title: Functional promoter variant rs2868371 of HSPB1 is associated with risk of radiation pneumonitis after chemoradiation for non-small cell lung cancer.
abstract: OBJECTIVE
  To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk.
  
  
  RESULTS
  Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic.
  
  
  CONCLUSIONS
  The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 97, Houston, TX 77030, USA.
authors: Qingsong
authors: Q
authors: Pang
authors: Qingyi
authors: Q
authors: Wei
authors: Ting
authors: T
authors: Xu
authors: Xianglin
authors: X
authors: Yuan
authors: Jose Luis
authors: JL
authors: Lopez Guerra
authors: Lawrence B
authors: LB
authors: Levy
authors: Zhensheng
authors: Z
authors: Liu
authors: Daniel R
authors: DR
authors: Gomez
authors: Yan
authors: Y
authors: Zhuang
authors: Li-E
authors: LE
authors: Wang
authors: Radhe
authors: R
authors: Mohan
authors: Ritsuko
authors: R
authors: Komaki
authors: Zhongxing
authors: Z
authors: Liao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000628:therapy; D005260:Female; D005838:Genotype; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017564:Radiation Pneumonitis / Q000235:genetics* / Q000473:pathology; D011836:Radiation Tolerance / Q000235:genetics*; D011879:Radiotherapy Dosage; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones