Circulating Lipid Traits and Ovarian Cancer Risk: A Systematic Review and Meta-Analysis with Mendelian Randomization Integration

Background: Metabolic dysregulation is increasingly recognized as a contributor to carcinogenesis; however, the role of circulating lipid traits in ovarian cancer remains unclear. Methods: A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, and Embase were searched from inception to March 2026. Observational studies evaluating triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) in relation to ovarian cancer risk were included. Random-effects models were used to pool relative risks (RRs). Robustness was assessed via sensitivity analyses, influence diagnostics, and multiverse analysis. Mendelian randomization (MR) evidence was integrated for causal inference. Results: Six observational studies were included in the meta-analysis. Elevated triglyceride levels were associated with increased ovarian cancer risk, while HDL-C showed a modest inverse association. LDL-C and total cholesterol were not significantly associated with risk. Sensitivity analyses excluding early follow-up strengthened the triglyceride association. MR analyses supported a potential causal role for triglycerides but not for HDL-C. Conclusions: Circulating triglycerides may represent a metabolically relevant risk factor for ovarian cancer. Further large-scale prospective and mechanistic studies are warranted.