The Causal Effect of Reproductive Factors on Breast Cancer: A Two-Sample Mendelian Randomization Study

Several studies have shown that female reproductive factors are associated with breast cancer (BC), but the results differ. We conducted two-sample MR in the present work. The raw data applied in the MR study were all from the Genome-wide association study (GWAS) database. The causal effect of reproductive factors on breast cancer were mainly estimated by the standard inverse variance weighted (IVW) method. Cochran's Q test and I² statistics were used to assess heterogeneity. The pleiotropy was evaluated by MR-Egger intercept test and MR-PRESSO. Finally, the leave-one-out analysis was performed to evaluate the robustness of the MR results. We found that there was a negative causal effect of the age at last live birth on BC (OR = 0.687, 95%CI = 0.539-0.875, p = 0.002) and positive effect of the age at menopause on BC (OR = 1.054, 95%CI = 1.034-1.075, p = 8.010 × 10^-8). Additionally, there were null effects of the age at menarche (OR = 0.977, 95%CI = 0.915-1.043, p = 0.484), the age at first sexual intercourse (OR = 1.053, 95%CI = 0.958-1.157, p = 0.284) and the age at first birth (OR = 0.981, 95%CI = 0.936-1.027, p = 0.404) on BC. All these results were reliable and stable. In conclusion, the present study showed that younger age at last birth and older age at menopause could increase the risk of BC.