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

Abstract

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-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.

• Authors: Li Zhang, Ming Yang, Nan Bi, Wei Ji, Chen Wu, Wen Tan, Lujun Zhao, Dianke Yu, Dongxin Lin, Luhua Wang
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 97 Issue 1 Pg. 19-25 (Oct 2010) ISSN: 1879-0887 [Electronic] Ireland
• PMID: 20832885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Transforming Growth Factor beta1
• Xeroderma Pigmentosum Group D Protein
• ERCC2 protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chi-Square Distribution
• Combined Modality Therapy
• Esophagus (radiation effects)
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology, radiotherapy)
• Male
• Middle Aged
• Neoplasm Staging
• Polymorphism, Genetic
• Proportional Hazards Models
• Prospective Studies
• Radiation Injuries (etiology, pathology)
• Radiation Tolerance (genetics)
• Radiotherapy, Conformal (adverse effects)
• Transforming Growth Factor beta1 (genetics)
• Xeroderma Pigmentosum Group D Protein (genetics)