[Association of CTLA-4 gene polymorphisms with the genetic susceptibility and prognosis of patients with Bladder urothelial carcinoma].

Objective: To assess the association of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms with the prognosis of patients with Bladder urothelial carcinoma (BUC).

Methods: From February 2019 to October 2020, 256 BUS patients treated at the Xinxiang Central Hospital were selected as the study group, whilst 250 healthy individuals were selected as the control group. Genotypes of rs5742909 (-318C/T), rs231775 (+49A/G) and rs4553808 (-1661A/G) were determined by PCR-restriction fragment length polymorphism assay. The frequencies of genotypes and alleles of the CTLA-4 gene were compared between the two groups. All patients had undergone surgical treatment and were followed up for 3 years and divided into good prognosis group (n = 166) and poor prognosis group (n = 86) based on the status of disease. The distribution of alleles and genotypes were compared, and Kaplan-Meier analysis was used to assess the association of genetic polymorphisms with the prognosis.

Results: No significant difference was found in the gender, age, BMI, smoking history and alcohol use between the two groups (P > 0.05). The frequencies of GG genotype and G allele for the rs231775 (+49A/G) and rs4553808 (-1661A/G) loci were significantly higher in the study group compared with the control group (P < 0.05), whilst no statistical difference was found in the genotypic and allelic frequency for the rs5742909 locus between the two groups (P > 0.05). Among the 252 subjects who had completed follow-up, 86 had poor prognosis and 166 had good prognosis. The frequencies of GG genotype and G allele at the rs231775 (+49A/G) and rs4553808 (-1661A/G) loci were significantly lower in the good prognosis group compared with the poor prognosis group (P < 0.05). Kaplan-Meier survival curve analysis showed that the survival time of patients with GG genotype for the rs231775 (+49A/G) and rs4553808 (-1661A/G) loci was significantly shorter than patients with AA or AG genotypes (Log Rank 2 = 13.654, 9.974, P < 0.001).

Conclusion: The polymorphisms of the rs231775 and rs4553808 loci of the CTLA-4 gene are associated with genetic susceptibility and poor prognosis for BUC, and a higher GG genotypic frequency may increase the risk for infection and poor prognosis of the patients.