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


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-β1-509C/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.
Zhang
Li
L
Department of Oncology, Huazhong University of Science and Technology, Wuhan, China.
Yang
Ming
M
Bi
Nan
N
Ji
Wei
W
Wu
Chen
C
Tan
Wen
W
Zhao
Lujun
L
Yu
Dianke
D
Lin
Dongxin
D
Wang
Luhua
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016009:Chi-Square Distribution; D003131:Combined Modality Therapy; D004947:Esophagus / Q000528:radiation effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011832:Radiation Injuries / Q000209:etiology* / Q000473:pathology; D011836:Radiation Tolerance / Q000235:genetics*; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D053773:Transforming Growth Factor beta1; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human