Smith Foundation Grant LVS-39420The Eve Appeal FundingNational Institute for Health Research University College London Hospitals Biomedical Research Centre FundingMRC core funding Grant MR_UU_12023NIH Grant P01CA17054NIH Grant P30CA14089NIH Grant R01CA61132NIH Grant N01PC67010The Progesterone Receptor Gene and Ovarian Cancer RiskOvarian Cancer and Gonadotropin SignalingSURVEILLANCE EPIDEMIOLOGY AND END RESULTSCalifornia Cancer Research Program Grant 00–01389 V-20170California Cancer Research Program Grant 2II0200PathologyMemorial Sloan-Kettering Cancer Center FundingScientific Scholar Award from the Rivkin Center for Ovarian Cancer Funding

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