CTLA4 genetic variants associated with urothelial bladder cancer susceptibility

Urol Oncol. 2024 Nov;42(11):374.e1-374.e10. doi: 10.1016/j.urolonc.2024.05.017. Epub 2024 Jun 15.

Abstract

Purpose: The study evaluated the relationship between the CTLA4 rs231775 (+49A>G) and rs231779 (+1822C>T) variants and susceptibility, stage, prognosis and response to treatment of the urothelial bladder cancer (UBC).

Methods: A total of 140 patients with UBC and 145 controls were enrolled. The patients were stratified as non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MICB), metastasis, recurrence, low/moderate/high/very high risk. Demographic, anthropometric, epidemiological, and clinical data were obtained from all individuals using a structured questionnaire. The CTLA4 variants were determined using real-time polymerase chain reaction (qPCR) and the genotypes were tested in the allelic, codominant, dominant, recessive, and overdominant genetic models.

Results: The UBC patients were older and mostly smokers (P < 0.001), with greater waist circumference, systolic, and diastolic arterial pressure (P = 0.005, P = 0.006, and P < 0.001, respectively) than controls. A protective effect for the UBC was observed among the patients carrying the heterozygote genotypes of the CTLA4 rs231775 [odds ratio (OR = 0.40; 95% confidence interval (CI): 0.160.98, P = 0.045) and rs231779 (OR = 0.35; 95% CI: 0.14-0.87, P = 0.024). R2 Nagelkerke analysis demonstrated that a model with age and smoking added to the CTLA4 rs231775 SNVs explained 77.0% of the susceptibility to UBC and a model with age and smoking added to the CLTA4 rs231779 explained 77.2% of the susceptibility to UBC.

Conclusion: The CTLA4 rs231775 AG and rs231779 CT heterozygous genotypes in the overdominant model together with age and smoking may be useful as potential biomarkers for the UBC susceptibility.

Keywords: Bladder cancer; CTLA4; Overdominant; Single nucleotide variant; Urothelial bladder cancer.

MeSH terms

  • Aged
  • CTLA-4 Antigen* / genetics
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / pathology

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human