基于孟德尔随机化和人群横断面研究探索糖尿病与泌尿系统肿瘤的相关性

Association of diabetes mellitus with urinary tract tumors: evidence from Mendelian randomization and population-based cross-sectional study

摘要

目的：探讨糖尿病（diabetes mellitus，DM）对泌尿系统肿瘤发生风险的影响。方法：利用IEU OpenGWAS和FinnGen等数据库的汇总统计数据进行两样本孟德尔随机化（Mendelian randomization，MR）分析；通过横断面人群分析进行表型验证，并采用二次MR分析以增强证据强度。结果：初步MR分析显示，2型糖尿病（type 2 diabetes mellitus，T2DM）与膀胱癌存在弱关联（OR=1.001，95% CI：1.000～1.001， P=0.010）；DM（OR=1.016，95% CI：1.001～1.032， P=0.037）和T2DM（OR=1.002，95% CI：1.001～1.002， P=0.021）均被证实为前列腺癌的危险因素，该结果得到二次MR分析的支持，并经横断面分析验证。亚组分析显示，T2DM增加前列腺原位癌风险（OR=2.114，95% CI：1.062～4.240， P=0.032）。结论：T2DM增加前列腺癌风险，尤其对原位癌的影响更为显著。

Abstract

Objective: To investigate the impact of diabetes mellitus (DM) on the risk of developing urinary tract tumors. Methods: Two-sample Mendelian randomization (MR) analyses were conducted using summary statistics from the IEU OpenGWAS and FinnGen databases. Phenotypic validation was conducted using cross-sectional population analysis, and secondary MR analysis was performed to enhance the strength of evidence. Results: Preliminary MR analysis revealed a weak association between type 2 diabetes mellitus (T2DM) and bladder cancer (OR=1.001, 95% CI: 1.000-1.001, P=0.010). DM (OR=1.016, 95% CI: 1.001-1.032, P=0.037) and T2DM (OR=1.002, 95% CI: 1.001-1.002, P=0.021) were confirmed as risk factors for prostate cancer (PCa), with the findings supported by secondary MR, and were validated by cross-sectional analysis. Subgroup analysis showed that T2DM increased the risk of PCa in situ (OR=2.114, 95% CI: 1.062-4.240, P=0.032). Conclusion: T2DM increases the risk of PCa, especially for carcinoma in situ.

关键词

孟德尔随机化 / 糖尿病 / 泌尿系统 / 肿瘤 / 前列腺癌 / 膀胱癌 / 肾癌 / 横断面研究

Key words

Mendelian randomization / diabetes mellitus / urinary system / tumor / prostate cancer / bladder cancer / kidney cancer / cross-sectional study

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基金资助

广西自然科学基金资助项目(2022JJB140197)

国家自然科学基金资助项目(82460596)