Causal relationship between benign prostatic hyperplasia and prostate cancer: a bidirectional Mendelian randomization analysis.

IF 3.6 4区医学 Q1 MEDICINE, GENERAL & INTERNAL Postgraduate Medical Journal Pub Date : 2024-11-15 DOI:10.1093/postmj/qgae163

Yi Zhang, Guangyang Ou, Rongkang Li, Lei Peng, Jianguo Shi

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Abstract

Objective: Our aim is to explore the relation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) from a genetic level utilizing Mendelian randomization (MR).

Methods: The IEU genome-wide association studies database was surveyed for single nucleotide polymorphisms (SNPs) associated with BPH, PCa, and PCa (validation cohort). Single nucleotide polymorphisms were subjected to stringent quality control based on rigorous screening criteria. BPH and PCa risk were evaluated using the inverse-variance weighted method (IVW), MR-Egger, simple mode, weighted median, and weighted mode. Horizontal pleiotropy of single nucleotide polymorphisms was assessed using the MR-Egger intercept test, while heterogeneity was evaluated using Cochran's Q test. Reverse causality was assessed by evaluating PCa as the exposure and BPH as the outcome. A validation database was used to verify the exposure and outcome.

Results: The risk of PCa increased significantly with genetically predicted BPH (IVW: OR [95% CI] = 1.3849 × 107 [2330, 8.2294 × 1010], P = 2.0814 × 10-4). In reverse MR analysis, PCa also increased the risk of BPH (IVW: OR [95% CI] = 1.0011 [1.0003, 1.0019], P = 0.0031). The findings were consistent with the MR analysis results of the PCa validation cohort. Sensitivity analyses indicated the presence of heterogeneity but no horizontal pleiotropy.

Conclusion: The study presents proof of a significant bidirectional causal relationship between genetically predicted BPH and an increased risk of PCa. Key message Three research questions and three bullet points What is already known on this topic? Observational studies suggest a controversial relationship between BPH and PCa. MR allows investigation of causality using genetic variants as instrumental variables (IVs). What does this study add? The study presents proof of a significant bidirectional causal relationship between genetically predicted BPH and an increased risk of PCa. How this study might affect research, practice, or policy? Recognizing the bidirectional relationship between BPH and PCa, men diagnosed with BPH may benefit from more stringent PCa screening protocols.

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良性前列腺增生与前列腺癌之间的因果关系：双向孟德尔随机分析。

目的我们的目的是利用孟德尔随机化方法（MR）从遗传学层面探讨良性前列腺增生症（BPH）与前列腺癌（PCa）之间的关系：方法：在 IEU 全基因组关联研究数据库中调查了与良性前列腺增生症（BPH）、前列腺癌（PCa）和前列腺癌（验证队列）相关的单核苷酸多态性（SNPs）。根据严格的筛选标准，对单核苷酸多态性进行了严格的质量控制。采用逆方差加权法（IVW）、MR-Egger、简单模式、加权中位数和加权模式对良性前列腺增生症和 PCa 风险进行了评估。单核苷酸多态性的水平多向性采用 MR-Egger 截距检验进行评估，异质性采用 Cochran's Q 检验进行评估。评估反向因果关系时，将 PCa 作为暴露因素，而将良性前列腺增生作为结果。验证数据库用于验证暴露和结果：结果：PCa 的风险随着基因预测的良性前列腺增生而显著增加（IVW：OR [95% CI] = 1.3849 × 107 [2330, 8.2294 × 1010]，P = 2.0814 × 10-4）。在反向 MR 分析中，PCa 也会增加罹患良性前列腺增生症的风险（IVW：OR [95% CI] = 1.0011 [1.0003, 1.0019]，P = 0.0031）。这些结果与 PCa 验证队列的 MR 分析结果一致。敏感性分析表明存在异质性，但没有横向褶皱：该研究证明了遗传预测的良性前列腺增生症与 PCa 风险增加之间存在显著的双向因果关系。关键信息三个研究问题和三个要点关于这一主题的已知信息有哪些？观察性研究表明良性前列腺增生症与 PCa 之间的关系存在争议。磁共振可将遗传变异作为工具变量（IV）来研究因果关系。本研究有何新意？本研究证明了遗传预测的良性前列腺增生与 PCa 风险增加之间存在显著的双向因果关系。本研究对研究、实践或政策有何影响？认识到良性前列腺增生症与 PCa 之间的双向关系，被诊断出患有良性前列腺增生症的男性可能会受益于更严格的 PCa 筛查方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Postgraduate Medical Journal 医学-医学：内科

CiteScore

8.50

自引率

2.00%

发文量

131

审稿时长

2.5 months

期刊介绍： Postgraduate Medical Journal is a peer reviewed journal published on behalf of the Fellowship of Postgraduate Medicine. The journal aims to support junior doctors and their teachers and contribute to the continuing professional development of all doctors by publishing papers on a wide range of topics relevant to the practicing clinician and teacher. Papers published in PMJ include those that focus on core competencies; that describe current practice and new developments in all branches of medicine; that describe relevance and impact of translational research on clinical practice; that provide background relevant to examinations; and papers on medical education and medical education research. PMJ supports CPD by providing the opportunity for doctors to publish many types of articles including original clinical research; reviews; quality improvement reports; editorials, and correspondence on clinical matters.

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