Association between non-neoplastic bladder diseases and bladder cancer risk: insights from Mendelian randomization studies

Abstract Purpose Our aim is to explore the relation between non-neoplastic bladder diseases and bladder cancer (BC) from a genetic level utilizing Mendelian randomization (MR). Methods 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. Results 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. Conclusion 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.