CTLA-4 +49A>G polymorphism is associated with advanced non-small cell lung cancer prognosis

Respiration. 2011;82(5):439-44. doi: 10.1159/000329345. Epub 2011 Aug 11.

Abstract

Background: Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by downregulating T cell activation. The most studied +49A>G polymorphism of the CTLA-4 gene has been associated with several autoimmune diseases. However, little is known about the association between this functional polymorphism of CTLA-4 and cancer prognosis.

Objective: To investigate the association between CTLA-4 +49A>G polymorphism and prognosis of advanced non-small cell lung cancer (NSCLC) patients in a Chinese population.

Methods: The CTLA-4 +49A>G polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 338 advanced NSCLC patients.

Results: The frequencies of CTLA-4 +49 GG, GA and AA in advanced NSCLC patients were 44.4%, 42.0% and 13.6%, respectively. No significant association was observed between CTLA-4 +49A>G polymorphism and clinicopathologic features of advanced NSCLC including gender, histopathological type, clinical stage and tumor markers. Patients with the AA genotype had a survival time of 9.8 months, significantly shorter than those with the GG genotype (12.5 months) or the GA genotype (12.0 months) (p < 0.001; log-rank test). Multivariate Cox analysis further revealed that the CTLA-4 +49AA genotype is an independent adverse prognostic indicator for NSCLC patients.

Conclusion: Our data suggest that the polymorphism of CTLA-4 +49A>G is a prognostic predictor for advanced NSCLC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics*
  • Biomarkers, Tumor / genetics*
  • CTLA-4 Antigen / genetics*
  • CTLA-4 Antigen / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • China
  • Down-Regulation
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lymphocyte Activation / genetics
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Proportional Hazards Models

Substances

  • Biomarkers, Tumor
  • CTLA-4 Antigen
  • CTLA4 protein, human