Single Nucleotide Polymorphism at rs1800471:G915C of the Transforming Growth Factor 1 Gene is Associated with the Risk of Radiation Esophagitis in Patients with Lung Cancer

  • Zhuang Y
  • Lopez J
  • Gomez D
  • et al.
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Abstract

Purpose/Objective(s): In the setting of definitive radiation therapy for locally advanced non-small cell lung cancer (NSCLC), radiation esophagitis (RE) can be a severe toxicity. The significance of biologic markers such as transforming growth factor b1 (TGFbeta1) for predicting toxicity has been increasingly emphasized by recent investigations. We investigated the association between single nucleotide polymorphisms (SNPs) in the TGFbeta1 gene and the risk of RE in patients with NSCLC. Materials/Methods: The test data set consist of 97 NSCLC patients with available genomic DNA samples treated with radio(chemo)therapy from 2003 to 2006, when novel radiation techniques were implemented at MD Anderson. Eighty-two percent of patients had Stage III disease, 85% received platinum and taxane-based concurrent chemotherapy, and 98% received doses between 60 Gy and 72 Gy (median, 63 Gy; range, 54 to 72 Gy).We genotyped three SNPs of the TGFbeta1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by the polymerase chain reaction restriction fragment length polymorphism method. Cox proportional hazards analysis was performed to calculate the hazard ratio (HR) and confidence interval (CI) of each genotype on RE risk. Then, utilizing the same statistical method, 101 NSCLC patients treated with 3-dimensional conformal radio(chemo) therapy from 1998 to 2002 were used as a validation dataset. Results: In the test data set the incidence of RE Grade>2 was 90%. In univariate and multivariate analysis, the CG/CC genotype of TGFbeta1 rs1800471:G915C was associated with a statistically significantly higher risk of RE Grade > 2 ([HR] = 2.92; 95% CI, 1.61 - 5.29; p<0.001; Multivariate analysis, [HR] = 4.56; 95% CI, 1.87 - 11.07; p = 0.001) compared with the GG genotype. These results were then verified in the validation set, as the CG/CC genotype was again shown to be predictive of Grade > 2 RE in both univariate (HR = 2.42; p = 0.004) and multivariate (HR = 5.62; p<0.001) analysis. When the test dataset and validation dataset were analyzed as a whole, the results of the analysis were similar ([HR] = 2.57; p \ 0.001; Multivariate analysis, [HR] = 3.54; p<0.001). Additionally, patients with CG/CC genotypes for the combined test and validation sets who underwent concurrent chemoradiation had a higher RE incidence than patients with concurrent chemoradiation with GG genotypes (p<0.001). Conclusions: The CG/CC genotype of TGFbeta1 rs1800471:G915C gene is associated with a higher risk of RE in patients with NSCLC treated with definitive radio(chemo)therapy. This result was validated in a separate cohort of patients, suggesting the possibility of using this biomarker as a predictive factor for esophageal toxicity.

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Zhuang, Y., Lopez, J. L., Gomez, D., Wei, Q., Liu, Z., Wang, L., … Liao, Z. (2011). Single Nucleotide Polymorphism at rs1800471:G915C of the Transforming Growth Factor 1 Gene is Associated with the Risk of Radiation Esophagitis in Patients with Lung Cancer. International Journal of Radiation Oncology*Biology*Physics, 81(2), S195–S196. https://doi.org/10.1016/j.ijrobp.2011.06.352

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