title: Functional promoter rs2868371 variant of HSPB1 associates with radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with radio(chemo)therapy.
abstract: OBJECTIVE
  We investigated the association between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and the risk of radiation-induced esophageal toxicity (RIET) in patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  The experimental dataset comprised 120 NSCLC patients who were treated with radio(chemo)therapy between 2005 and 2009, when novel radiation techniques were implemented at MD Anderson. The validation dataset comprised 181 NSCLC patients treated between 1998 and 2004. We genotyped two SNPs of the HSPB1 gene (rs2868370 and rs2868371) by TaqMan assay.
  
  
  RESULTS
  Univariate and multivariate analyses of the experimental dataset showed that the CG/GG genotypes of HSPB1 rs2868371 were associated with significantly lower risk of grade ⩾3 RIET than the CC genotype (univariate hazard ratio [HR] 0.30; 95% confidence interval [CI], 0.10-0.91; P=0.033; multivariate HR 0.29; 95% CI, 0.09-0.97; P=0.045). This difference in risk was replicated in the validation cohort despite the different radiation techniques used during that period.
  
  
  CONCLUSIONS
  The CG/GG genotypes of HSPB1 rs2868371 were associated with lower risk of RIET, compared with the CC genotype in patients with NSCLC treated with radio(chemo)therapy. This finding should be validated in large multi-institutional prospective trials.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, USA.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Lopez Guerra
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
authors.forename: Daniel
authors.initials: D
authors.lastname: Gomez
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
authors.forename: Minghuan
authors.initials: M
authors.lastname: Li
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D016009:Chi-Square Distribution; D004947:Esophagus / Q000528:radiation effects*; 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; D012307:Risk Factors
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones