Ren Wenbiao, Zhu Yewen
Department of Urology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
Department of Urology and Pediatric Urology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
Clin Genitourin Cancer. 2025 Jun;23(3):102334. doi: 10.1016/j.clgc.2025.102334. Epub 2025 Mar 19.
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.
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.
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).
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.
既往的观察性研究和荟萃分析表明，前列腺癌和睾酮水平可能是膀胱癌的潜在危险因素。然而，这些研究容易受到混杂变量和反向因果关系的影响。因此，我们进行了一项两样本孟德尔随机化（MR）研究，以阐明前列腺癌的存在或睾酮水平与膀胱癌之间的因果关系。
我们从全基因组关联研究（GWAS）中获取了前列腺癌或睾酮水平以及膀胱癌的汇总统计数据。采用MR分析来研究前列腺癌的存在或睾酮水平与膀胱癌之间的潜在因果关系。采用的主要方法是逆方差加权（IVW）法，并通过敏感性分析对结果进行严格评估。
IVW孟德尔随机化结果表明，在芬兰基因库（比值比1.22，95%置信区间，1.13 - 1.31，P <.001）、英国生物银行（比值比17.9，95%置信区间，3.28 - 97.62，P <.001）和PRACTICAL数据库（比值比1.13，95%置信区间，1.05 - 1.22，P <.001）中，前列腺癌与膀胱癌风险升高存在因果关联。Cochran's Q统计检验表明，遗传因素对膀胱癌风险的影响不存在异质性（芬兰基因库Q = 68.86，P =.13；英国生物银行Q = 29.05，P =.61；PRACTICAL Q = 108.88，P =.48）。敏感性分析证实了前列腺癌对膀胱癌的遗传决定风险效应的稳定性和稳健性。然而，睾酮水平与膀胱癌之间不存在因果关系（P >.05）。
本研究确定，基因预测的前列腺癌与膀胱癌风险增加存在因果联系。对于前列腺癌患者，应采取适当措施预防随后发生膀胱癌。
