Risk factors of ovarian cancer: a systematic review and meta-analysis of Mendelian randomiation studies

Abstract

Background: Ovarian cancer (OC) remains a major global health issue, often diagnosed late and lacking effective screening. Methods: MR studies until 11 September 2023 were identified by a systematic search across nine databases. We complied with PRISMA guidelines and included different OC subtypes and all exposures studied, conducting meta-analyses where feasible to combine estimates from non-overlapping samples. Results: We identified 120 articles examining genetic evidence for an association between 230 exposures and OC risk. Endometriosis, late age at menopause, and several adiposity measures were robustly associated with greater OC risk. In contrast, late age at menarche, higher adiponectin, and body fat without adverse metabolic profile were associated with lower risk (favourable adiposity: meta-analysis OR per SD 0.35, 95% CI 0.20–0.61). Meta-analyses on lipid-lowering drug target HMG-CoA reductase inhibitor (OR 0.66, 95% CI 0.53–0.82), serum vitamin D (OR 0.88, 95% CI 0.82–0.95), and dried fruit intake (HR 0.61, 95% CI 0.41–0.91) were supportive of protective associations. Conclusions: Genetic evidence confirms OC risks associated with endometriosis, and age at menarche and menopause. While greater overall adiposity increases the risk, fat without an adverse metabolic profile appears protective. Associations between vitamin D and HMG-CoA reductase inhibition with OC risk warrant further study.