The Causal Effect of Reproductive Factors on Breast Cancer: A Two-Sample Mendelian Randomization Study
Lijun Jia, Wei Lv, Liang Liang, Yuguang Ma, Xingcong Ma, Shuqun Zhang, Yonglin Zhao
Abstract
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.