title: Single nucleotide polymorphism at rs1982073:T869C of the TGFbeta 1 gene is associated with the risk of radiation pneumonitis in patients with non-small-cell lung cancer treated with definitive radiotherapy.
abstract: OBJECTIVE
  In search of reliable biologic markers to predict the risk of normal tissue damage by radio(chemo)therapy before treatment, we investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor 1 (TGFbeta1) gene and risk of radiation pneumonitis (RP) in patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Using 164 available genomic DNA samples from patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped three SNPs of the TGFbeta1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by polymerase chain reaction restriction fragment length polymorphism method. We used Kaplan-Meier cumulative probability to assess the risk of grade > or = 3 RP and Cox proportional hazards analyses to evaluate the effect of TGFbeta1 genotypes on such risk.
  
  
  RESULTS
  There were 90 men and 74 women in the study, with median age of 63 years. Radiation doses ranging from 60 to 70 Gy (median = 63 Gy) in 30 to 58 fractions were given to 158 patients (96.3%) and platinum-based chemotherapy to 147 (89.6%). Grade > or = 2 and grade > or = 3 RP were observed in 74 (45.1%) and 36 patients (22.0%), respectively. Multivariate analysis found CT/CC genotypes of TGFbeta1 rs1982073:T869C to be associated with a statistically significantly lower risk of RP grades > or = 2 (hazard ratio [HR] = 0.489; 95% CI, 0.227 to 0.861; P = .013) and grades > or = 3 (HR = 0.390; 95% CI, 0.197 to .774; P = 0.007), respectively, compared with the TT genotype, after adjustment for Karnofsky performance status, smoking status, pulmonary function, and dosimetric parameters.
  
  
  CONCLUSIONS
  Our results showed that CT/CC genotypes of TGFbeta1 rs1982073:T869C gene were associated with lower risk of RP in patients with NSCLC treated with definitive radio(chemo)therapy and thus may serve as a reliable predictor of RP.
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tucker
authors.forename: Li
authors.initials: L
authors.lastname: Mao
authors.forename: Xin Shelley
authors.initials: XS
authors.lastname: Wang
authors.forename: Mary
authors.initials: M
authors.lastname: Martel
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Luka
authors.initials: L
authors.lastname: Milas
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D017564:Radiation Pneumonitis / Q000209:etiology* / Q000235:genetics; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1