HSPB1 gene polymorphisms predict risk of mortality for US patients after radio(chemo)therapy for non-small cell lung cancer

Int J Radiat Oncol Biol Phys. 2012 Oct 1;84(2):e229-35. doi: 10.1016/j.ijrobp.2012.03.032. Epub 2012 May 19.

Abstract

Purpose: We investigated potential associations between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and overall survival in US patients with non-small cell lung cancer (NSCLC).

Methods and materials: Using available genomic DNA samples from 224 patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped 2 SNPs of HSPB1 (NCBI SNP nos. rs2868370 and rs2868371). We used both Kaplan-Meier cumulative probability and Cox proportional hazards analyses to evaluate the effect of HSPB1 genotypes on survival.

Results: Our cohort consisted of 117 men and 107 women, mostly white (79.5%), with a median age of 70 years. The median radiation dose was 66 Gy (range, 63-87.5 Gy), and 183 patients (82%) received concurrent platinum-based chemotherapy. The most common genotype of the rs2868371 SNP was CC (61%). Univariate and multivariate analyses showed that this genotype was associated with poorer survival than CG and GG genotypes (univariate hazard ratio [HR] = 1.39, 95% confidence interval [CI], 1.02-1.90; P=.037; multivariate HR = 1.39; 95% CI, 1.01-1.92; P=.045).

Conclusions: Our results showed that the CC genotype of HSPB1 rs2868371 was associated with poorer overall survival in patients with NSCLC after radio(chemo)therapy, findings that contradict those of a previous study of Chinese patients. Validation of our findings with larger numbers of similar patients is needed, as are mechanical and clinical studies to determine the mechanism underlying these associations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Chemoradiotherapy / mortality
  • Female
  • Genotype
  • HSP27 Heat-Shock Proteins / genetics*
  • Humans
  • Induction Chemotherapy / methods
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Probability
  • Proportional Hazards Models
  • Radiotherapy Dosage
  • Reproducibility of Results
  • Risk
  • Survival Analysis
  • United States

Substances

  • HSP27 Heat-Shock Proteins
  • Neoplasm Proteins