Offspring sex and risk of epithelial ovarian cancer: a multinational pooled analysis of 12 case–control studies
While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. We performed a pooled analysis among parous participants from 12 case-controls studies comprising 6872 EOC patients and 9101 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression for case-control associations and polytomous logistic regression for histotype-specific associations, all adjusted for potential confounders. In general, no associations were found between offspring sex and EOC risk. However, compared to bearing only female offspring, bearing one or more male offspring was associated with increased risk of mucinous EOC (OR = 1.45; 95% CI = 1.01-2.07), which appeared to be limited to women reporting menarche before age 13 compared to later menarche (OR = 1.71 vs 0.99; P-interaction = 0.02). Bearing increasing numbers of male offspring was associated with greater risks of mucinous tumors (OR = 1.31, 1.84, 2.31, for 1, 2 and 3 or more male offspring, respectively; trend-p = 0.005). Stratifying by hormonally-associated conditions suggested that compared to bearing all female offspring, bearing a male offspring was associated with lower risk of endometrioid cancer among women with a history of adult acne, hirsutism, or polycystic ovary syndrome (OR = 0.49, 95% CI = 0.28-0.83) but with higher risk among women without any of those conditions (OR = 1.64 95% CI = 1.14-2.34; P-interaction = 0.003). Offspring sex influences the childbearing-EOC risk relationship for specific histotypes and conditions. These findings support the differing etiologic origins of EOC histotypes and highlight the importance of EOC histotype-specific epidemiologic studies. These findings also suggest the need to better understand how pregnancy affects EOC risk.
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Hormones, DNA Repair, BRCA1/2 and Ovarian Cancer Preven*Cancer Council NSW Grant 191. 211 and 182SURVEILLANCE EPIDEMIOLOGY & END RESULTS PROGRAMOvarian Cancer Research Fund Grant PPD/RPCI.07Medical Research Council Grant MC_UU_12023/20Obesity in ovarian cancer prognosisDNA POLYMORPHISMS IN OVARIAN CANCER--CASE CONTROL STUDYCASE CONTROL STUDY OF OVARIAN CANCER HORMONAL ETIOLOGYRISK FACTOR ANALYSIS OF BRCA1 AND BRCA2 CARRIERSOVARIAN CANCER RISK AND SURVIVAL IN BRCA CARRIERSNIH HHS Grant R01-CA58598, N01-CN-55424 and N01-PC-67001NIH HHS Grant P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148, R03CA115195, N01CN025403,National Health Research and Development Program, Health Canada Grant 6613-1415-53The Molecular Epidemiology Of Ovarian CancerThe Role of Prolactin in Postmenopausal Breast CancerGENETIC/EPIDEMIOLOGY STUDY OF EPITHELIAL OVARIAN TUMORSPhytoestrogens, alcohol, and endometrial cancer riskPeter MacCallum Cancer Centre Grant AOCSRegulatory T Cell Function in Ovarian CancerNIH HHS Grant R01-CA074850; R01-CA080742NCI NIH HHS Grant K07-CA080668,R01-CA95023, MO1-RR000056 R01-CA126841Population-Based Analysis of Ovarian Cancer BiomarkersCalifornia Cancer Research Program Grant 00-01389V-20170, 2II0200General Clinical Research CenterCancer Center AdministrationInflammation and Ovarian CancerNational Health & Medical Research Council of Australia Grant 199600, 400413 and 105 400281Serum Markers of Breast /Ovarian Cancer RiskThe Progesterone Receptor Gene and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskMRF Grant MR_UU_12023NCI NIH HHS Grant NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, P30CA072720NIH HHS Grant R01 CA063678 and R01 CA063682German Federal Ministry of Education and Research Grant 01 GB 9401Cancer Research Training and Education CoordinationESTROGEN, DIET, GENETICS AND ENDOMETRIAL CANCEROvarian Cancer and Gonadotropin SignalingPlanning Grant for a Study of the Effect of Radiation o*DOD Peer Reviewed Cancer Research Program Grant DAMD17-02-1-0669Division of Cancer Epidemiology and Genetics, National Cancer Institute Grant R01-CA074850; R01-CA080742);Medical Research and Materiel Command Grant DAMD17-01-1- 104 0729Hormone Therapy and Risk of Ovarian CancerOvarian Cancer: Prevention and Its RecurrenceSURVEILLANCE EPIDEMIOLOGY AND END RESULTSNIH HHS Grant R01-CA76016NIH HHS Grant R01-CA106414-A2American Cancer Society Grant CRTG-00-196-01-CCEDOD Peer Reviewed Cancer Research Program Grant DAMD17-98-1-8659