Distribution of PD-1.5 Gene Variant (rs2227981): A Possible Approach for Risk Assessment in Bladder Cancer

Background/Aim: Immune checkpoint pathways are central to tumor immune evasion, and genetic variants of programmed death-1 (PD-1) may influence cancer susceptibility. This study evaluates the association between the PD-1.5 (rs2227981) polymorphism and the risk of bladder cancer (BC) in the Turkish population. Materials and Methods: The study included 151 participants, consisting of 53 patients with BC and 98 healthy control individuals. Genotyping of the PD-1.5 (C/T) polymorphism was carried out using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype and allele distributions were compared between groups, and logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: The CC, CT, and TT genotypes were observed in 33.96%, 43.40%, and 22.64% of patients and in 48.98%, 40.82%, and 10.20% of controls, respectively. The recessive model (TT vs. CC + CT) differed significantly between cases and controls (p = 0.023), and the C allele was less frequent in patients (p = 0.039). In univariate logistic regression, carriage of the T allele showed a borderline association with increased BC risk (OR = 1.867, 95% CI = 0.934–3.732; p = 0.077), whereas carriage of the C allele was significantly associated with reduced risk (OR = 0.388, 95% CI = 0.155–0.972; p = 0.043). In multivariate models adjusted for age, sex, and smoking status, the C allele remained an independent protective factor (adjusted OR = 0.319, 95% CI = 0.112–0.906; p = 0.045), while older age, male sex, and smoking were independently associated with an elevated risk of BC. Conclusions: The PD-1.5 (rs2227981) polymorphism appears to influence bladder cancer susceptibility in the Turkish population, with the TT genotype conferring increased risk and the C allele providing protection. These findings highlight the potential role of PD-1.5 as a genetic marker for BC risk, although validation in larger and more diverse cohorts is required.<br /> <div> <br /> </div>