title: ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, China.
authors.forename: Huihua
authors.initials: H
authors.lastname: Xiong
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Qiming
authors.initials: Q
authors.lastname: Wang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: Daniel
authors.initials: D
authors.lastname: Gomez
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D064007:Ataxia Telangiectasia Mutated Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000208:ethnology / Q000235:genetics* / Q000532:radiotherapy*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017564:Radiation Pneumonitis / Q000208:ethnology / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044465:White People
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases