Chen Junhao, Zhao Junxian, Zuo Jieming, Fu YuanZhi, Dong Haonan, Shi Hongjin, Zhang Yawei, Wang Haifeng, Fu Shi
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Urology, 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Kunming, Yunnan Province, China.
Medicine (Baltimore). 2025 May 2;104(18):e42369. doi: 10.1097/MD.0000000000042369.
This study explores the causal relationship between sedentary behavior and urological cancers, focusing on bladder cancer (BC), prostate cancer, and kidney cancer, using Bayesian Mendelian randomization and mediation analysis. A two-sample Mendelian randomization (MR) framework was employed, using genetic variants as instrumental variables. Bayesian and multivariate MR assessed causal effects of sedentary behaviors (TV watching, computer use, driving) on urological cancers. Sensitivity analyses (MR-Egger, MR-PRESSO, and Cochran Q) ensured robustness. Mediation analysis identified high-density lipoprotein (HDL) cholesterol ester levels as a primary mediator, validated through meta-analysis. Prolonged TV watching was significantly associated with increased BC risk (OR = 2.908; 95% CI = 1.221-6.930; P = .015). Mediation analysis showed small HDL cholesterol ester levels mediated 17.5% of this effect. No causal relationships were observed between computer use or driving and the cancers. Sensitivity analyses confirmed robust findings without heterogeneity or pleiotropy. Prolonged TV watching increases BC risk, mediated by small HDL cholesterol ester levels. Sedentary behavior is a modifiable risk factor, highlighting the importance of lifestyle interventions in prevention.
本研究采用贝叶斯孟德尔随机化和中介分析方法，探讨久坐行为与泌尿系统癌症（重点是膀胱癌、前列腺癌和肾癌）之间的因果关系。采用两样本孟德尔随机化（MR）框架，将基因变异用作工具变量。贝叶斯和多变量MR评估了久坐行为（看电视、使用电脑、开车）对泌尿系统癌症的因果效应。敏感性分析（MR-Egger、MR-PRESSO和 Cochr an Q）确保了结果的稳健性。中介分析确定高密度脂蛋白（HDL）胆固醇酯水平为主要中介因素，并通过荟萃分析进行了验证。长时间看电视与膀胱癌风险增加显著相关（比值比=2.908；95%置信区间=1.221-6.930；P=0.015）。中介分析表明，小HDL胆固醇酯水平介导了这种效应的17.5%。未观察到使用电脑或开车与这些癌症之间存在因果关系。敏感性分析证实了结果的稳健性，不存在异质性或多效性。长时间看电视会增加膀胱癌风险，由小HDL胆固醇酯水平介导。久坐行为是一个可改变的风险因素，突出了生活方式干预在预防中的重要性。
