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| Association between endometrial cancer and breast cancer: a bidirectional Mendelian randomization study |
| LIANG Wei, GONG Xin, ZHANG Xiaoxiao, LI Shumiao
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| Department of Gynecology, Dong Fang Hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China |
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Abstract Objective To examine the causal relationship between endometrial cancer and breast cancer using bidirectional two-sample Mendelian randomization (MR) approach. Methods Genetic association data of endometrial cancer were collected through a meta analysis, including 54 884 participants and 9 464 330 single nucleotide polymorphisms (SNPs), and genetic association data of breast cancer were collected through the Breast Cancer Society Consortium, with 228 951 participants and 10 680 257 SNPs. A forward MR analysis was performed using the inverse variance weighted (IVW) method with 8 endometrial cancer-associated SNPs as instrumental variables and breast cancer as the study outcome, and a reverse MR analysis was performed with 112 breast cancer-associated SNPs as instrumental variables and endometrial cancer as the study outcome. The heterogeneity was assessed using the Cochran's Q test, the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression, and the robustness of the results was verified with the leave-one-out. Results Forward MR analysis results showed that patients with genetically predicted endometrial cancer had an increased risk of breast cancer compared to those without endometrial cancer (OR=1.083, 95%CI: 1.037-1.132). Reverse MR analysis showed that patients with genetically predicted breast cancer had an increased risk of endometrial cancer compared to those without breast cancer (OR=1.070, 95%CI: 1.010-1.134). Cochran's Q test detected no heterogeneity (P>0.05), and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results. Conclusion There are bidirectional causal relationship between endometrial cancer and breast cancer.
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Received: 20 December 2023
Revised: 12 March 2024
Published: 15 April 2024
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