title: Single-nucleotide polymorphisms of TGFβ1 and ATM associated with radiation-induced pneumonitis: a prospective cohort study of thoracic cancer patients in China.
abstract: BACKGROUND
  We examined the effects of the rs1800469 and rs1800470 single nucleotide polymorphisms (SNPs) of the transforming growth factor-β1 (TGFβ1) gene and the rs189037 and rs373759 SNPs of the ataxia telangiectasia mutated (ATM) gene on the risk of radiation-induced pneumonitis (RP) in patients who underwent radiotherapy for various thoracic malignancies.
  
  
  METHODS
  We determined the genotype and allele distributions of rs1800469 (C-509T), rs1800470 (C869T), rs189037 (A-111G), and rs373759 (126713 G>A) in 141 Han Chinese patients who underwent definitive thoracic radiotherapy (50 to 77 Gy, 5 days/wk) for lung cancer (small cell or non-small cell tumors, n = 97), esophageal squamous cell carcinoma (ESCC, n = 27), or mediastinal cancer (n = 17). Clinical variables were evaluated using multivariate logistic regression models to calculate the relative risk of RP associated with the clinical variables, and a Pearson correlation analysis was used to evaluate the relationship between the SNP genotypes and alleles and the incidence of RP for the various risk factors.
  
  
  RESULTS
  The T alleles of rs1800470 (CT/TT) and rs1800469 (CT/TT) and the G allele of rs189037 (GA/GG) were associated with the risk of ≥ grade-2 RP in the ESCC patients (P = 0.0006, P = 0.0127, and P = 0.0412, respectively), and that the A alleles of rs189037 (AG/AA) and rs373759 (AG/AA) were associated with the risk of ≥ grade-2 RP in the patients with mediastinal cancer (P = 0.0063 and P = 0.0003, respectively). None of the SNP genotypes were associated with the risk of RP in lung cancer patients.
  
  
  CONCLUSIONS
  The T alleles of the rs1800470 (CT/TT) and rs1800469 (CT/TT) SNPs of TGFβ1 and the G allele of the rs189037 (GA/GG) SNP of ATM are independent risk factors for RP in Chinese ESCC patients, and the A alleles of the rs189037 (AG/AA) and rs373759 (AG/AA) SNPs of ATM are independent risk factors for RP in Chinese patients with mediastinal cancer. These SNPs might represent useful biomarkers for personalizing radiotherapy regimens for Chinese patients with ESCC or mediastinal cancer to reduce the incidence of RP. Large-cohort studies of these SNPs in thoracic cancer patients are warranted.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Chongqing Medical University No. 1 Friendship Road, Yuanjiagang, Yuzhong District, Chongqing 400016, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Qianxia
authors.initials: Q
authors.lastname: Li
keywords: Radiation pneumonitis; ataxia telangiectasia mutated gene; single nucleotide polymorphism; transforming growth factor β1