Background: 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 (TGF beta 1) gene. Methods: 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 TGF beta 1 SNPs in Chinese patients was carried out in this study. Eight SNPs of the TGF beta 1 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 TGF beta 1 genotypes on RP risk. Results: 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 TGF beta 1 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). Conclusion: The AG/GG genotypes of novel TGF beta 1 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.
[1]Shanghai Jiao Tong Univ, Dept Shanghai Lung Canc Ctr, Shanghai Chest Hosp, Shanghai 200030, Peoples R China.
[2]Shanghai Jiao Tong Univ, Dept Radiat Oncol, Shanghai Chest Hosp, Shanghai 200030, Peoples R China.
[3]Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China.
[4]Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Beijing 100864, Peoples R China.
[5]Shanghai Jiao Tong Univ, BioX Ctr, Shanghai 200030, Peoples R China.
(8.0+极速模式)