Gout Does Not Causally Increase the Risk of Endometrial Cancer: Evidence from Mendelian Randomization

Abstract

Background: Gout is a prevalent condition associated with chronic inflammation and metabolic dysregulation, both of which are known risk factors for various malignancies. However, the potential causal relationship between gout and endometrial cancer has not been systematically explored. Methods: A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) summary statistics to evaluate the potential causal effect of genetically predicted gout on the risk of endometrial cancer. Genetic variants strongly associated with gout were selected as instrumental variables. The inverse variance weighted (IVW) method was used for the primary analysis, supplemented by MR-Egger and weighted median approaches. Sensitivity analyses included tests for pleiotropy, heterogeneity, and leave-one-out stability. Results: The MR analysis revealed no significant causal effect of gout on the risk of developing endometrial cancer (IVW OR = 1.015, 95% CI: 0.957–1.077, P = 0.614). Sensitivity analyses indicated no evidence of pleiotropy or heterogeneity, and the leave-one-out analysis confirmed the robustness of the results. Conclusion: This MR analysis found no evidence supporting a causal effect of gout on the risk of endometrial cancer. These results suggest that genetic predisposition to gout does not significantly influence the likelihood of developing endometrial cancer. Further studies in diverse populations are needed to confirm these findings and explore potential shared mechanisms linking metabolic disorders to cancer development.