Abstract
BACKGROUND: Cyclin-dependent kinase 8 (CDK8) has been implicated in various tumors, with its role differing across tumor types. However, the association between CDK8 polymorphisms and bladder cancer (BC) remains unclear. This study investigated the association between CDK8 polymorphisms and BC susceptibility and prognosis. METHODS: This case-control study included 271 patients with BC and 381 healthy controls. Two-tag single-nucleotide polymorphisms in the CDK8 gene (rs17083838 and rs7992670) were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed using SNPstats and SPSS software to assess genetic associations. RESULTS: The AG/AA genotypes of rs17083838 were associated with a significantly reduced risk of BC under the dominant model (P < 0.001, odds ratio [95% confidence interval] = 0.50 [0.33-0.76]). Stratified analysis revealed that the AG genotype of rs17083838 increased the risk of postoperative recurrence in patients with stage IV BC (P = 0.007). For rs7992670, females with the AG/AA genotype exhibited a 2.07-fold higher risk of BC than males, whereas smokers with the same genotype showed a 2.13-fold higher risk than non-smokers. The GG genotype of rs7992670 was associated with better overall survival in patients with stage III BC (P = 0.023). Among patients with recurrent muscle-invasive BC, those with the GG/AA genotype showed significantly improved survival compared with those carrying the AG genotype (P = 0.023). CONCLUSIONS: CDK8 polymorphisms influence BC susceptibility and prognosis, with rs17083838 showing a protective effect and rs7992670 being associated with increased risk and survival outcomes in specific subgroups. IMPACT: This study highlights the potential of CDK8 polymorphisms as biomarkers for BC susceptibility and prognosis, emphasizing the need for further research.