The causality between Type 2 diabetes and breast cancer: a bidirectional two-sample Mendelian randomization study

<b>Objective:</b> Observational studies showed that Type 2 diabetes increased the risk of breast cancer, and <i>vice versa</i>. However, it is uncertain whether the link is causal or just due to confounding factors. Using bidirectional Mendelian randomization analysis, we assessed the bidirectional causal relationship from a genetic level. <b>Methods:</b> Large genome-wide association studies yielded summary-level data for Type 2 diabetes and breast cancer. <b>Results:</b> Genetically predicted Type 2 diabetes presented no statistically significant association with overall breast cancer or its subtypes. Similarly, genetically predicted overall breast cancer or its subtypes had no causal effect on Type 2 diabetes. Sensitivity analyses yielded similar results. <b>Conclusion:</b> Our bidirectional Mendelian randomization studies revealed no causal links between Type 2 diabetes and breast cancer. Type 2 diabetes had no causal effect on the development of overall breast cancer, estrogen receptor (ER)+ or ER- subtypes. Overall breast cancer, ER+ and ER- subtypes had no causal effect on the development of Type 2 diabetes. The previously observed substantial relationships between Type 2 diabetes and breast cancer in observational studies could be explained by failing to account for confounders completely.