良性前列腺增生和男性群体膀胱癌的因果效应:双样本孟德尔随机化研究

Causal effects of benign prostatic hyperplasia and bladder cancer in male population:a two-sample Mendelian randomization study

目的利用两样本孟德尔随机化(MR)法探究良性前列腺增生(BPH)与男性群体膀胱癌(BCa)患病风险的因果效应。方法分别获取来自FinnGen R9数据库的BPH暴露数据(n=172961)以及UK Biobank的BCa结果数据(n=167020)的全基因组关联研究数据,经筛选使用其中显著的单核苷酸多态性位点作为工具变量,利用MR-PRESSO检验、MR Egger法和逆方差加权(IVW)法行异质性检验,去除离群值。使用MR Egger法、加权中值估计法、IVW法行MR分析,判断两者的因果联系。使用MR Egger回归检验、留一法检测结果的敏感性与多效性,确保分析结果可靠。结果在MR分析中,MR Egger法[OR=0.9999,95%CI=(0.9955,1.0036),P=0.832]、加权中值估计法[OR=0.9999,95%CI=(0.9983,1.0015),P=0.941]、IVW法[OR=1.0001,95%CI=(0.9990,1.0012),P=0.898]均未发现男性人群中BPH与BCa的风险之间存在因果关系。未发现显著的异质性或多效性,敏感性分析也没有发现与该假设相悖的结果。结论孟德尔随机化研究不支持良性前列腺增生与男性群体膀胱癌患病存在因果效应。

Objective To explore the causal effect of benign prostatic hyperplasia(BPH)on the risk of bladder cancer(BCa)in the male population using the two-sample Mendelian randomization(MR).Methods Genome-wide association study data for BPH exposure data(n=172961)from the FinnGen R9 database and BCa outcome data(n=167020)from the UK Biobank were obtained.Significant single nucleotide polymorphism loci were selected as instrumental variables after screening.Heterogeneity tests were conducted using the MR-PRESSO test,MR Egger method,and the inverse variance-weighted(IVW)method to remove outliers.MR analyses were performed using the MR Egger method,weighted median estimate,and IVW method to assess the causal relationship.The sensitivity and pleiotropy of the results were tested using MR Egger regression test and leave-one-out method to ensure reliability of the analysis.Results In this MR analysis,no causal relationship was found between BPH and the risk of BCa in the male population using the MR Egger method,weighted median estimate,and IVW me-thod.No significant heterogeneity or pleiotropy was detected,and sensitivity analysis did not reveal any results contrary to the hypothesis.Conclusion Mendelian randomization study does not support a causal effect of benign prostatic hyperplasia on the incidence of bladder cancer in the male population.