Association between single nucleotide polymorphisms of the transforming growth factor β1 gene and the risk of severe radiation esophagitis in patients with lung cancer

Radiother Oncol. 2012 Dec;105(3):299-304. doi: 10.1016/j.radonc.2012.08.014. Epub 2012 Sep 27.

Abstract

Purpose: We investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor β1 (TGFβ1) gene and the risk of radiation-induced esophageal toxicity (RE) in patients with non-small-cell lung cancer (NSCLC).

Methods and materials: Ninety-seven NSCLC patients with available genomic DNA samples and mostly treated with intensity modulated radio(chemo)therapy from 2003 to 2006 were used as a test dataset and 101 NSCLC patients treated with 3-dimensional conformal radio(chemo)therapy from 1998 to 2002 were used as a validation set. We genotyped three SNPs of the TGFβ1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by the polymerase chain reaction restriction fragment length polymorphism method.

Results: In the test dataset, the CT/TT genotypes of TGFβ1 rs1800469:C-509T were associated with a statistically significant higher risk of RE grade⩾3 in univariate (P=0.026) and multivariate analysis (P=0.045) when compared with the CC genotype. These results were again observed in both univariate (P=0.045) and multivariate (P=0.023) analysis in the validation dataset.

Conclusion: We found and validated that the TGFβ1 rs1800469:C-509T genotype is associated with severe RE. This response marker may be used for guiding therapy intensity in an individual patient, which would further the goal of individualized therapy.

Publication types

  • Validation Study

MeSH terms

  • Analysis of Variance
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Chemotherapy, Adjuvant
  • Esophagitis / diagnosis
  • Esophagitis / etiology
  • Esophagitis / genetics*
  • Female
  • Genetic Markers / genetics
  • Genotype
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Predictive Value of Tests
  • Radiotherapy, Adjuvant / adverse effects*
  • Reproducibility of Results
  • Risk
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Transforming Growth Factor beta1 / genetics*

Substances

  • Genetic Markers
  • Transforming Growth Factor beta1