Dataset Information

Single nucleotide polymorphism at rs1982073:T869C of the TGFbeta 1 gene is associated with the risk of radiation pneumonitis in patients with non-small-cell lung cancer treated with definitive radiotherapy.

ABSTRACT:

Purpose

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 (TGFbeta1) gene and risk of radiation pneumonitis (RP) in patients with non-small-cell lung cancer (NSCLC).

Patients and methods

Using 164 available genomic DNA samples from patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped three SNPs of the TGFbeta1 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 > or = 3 RP and Cox proportional hazards analyses to evaluate the effect of TGFbeta1 genotypes on such risk.

Results

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 > or = 2 and grade > or = 3 RP were observed in 74 (45.1%) and 36 patients (22.0%), respectively. Multivariate analysis found CT/CC genotypes of TGFbeta1 rs1982073:T869C to be associated with a statistically significantly lower risk of RP grades > or = 2 (hazard ratio [HR] = 0.489; 95% CI, 0.227 to 0.861; P = .013) and grades > or = 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.

Conclusion

Our results showed that CT/CC genotypes of TGFbeta1 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.

SUBMITTER: Yuan X

PROVIDER: S-EPMC4385796 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Publications

Single nucleotide polymorphism at rs1982073:T869C of the TGFbeta 1 gene is associated with the risk of radiation pneumonitis in patients with non-small-cell lung cancer treated with definitive radiotherapy.

Yuan Xianglin X Liao Zhongxing Z Liu Zhensheng Z Wang Li-E LE Tucker Susan L SL Mao Li L Wang Xin Shelley XS Martel Mary M Komaki Ritsuko R Cox James D JD Milas Luka L Wei Qingyi Q

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20090420 20

<h4>Purpose</h4>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 (TGFbeta1) gene and risk of radiation pneumonitis (RP) in patients with non-small-cell lung cancer (NSCLC).<h4>Patients and methods</h4>Using 164 available genomic DNA samples from patients with NSCLC treated with definitive radio(chemo)therapy, ...[more]

PMID: 19380441

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Project description:BackgroundRadiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT).MethodsAmong consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ≥6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis.ResultsFive hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ≥ grade 2 and ≥ grade 3 were significantly lower in CAM-era (grade ≥2, 16% vs. 9.6%, P=0.047; grade ≥3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ≥ grade 3 was significantly lower, and that of grade ≥2 had a lower tendency (grade ≥3, 7.2% vs. 0%, P=0.011; grade ≥2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ≥ grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ≥ grade 2 and ≥ grade 3.ConclusionsCAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be conﬁrmed in prospective studies.

Dataset Information

Single nucleotide polymorphism at rs1982073:T869C of the TGFbeta 1 gene is associated with the risk of radiation pneumonitis in patients with non-small-cell lung cancer treated with definitive radiotherapy.

Purpose

Patients and methods

Results

Conclusion

Publications

Single nucleotide polymorphism at rs1982073:T869C of the TGFbeta 1 gene is associated with the risk of radiation pneumonitis in patients with non-small-cell lung cancer treated with definitive radiotherapy.

Similar Datasets

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