The Causal Association Between Blood Metabolites and Ovarian Cancer: Mendelian Randomization Study

Objective: Ovarian cancer is closely related to human metabolism, but the causal effect of serum metabolites on its occurrence and development is still unknown. Methods: Based on the publicly available Genome-Wide Association Studies (GWAS) abstract data set, this study used two-sample Mendelian randomization (MR) to determine the causal metabolites associated with ovarian cancer, and a comprehensive sensitivity analysis was used to verify the accuracy of the results. Finally, the metabolic pathway analysis of the causal metabolites that may affect the risk of ovarian cancer was carried out. Results: Based on the summary level of the GWAS data set, the MR method was first used to identify 17 metabolites that are highly correlated with the risk of ovarian cancer, 16 of which are related to ovarian cancer subtypes. Further sensitivity analysis excluded the influence of heterogeneity and horizontal pleiotropy, and confirmed the causal effects of 9 metabolites. Metabolic pathway analysis shows that tryptophan metabolic pathway may play a key role in invasive epithelial ovarian cancer, alanine, aspartic acid and glutamate metabolism, citrate cycle, glyoxylic acid and dicarboxylate Metabolism is closely related to mucinous ovarian cancer, and caffeine metabolism can affect the occurrence and development of low-grade potential ovarian cancer. Conclusion: This study comprehensively assessed the influence of blood metabolites on the risk of ovarian cancer and its different subtypes through genetic methods.