Causal Relationship between Metabolic Syndrome and Breast Cancer: A Bidirectional Two-Sample Mendelian Randomization

Objective: To investigate the causal relationship between metabolic syndrome and breast cancer. Methods: GWAS data for metabolic syndrome and breast cancer were downloaded from the IEU GWAS database and the GWAS catalog database, respectively. A bidirectional design was employed, treating each as both exposure and outcome. Two-sample Mendelian randomization analysis was performed, using inverse variance weighted method as the primary approach, supplemented by MR-Egger regression, weighted median, simple mode, and weighted mode methods. Strong instrumental variables (F>10) were analyzed. Heterogeneity analysis, horizontal pleiotropy analysis, forest plots, and leave-one-out validation were used to assess the reliability of the results. Results: IVW analysis showed no causal relationship between metabolic syndrome and breast cancer OR=1.00, 95%CI (0.97-1.03), P>0.05. Sensitivity analyses confirmed the robustness of the findings. Conclusion: This study found no evidence to support a positive causal relationship between metabolic syndrome and breast cancer, nor did it support a reverse causal relationship between breast cancer and metabolic syndrome.