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Impact of single-nucleotide polymorphisms on radiation pneumonitis in cancer patients.

ABSTRACT: Radiation pneumonitis (RP) is one of the most important dose-limiting toxicities in the radiotherapy of thoracic tumors, which reduces the rate of local tumor control and overall survival and severely affects the patients' quality of life. Single-nucleotide polymorphisms (SNPs) have recently attracted increasing attention as biomarkers for predicting the development of RP. SNPs in inflammation-related, DNA repair-related, stress response-related and angiogenesis-related genes were proved to be associated with RP, with different underlying mechanisms. Radiogenomics focuses on the differences in radiosensitivity caused by gene sequence variation, which may prove helpful in investigating the abovementioned associations. In this review, we aimed to investigate the associations between RP and SNPs reported in recent studies and highlight the main content and prospects of radiogenomics.

SUBMITTER: Guo CX

PROVIDER: S-EPMC4727127 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Impact of single-nucleotide polymorphisms on radiation pneumonitis in cancer patients.

Guo Cheng-Xian CX Wang Jing J Huang Li-Hua LH Li Jin-Gao JG Chen Xiang X

Molecular and clinical oncology 20151030 1

Radiation pneumonitis (RP) is one of the most important dose-limiting toxicities in the radiotherapy of thoracic tumors, which reduces the rate of local tumor control and overall survival and severely affects the patients' quality of life. Single-nucleotide polymorphisms (SNPs) have recently attracted increasing attention as biomarkers for predicting the development of RP. SNPs in inflammation-related, DNA repair-related, stress response-related and angiogenesis-related genes were proved to be a ...[more]

PMID: 26870349

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Project description:BACKGROUND:We examined the effects of the rs1800469 and rs1800470 single nucleotide polymorphisms (SNPs) of the transforming growth factor-?1 (TGF?1) gene and the rs189037 and rs373759 SNPs of the ataxia telangiectasia mutated (ATM) gene on the risk of radiation-induced pneumonitis (RP) in patients who underwent radiotherapy for various thoracic malignancies. METHODS:We determined the genotype and allele distributions of rs1800469 (C-509T), rs1800470 (C869T), rs189037 (A-111G), and rs373759 (126713 G>A) in 141 Han Chinese patients who underwent definitive thoracic radiotherapy (50 to 77 Gy, 5 days/wk) for lung cancer (small cell or non-small cell tumors, n = 97), esophageal squamous cell carcinoma (ESCC, n = 27), or mediastinal cancer (n = 17). Clinical variables were evaluated using multivariate logistic regression models to calculate the relative risk of RP associated with the clinical variables, and a Pearson correlation analysis was used to evaluate the relationship between the SNP genotypes and alleles and the incidence of RP for the various risk factors. RESULTS:The T alleles of rs1800470 (CT/TT) and rs1800469 (CT/TT) and the G allele of rs189037 (GA/GG) were associated with the risk of ? grade-2 RP in the ESCC patients (P = 0.0006, P = 0.0127, and P = 0.0412, respectively), and that the A alleles of rs189037 (AG/AA) and rs373759 (AG/AA) were associated with the risk of ? grade-2 RP in the patients with mediastinal cancer (P = 0.0063 and P = 0.0003, respectively). None of the SNP genotypes were associated with the risk of RP in lung cancer patients. CONCLUSION:The T alleles of the rs1800470 (CT/TT) and rs1800469 (CT/TT) SNPs of TGF?1 and the G allele of the rs189037 (GA/GG) SNP of ATM are independent risk factors for RP in Chinese ESCC patients, and the A alleles of the rs189037 (AG/AA) and rs373759 (AG/AA) SNPs of ATM are independent risk factors for RP in Chinese patients with mediastinal cancer. These SNPs might represent useful biomarkers for personalizing radiotherapy regimens for Chinese patients with ESCC or mediastinal cancer to reduce the incidence of RP. Large-cohort studies of these SNPs in thoracic cancer patients are warranted.

Project description:IntroductionThis study investigated the clinical characteristics and predictive factors for developing acute extended radiation pneumonitis with a focus on the presence and radiological characteristics of preexisting interstitial lung disease.MethodsOf 1429 irradiations for lung cancer from May 2006 to August 2013, we reviewed 651 irradiations involving the lung field. The presence, compatibility with usual interstitial pneumonia, and occupying area of preexisting interstitial lung disease were retrospectively evaluated by pretreatment computed tomography. Cases of non-infectious, non-cardiogenic, acute respiratory failure with an extended bilateral shadow developing within 30 days after the last irradiation were defined as acute extended radiation pneumonitis.ResultsNine (1.4%) patients developed acute extended radiation pneumonitis a mean of 6.7 days after the last irradiation. Although preexisting interstitial lung disease was found in 13% of patients (84 patients), 78% of patients (7 patients) with acute extended radiation pneumonitis cases had preexisting interstitial lung disease, which resulted in incidences of acute extended radiation pneumonitis of 0.35 and 8.3% in patients without and with preexisting interstitial lung disease, respectively. Multivariate logistic analysis indicated that the presence of preexisting interstitial lung disease (odds ratio = 22.6; 95% confidence interval = 5.29-155; p < 0.001) and performance status (≥2; odds ratio = 4.22; 95% confidence interval = 1.06-20.8; p = 0.049) were significant predictive factors. Further analysis of the 84 patients with preexisting interstitial lung disease revealed that involvement of more than 10% of the lung field was the only independent predictive factor associated with the risk of acute extended radiation pneumonitis (odds ratio = 6.14; 95% confidence interval = 1.0-37.4); p = 0.038).ConclusionsPretreatment computed tomography evaluations of the presence of and area size occupied by preexisting interstitial lung disease should be assessed for safer irradiation of areas involving the lung field.

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Impact of single-nucleotide polymorphisms on radiation pneumonitis in cancer patients.

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Impact of single-nucleotide polymorphisms on radiation pneumonitis in cancer patients.

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