Association of immune checkpoint-related polymorphisms in PD-1, PD-L1, and CTLA-4 genes with susceptibility to genitourinary cancer: a meta-analysis

This meta-analysis explored the association of immune checkpoint-related single-nucleotide polymorphisms (SNPs) in programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) genes with susceptibility to various genitourinary (GU) cancers, including urothelial carcinoma (UC), renal cell carcinoma (RCC), and prostate cancer (PCa). PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies from inception to April 2026. Six SNPs, including PD-1 (rs2227981), PD-L1 (rs4143815), and CTLA-4 (rs3087243, rs231775, rs5742909, and rs11571302), were examined. The relationships between the SNPs and cancer susceptibility were evaluated using pooled odds ratios (ORs) and 95% confidence intervals (CIs) for dominant, recessive, and allele models. This study considered 16 case-control studies. PD-L1 rs4143815 was associated with a significantly decreased risk of UC in Asian populations under the dominant model (CC + CG vs. GG: OR = 0.34, 95% CI = 0.14-0.87). CTLA-4 rs5742909 polymorphism was associated with an increased risk of GU cancer in dominant model (TT + TC vs. CC: OR = 1.41, 95% CI = 1.11-1.80) and allele model (T vs. C: OR = 1.34, 95% CI = 1.05-1.72). A significantly increased risk of UC was further identified among Asian population in the dominant model (OR = 1.56, 95% CI = 1.04-2.34). No significant associations were observed for the other SNPs. In conclusion, specific polymorphisms in immune checkpoint-related genes, particularly PD-L1 rs4143815 and CTLA-4 rs5742909, are associated with susceptibility to GU cancer in Asian populations.