Genetically predicted gynecologic surgery and risk of breast cancer in European population

Purpose: We conducted Mendelian randomization (MR) analyses to investigate the associations between gynecologic surgery and risk of breast cancer. Methods We performed MR using publicly accessible genome-wide association study (GWAS) datasets. Our primary analytical method was the inverse variance weighted (IVW) method. Additionally, we utilized complementary methods, including MR-Egger regression, weighted median, and MR-PRESSO. To assess potential horizontal pleiotropy, we conducted the MR-Egger intercept test and employed the global test for pleiotropic residuals and outliers through the MR-Presso method. We also assessed instrumental heterogeneity using the Cochran Q statistic. In addition, we conducted analyses of risk factors to further explore possible mediator relationships for causal inference. Results The initial findings from the IVW analysis reveal a statistically significant relationship between hysterectomy and ER- breast cancer (OR(Odds Ratio) = 82.73, 95% Confidence Interval (CI) = 1.45–4.73 × 10 3 , p = 0.032). These results were consistent with those obtained from MR-Egger regression, where bilateral ovariectomy demonstrates a statistically significant link with ER + breast cancer (OR = 6.42 × 10 − 2 , 95% CI = 6.08 × 10 − 3 − 0.68, p = 0.022). Importantly, the robustness of these findings was confirmed in all sensitivity analyses. Conclusion Our study reveals an association between gynecological surgery and breast cancer and menorrhagia and irregular menstruation is a potential mediator.