Association between breast and endometrial cancer: a two-way Mendelian randomization study

Abstract

Background Breast cancer is the most prevalent cancer worldwide, and endometrial cancer is one of the most common gynecological cancers. Observational studies have shown an association between breast and endometrial cancers, but it may be influenced by potential confounding factors. Meanwhile, Mendelian randomization (MR) studies can overcome these confounding factors to assess causality. Methods We obtained breast cancer data (122,977 breast cancer cases and 105,974 controls) and endometrial cancer data (12,906 endometrial cancer cases and 108,979 controls) indirectly from the Breast Cancer Association Coalition (BCAC) and the Endometrial Cancer Association Consortium (ECAC) through the IEU Open GWAS program(https://gwas.mrcieu.ac.uk/). Then, Inverse variance weighting (IVW) was used as the primary analysis method. Sensitivity analyses were performed by multiple MR methods to ensure the accuracy of the results. Results Based on the IVW approach, our study found that patients with endometrial cancer have an increased risk of developing breast cancer (OR:1.072; 95% CI: 1.027–1.119; p = 0.002), especially the ER + subtype of breast cancer (OR:1.072; 95% CI: 1.029–1.129; p = 0.001). Similarly, reverse MR analyses showed an increased risk of endometrial cancer in breast cancer patients (OR:1.078; 95% CI: 1.018–1.141; p = 0.009), particularly in those who were ER+ (OR:1.075; 95% CI: 1.015–1.137; p = 0.013). However, the bidirectional MR analyses did not reveal any proof of a connection between endometrial cancer and ER- breast cancer. Conclusions We found a bidirectional causal effect between breast and endometrial cancer, especially ER + breast cancer. Therefore, our study supports timely screening and prevention of endometrial cancer in breast cancer patients and vice versa. At the same time, we suggest further exploration of the potential pathogenic mechanisms between breast cancer and endometrial cancer.