ATM gene polymorphisms are associated with poor prognosis of non-small cell lung cancer receiving radiation therapy

Aging (Albany NY). 2020 Apr 24;12(8):7465-7479. doi: 10.18632/aging.103094. Epub 2020 Apr 24.

Abstract

We investigated the prognostic significance of ataxia telangiectasia mutated (ATM) single nucleotide polymorphisms (SNPs) in 720 Han Chinese non-small cell lung cancer (NSCLC) patients who underwent radiation or chemoradiation therapy. Kaplan-Meier survival curves showed that overall survival (OS) and disease-free survival (DFS) rates were significantly associated with two ATM SNPs, rs664143 and rs189037. Patients with the rs664143 GA or AA genotype had poorer DFS (hazard ratio (HR) = 1.40, 95% confidence interval (CI) = 1.05-1.86, P = 0.021) and OS (HR = 1.28, 95%CI = 1.12-1.78, P = 0.040) than those with the rs664143 GG phenotype. Patients with the rs189037 AG/GG genotypes had poorer prognoses than those with the rs189037 AA genotype (AG/GG vs. AA: DFS, HR = 1.44, 95%CI = 1.06-1.95, P=0.019; OS, HR = 1.16, 95%CI = 1.16-1.17-2.21, P=0.004). These results were confirmed by subgroup analysis based on clinical factors such as smoking, histology, tumor stage, treatment, and radiation dose, all of which were significantly associated with DFS and OS rates in NSCLC patients. These findings show that ATM rs664143 and rs189037 variants determine prognosis in NSCLC patients that have undergone radiation or chemoradiation therapies.

Keywords: ataxia telangiectasia mutated gene; non-small cell lung cancer; polymorphism; prognosis; radiation therapy.

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Case-Control Studies
  • DNA, Neoplasm / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis

Substances

  • DNA, Neoplasm
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins