Single Nucleotide Polymorphism at rs1982073:T869C of the TGFβ1 Gene Is Associated With the Risk of Radiation Pneumonitis in Patients With Non–Small-Cell Lung Cancer Treated With Definitive Radiotherapy
- 10 July 2009
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 27 (20), 3370-3378
- https://doi.org/10.1200/jco.2008.20.6763
Abstract
In search of reliable biologic markers to predict the risk of normal tissue damage by radio(chemo)therapy before treatment, we investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor 1 (TGFβ1) gene and risk of radiation pneumonitis (RP) in patients with non–small-cell lung cancer (NSCLC). Using 164 available genomic DNA samples from patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped three SNPs of the TGFβ1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by polymerase chain reaction restriction fragment length polymorphism method. We used Kaplan-Meier cumulative probability to assess the risk of grade ≥ 3 RP and Cox proportional hazards analyses to evaluate the effect of TGFβ1 genotypes on such risk. There were 90 men and 74 women in the study, with median age of 63 years. Radiation doses ranging from 60 to 70 Gy (median = 63 Gy) in 30 to 58 fractions were given to 158 patients (96.3%) and platinum-based chemotherapy to 147 (89.6%). Grade ≥ 2 and grade ≥ 3 RP were observed in 74 (45.1%) and 36 patients (22.0%), respectively. Multivariate analysis found CT/CC genotypes of TGFβ1 rs1982073:T869C to be associated with a statistically significantly lower risk of RP grades ≥ 2 (hazard ratio [HR] = 0.489; 95% CI, 0.227 to 0.861; P = .013) and grades ≥ 3 (HR = 0.390; 95% CI, 0.197 to .774; P = 0.007), respectively, compared with the TT genotype, after adjustment for Karnofsky performance status, smoking status, pulmonary function, and dosimetric parameters. Our results showed that CT/CC genotypes of TGFβ1 rs1982073:T869C gene were associated with lower risk of RP in patients with NSCLC treated with definitive radio(chemo)therapy and thus may serve as a reliable predictor of RP.Keywords
This publication has 48 references indexed in Scilit:
- Analysis of Radiation Pneumonitis Risk Using a Generalized Lyman ModelInternational Journal of Radiation Oncology*Biology*Physics, 2008
- TGF-β: A Master of All T Cell TradesCell, 2008
- Association of Genetic Variation in the Transforming Growth Factor β-1 Gene with Serum Levels and Risk of Colorectal NeoplasiaCancer Research, 2008
- The late radiotherapy normal tissue injury phenotypes of telangiectasia, fibrosis and atrophy in breast cancer patients have distinct genotype-dependent causesBritish Journal of Cancer, 2007
- Does transforming growth factor-β1 predict for radiation-induced pneumonitis in patients treated for lung cancer?Cytokine, 2006
- A molecular mechanism for the differential regulation of TGF-β1 expression due to the common SNP −509C-T (c. −1347C > T)Human Genetics, 2006
- Transforming growth factor-β plasma dynamics and post-irradiation lung injury in lung cancer patientsRadiotherapy and Oncology, 2004
- Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patientsInternational Journal of Radiation Biology, 2003
- Role of Transforming Growth Factor β in Human DiseaseThe New England Journal of Medicine, 2000
- REGULATION OF IMMUNE RESPONSES BY TGF-βAnnual Review of Immunology, 1998