Abstract
Background: Observational studies have suggested a possible association between benign prostate hyperplasia (BPH) and bladder cancer (BLCA). However, these studies are prone to errors and limitations or confounding factors, making them unsuitable for assessing the causal relationship between BPH and BLCA. Objective: Two-sample Mendelian randomization (MR) was performed to determine a possible association between genetically predicted BPH and the risk of BLCA. Methods: A two-sample MR analysis was performed utilizing the Integrative Epidemiology Unit genome-wide association (GWAS) database of the Medical Research Council, United Kingdom A series of control steps, including five primary methods, were performed to identify the most suitable instrumental variables (IVs) for MR analysis. Sensitivity analysis was conducted to avoid statistical errors, including heterogeneity and pleiotropic bias. Results: Genetic variants associated with BPH (P < 5 × 10-8) and BLCA (P < 5 × 10-6) were identified as instrumental variables and assessed using GWAS summary data (BPH, 4,670 cases vs. 458,340 controls; BLCA, 1,279 cases vs. 372,016 controls). BPH exhibited a positive effect on the occurrence of BLCA (inverse variance weighted (IVW), odds ratio (OR) = 1.095, 95% confidence interval (CI) = 1.030-1.165, p = 0.003), but there was no causal effect for BLCA on BPH (IVW, OR = 1.092, 95% CI = 0.814-1.465, p = 0.554). Conclusion: Genetically predicted BPH was associated with a higher risk of BLCA in all histological subtypes. In contrast, the evidence was not significant to back the causality of genetically induced BLCA on BPH. These findings indicate that BPH plays a key role in developing BLCA in the European population. Further studies are needed to uncover the underlying mechanisms.