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

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.