Huang Haijun, Hu Zhiquan, Chen Zhi, Zhang Yucong, Yang Chunguang
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Transl Androl Urol. 2025 Mar 30;14(3):661-668. doi: 10.21037/tau-2024-673. Epub 2025 Mar 26.
Benign prostate hyperplasia (BPH) and prostate cancer (PCa) share several similarities, including androgen dependency and parallel increases in prevalence with age. Although PCa lags by 15-20 years, no causal association has been identified between BPH and PCa. To investigate the potential causal links between BPH and PCa, this study was performed in a two-sample Mendelian randomization (MR) design.
We retrieved single-nucleotide polymorphisms (SNPs) associated with BPH from genome-wide association studies (GWAS), which were obtained from the Integrative Epidemiology Unit database, and conducted a two-sample MR analysis to explore the causal relationship between BPH and PCa. The exposure dataset included 13,118 BPH cases and 72,799 controls, while the outcome dataset comprised 9,132 PCa cases and 173,493 controls, all of European ancestry. Four SNPs were selected as instrumental variables (IVs) after stringent filtering for linkage disequilibrium and potential confounding factors. The causal effect was estimated using the inverse-variance-weighted (IVW) method, supplemented by sensitivity analyses to assess heterogeneity and pleiotropy.
The IVW analysis revealed that genetically predicted BPH was causally associated with a 1.02-fold increased risk of PCa [95% confidence interval (CI): 1.0076-1.0286, P<0.001]. Sensitivity analyses, including MR-Egger regression and leave-one-out analysis, confirmed the robustness of these findings, with no significant heterogeneity or pleiotropy detected.
This study provides genetic evidence supporting a causal relationship between BPH and an increased risk of PCa. These findings suggest that BPH may contribute to the development of PCa, potentially guiding future clinical practices in screening, diagnosis, and treatment strategies for BPH patients to mitigate PCa risk. Further validation in diverse populations and clinical studies is warranted to confirm these findings.
良性前列腺增生（BPH）和前列腺癌（PCa）有若干相似之处，包括雄激素依赖性以及患病率随年龄平行上升。尽管前列腺癌的发病滞后15 - 20年，但尚未确定BPH与PCa之间存在因果关联。为了研究BPH与PCa之间潜在的因果联系，本研究采用两样本孟德尔随机化（MR）设计进行。
我们从综合流行病学单位数据库获取的全基因组关联研究（GWAS）中检索与BPH相关的单核苷酸多态性（SNP），并进行两样本MR分析以探究BPH与PCa之间的因果关系。暴露数据集包括13118例BPH病例和72799例对照，而结局数据集包括9132例PCa病例和173493例对照，所有样本均为欧洲血统。在对连锁不平衡和潜在混杂因素进行严格筛选后，选择了四个SNP作为工具变量（IV）。使用逆方差加权（IVW）方法估计因果效应，并辅以敏感性分析以评估异质性和多效性。
IVW分析显示，基因预测的BPH与PCa风险增加1.02倍存在因果关联[95%置信区间（CI）：1.0076 - 1.0286，P < 0.001]。敏感性分析，包括MR - Egger回归和留一法分析，证实了这些发现的稳健性，未检测到显著的异质性或多效性。
本研究提供了遗传证据，支持BPH与PCa风险增加之间存在因果关系。这些发现表明BPH可能促成PCa的发生，这可能为未来针对BPH患者的筛查、诊断和治疗策略的临床实践提供指导，以降低PCa风险。需要在不同人群和临床研究中进行进一步验证以证实这些发现。
