Genetically predicted benign prostate hyperplasia causally affects prostate cancer: a two-sample Mendelian randomization.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.