Zhang Yi, Li Rongkang, Zhang Shaohua, Li Hangxu
Department of Urology, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, No. 2 Heping Road, Section 5, Linghe District, Jinzhou, 121001, Liaoning, China.
Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, No. 2 Renmin Street, Section 5, Guta District, Jinzhou, 121002, Liaoning, China.
Postgrad Med J. 2025 Jan 23;101(1192):156-162. doi: 10.1093/postmj/qgae121.
Our aim is to explore the relation between non-neoplastic bladder diseases and bladder cancer (BC) from a genetic level utilizing Mendelian randomization (MR).
Single nucleotide polymorphisms (SNPs) related to cystitis, bladder stones, and neuropathic bladder were gathered from the IEU genome-wide association studies database. Quality control on SNPs was performed via stringent screening criteria. The relation between non-neoplastic bladder diseases and BC risk was evaluated using inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods. Cochran's Q test was conducted to assess the heterogeneity of SNPs; in addition, the MR-Egger intercept test was employed to examine the horizontal pleiotropy of SNPs. Exposure and outcomes were validated using a validation database. Finally, BC was used as the exposure and non-neoplastic bladder diseases as the outcome to evaluate reverse causality.
The outcomes showcased that genetically predicted cystitis is significantly correlated to a raised risk of BC (inverse-variance weighted: odds ratio [95%] = 1.1737 [1.0317, 1.3352], P = .0149), consistent with the BC validation cohort in the MR analysis. Nevertheless, no causal relation was found between bladder stone and neuropathic bladder with BC risk (P > .05). In this study, sensitivity analysis indicated no heterogeneity or horizontal pleiotropy.
The study presents proof of a genetic-level causal relation between cystitis and increased BC risk, while bladder stones and neuropathic bladder do not show similar associations.
我们的目标是利用孟德尔随机化（MR）从基因水平探索非肿瘤性膀胱疾病与膀胱癌（BC）之间的关系。
从IEU全基因组关联研究数据库收集与膀胱炎、膀胱结石和神经源性膀胱相关的单核苷酸多态性（SNP）。通过严格的筛选标准对SNP进行质量控制。使用逆方差加权、MR-Egger、加权中位数、简单模式和加权模式方法评估非肿瘤性膀胱疾病与BC风险之间的关系。进行Cochran's Q检验以评估SNP的异质性；此外，采用MR-Egger截距检验来检验SNP的水平多效性。使用验证数据库对暴露因素和结局进行验证。最后，以BC作为暴露因素，非肿瘤性膀胱疾病作为结局来评估反向因果关系。
结果表明，基因预测的膀胱炎与BC风险升高显著相关（逆方差加权：优势比[95%] = 1.1737 [1.0317, 1.3352]，P = 0.0149），这与MR分析中的BC验证队列一致。然而，未发现膀胱结石和神经源性膀胱与BC风险之间存在因果关系（P > 0.05）。在本研究中，敏感性分析表明不存在异质性或水平多效性。
该研究提供了膀胱炎与BC风险增加之间存在基因水平因果关系的证据，而膀胱结石和神经源性膀胱未显示出类似的关联。
