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

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.

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).

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.

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.