ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.

Journal Article (Journal Article)

PURPOSE: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). METHODS AND MATERIALS: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. RESULTS: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. CONCLUSIONS: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

Full Text

Duke Authors

Cited Authors

  • Xiong, H; Liao, Z; Liu, Z; Xu, T; Wang, Q; Liu, H; Komaki, R; Gomez, D; Wang, L-E; Wei, Q

Published Date

  • March 15, 2013

Published In

Volume / Issue

  • 85 / 4

Start / End Page

  • 1066 - 1073

PubMed ID

  • 23154078

Pubmed Central ID

  • PMC3594431

Electronic International Standard Serial Number (EISSN)

  • 1879-355X

Digital Object Identifier (DOI)

  • 10.1016/j.ijrobp.2012.09.024


  • eng

Conference Location

  • United States