AKT1 polymorphisms and survival of early stage non-small cell lung cancer

J Surg Oncol. 2012 Feb;105(2):167-74. doi: 10.1002/jso.22071. Epub 2011 Aug 12.

Abstract

Background and objectives: This study was conducted to investigate the impact of polymorphisms in the AKT1 gene on the survival of early stage non-small cell lung cancer (NSCLC) patients.

Methods: Three hundred and ten patients with surgically resected NSCLC were enrolled. The rs3803300, rs1130214, rs3730358, rs1130233, and rs2494732 single nucleotide polymorphisms (SNPs) in the AKT1 gene were investigated. The genotype and haplotype associations with overall survival (OS) and disease free survival (DFS) were analyzed.

Results: The three SNPs (rs3803300, rs1130214, and rs2494732) were significantly associated with survival outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS were decreased in a dose-dependent manner as the number of bad genotypes increased (P(trend) = <1.0 × 10(-4) and 0.001, respectively). Patients with 2 bad genotypes had a significantly worse OS and DFS compared with those with 0 bad genotypes (adjusted hazard ratio (HR) = 3.08, 95% confidence interval (CI) = 1.61-5.89, P = 0.001; and adjusted HR = 2.04, 95% CI = 1.22-3.43, P = 0.01).

Conclusions: These results suggest that the AKT1 polymorphisms could be used as prognostic markers for the patients with early-stage NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Follow-Up Studies
  • Genotype
  • Haplotypes / genetics*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics*
  • Survival Rate

Substances

  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt