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非甾体抗炎药使用与良性前列腺增生风险之间的因果关联:一项单变量和多变量孟德尔随机化研究

Causal association between non-steroidal anti-inflammatory drugs use and the risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study.

作者信息

Peng Zi-He, Li Ming-Rui, He Min-Xin, Liu Jing, Dou Jia-Hao, Wang Ya-Wen, Dong Yao, Yan Chong, Li Zi-Hao, Chong Tie, Li Zhao-Lun

机构信息

Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.

Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

出版信息

BMC Med Genomics. 2025 Mar 31;18(1):60. doi: 10.1186/s12920-025-02128-1.

Abstract

BACKGROUND

The results of earlier observational research on the relationships between the usage of non-steroidal anti-inflammatory medicines (NSAIDs) and the risk of benign prostatic hyperplasia (BPH) have been inconsistent.

METHODS

To assess these associations, we performed both univariable and multivariable Mendelian randomization (MR) studies. Instrumental variables (IVs) associated with exposures at the significance level (p < 5 × 10) were selected from a comprehensive meta-analysis conducted by the United Kingdom Biobank (UKB). Summary data for BPH were obtained from the FinnGen consortium, which comprised 30,066 cases and 119,297 controls. Sensitivity analyses were performed to evaluate heterogeneity and pleiotropy.

RESULTS

We found evidence by univariable MR (UVMR) that genetically predicted NSAIDs use increased the risk of BPH (odds ratio [OR] per unit increase in log odds NSAIDs use: 1.164, 95% confidence interval [CI]: 1.041-1.302, p = 0.008). After controlling for inflammation in multivariable MR (MVMR), the link persisted (OR: 1.165, 95% CI: 1.049-1.293, p = 0.004). There were no indications of potential heterogeneity and pleiotropy in UVMR and MVMR analyses.

CONCLUSION

The results of the MR estimates suggest that genetically predicted NSAIDs use may elevate the risk of BPH. This outcome prompts the imperative for deeper exploration into potential underlying mechanisms.

摘要

背景

早期关于非甾体类抗炎药(NSAIDs)使用与良性前列腺增生(BPH)风险之间关系的观察性研究结果并不一致。

方法

为评估这些关联,我们进行了单变量和多变量孟德尔随机化(MR)研究。与暴露相关的工具变量(IVs)在显著性水平(p < 5×10)下从英国生物银行(UKB)进行的一项综合荟萃分析中选取。BPH的汇总数据来自芬兰基因联盟,该联盟包括30,066例病例和119,297例对照。进行敏感性分析以评估异质性和多效性。

结果

我们通过单变量MR(UVMR)发现证据表明,基因预测的NSAIDs使用增加了BPH的风险(NSAIDs使用对数优势每单位增加的优势比[OR]:1.164,95%置信区间[CI]:1.041 - 1.302,p = 0.008)。在多变量MR(MVMR)中控制炎症后,这种关联仍然存在(OR:1.165,95% CI:1.049 - 1.293,p = 0.004)。UVMR和MVMR分析中没有潜在异质性和多效性的迹象。

结论

MR估计结果表明,基因预测的NSAIDs使用可能会增加BPH的风险。这一结果促使有必要深入探索潜在的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ebb/11956187/0dde58df7bb5/12920_2025_2128_Fig1_HTML.jpg

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