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

Abstract

Abstract 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 × 103, 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.