A Study of Ethnic Differences in TGFβ1 Gene Polymorphisms and Effects on the Risk of Radiation Pneumonitis in Non–Small-Cell Lung Cancer

Abstract

To investigate whether Chinese non-small-cell lung cancer (NSCLC) patients with risk of radiation pneumonitis (RP) (grade ≥ 3) caused by radiotherapy display reliable single-nucleotide polymorphism (SNP) marker(s) located on the transforming growth factor-beta-1 (TGFβ1) gene. DNA was isolated from blood samples obtained from NSCLC patients (n = 167) treated with radiotherapy alone (n = 23) or chemoradiation (n = 144) with the median total radiation dose of 56 Gy between 2007 and 2010. A comprehensive approach toward characterizing the TGFβ1 SNPs in Chinese patients was carried out in this study. Eight SNPs of the TGFβ1 gene (rs1800469, rs1800471, rs1982073, rs4803455, rs11466345, rs12983047, rs10417924, and rs10980942) were finally genotyped by the direct DNA sequencing method. Kaplan-Meier cumulative probability was used to assess the risk of RP of grade 3 or higher. Cox proportional hazard analysis was used to evaluate the effect of TGFβ1 genotypes on RP risk. A total of 46 patients (27.5%) developed RP of grade 3 or higher, based on Common Terminology Criteria for Adverse Events version 3.0, with a median follow-up of 29.5 months (range, 16-58). The rs1982073 SNP, associated with RP risk in whites, was not found to be associated with the risk of RP of grade 3 or higher in Chinese NSCLC patients. Multivariate analysis found AG/GG genotypes of the novel TGFβ1 SNP rs11466345 to be associated with a significantly higher risk of RP of grade 3 or higher compared with the AA genotypes, after adjustment for age, smoking status, and dosimetric parameters (for mean lung dose, adjusted hazards ratio = 2.295, 95% confidence interval: 1.101-4.783, p = 0.027; for volume of normal lung receiving 20 GY or more radiation, adjusted hazards ratio = 2.142, 95% confidence interval: 1.033-4.441, p = 0.041). The AG/GG genotypes of novel TGFβ1 rs11466345 were associated with a higher risk of RP in Chinese NSCLC patients treated with radiotherapy. The rs1982073 SNP, associated with RP risk in whites, was not correlated with higher RP risk in the Chinese patients studied. Further studies are warranted to confirm these findings in different ethnic populations.