Causal Associations Between the Presence of Prostate Cancer or Testosterone Levels and Bladder Cancer Risk: A Mendelian Randomization Study.

[BACKGROUND] Previous observational studies and meta-analyses have indicated that prostate cancer and testosterone levels could be potential risk factors for bladder cancer. However, these studies are vulnerable to confounding variables and reverse causality. Thus, we conducted a 2-sample Mendelian Randomization (MR) study to elucidate the causal link between the presence of prostate cancer or testosterone levels and bladder cancer.

[METHODS] We acquired summary statistics for the presence of prostate cancer or testosterone levels and bladder cancer from genome-wide association studies (GWAS). MR analysis was employed to investigate the potential causal relationship between the presence of prostate cancer or testosterone levels and bladder cancer. The primary method employed was the inverse variance weighted (IVW) method, with results rigorously assessed through sensitivity analysis.

[RESULTS] IVW Mendelian randomization results demonstrated that prostate cancer was causally associated with an elevated risk of bladder cancer in FinnGen (OR 1.22, 95% CI, 1.13-1.31, P < .001), UK Biobank (OR 17.9, 95% CI, 3.28-97.62, P < .001), and the PRACTICAL database (OR 1.13, 95% CI, 1.05-1.22, P < .001). There was no evidence of heterogeneity in the effects of genetic factors on bladder cancer risk, as indicated by Cochran's Q statistical test (FinnGen Q = 68.86, P = .13; UK Biobank Q = 29.05, P = .61; PRACTICAL Q = 108.88, P = .48). Sensitivity analyses confirmed the stability and robustness of the genetically determined risk effect of prostate cancer on bladder cancer. However, there was no causal link between testosterone levels and bladder cancer (P > .05).

[CONCLUSIONS] This study identified that genetically predicted prostate cancer was causally linked to an increased risk of bladder cancer. Appropriate measures should be taken to prevent the subsequent development of bladder cancer in patients with prostate cancer.