Association of TGF-β1 and XPD polymorphisms with severe acute radiation-induced esophageal toxicity in locally advanced lung cancer patients treated with radiotherapy

Purpose: Radiation-induced esophageal toxicity (RIET) is a dose-limiting toxicity in lung cancer patients receiving radiotherapy. Accumulating evidence indicates that DNA repair and the cytokine pathways play essential roles in radiation-induced diseases. Genetic polymorphisms of genes in these pathways may affect gene function and/or gene expression and lead to different treatment-related esophageal toxicity. Materials and methods: This study investigated the association of 21 polymorphisms in 14 genes, with the occurrence of >= grade 2 acute RIET. Genotypes were analyzed among 213 stage III lung cancer patients receiving radiotherapy. Results: We used Cox proportional hazard model to examine the effects of genotypes on >= grade 2 acute RIET risk and Kaplan-Meier estimator to compare effects of different genotypes on such risk. Multivariate analysis showed that CT or TT genotype of TGF-beta 1-509C/T polymorphism was associated with a significantly higher RIET risk (adjusted hazard ratio [HR] = 2.47; 95% confidence interval (CI) = 1.17-5.24; P = 0.018, or HR = 3.86; 95% CI = 1.50-9.92; P = 0.005), respectively, compared with the CC genotype. Moreover, Lys/Gln+Gln/Gln genotypes of XPD Lys751Gln polymorphism were also associated with a significantly decreased RIET risk (adjusted HR = 0.55; 95% CI = 0.32-0.96; P = 0.030). Conclusions: This report, for the first time, examined the influence of inherited variation in the DNA repair and the cytokine pathways on RIET. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 97 (2010) 19-25