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Association between ATM gene polymorphisms, lung cancer susceptibility and radiation-induced pneumonitis: a meta-analysis.

ABSTRACT: Previous studies have suggested that DNA double-strand break (DSB) repair is an important protective pathway after damage. The ataxia telangiectasia mutated (ATM) gene plays an important role in the DNA DSB repair pathway. DNA damage is a major cytotoxic effect that can be caused by radiation, and the ability to repair DNA after damage varies among different tissues. Impaired DNA repair pathways are associated with high sensitivity to radiation exposure. Hence, ATM gene polymorphisms are thought to influence the risk of cancer and radiation-induced pneumonitis (RP) risk in cancer patients treated with radiotherapy. However, the results of previous studies are inconsistent. We therefore conducted this comprehensive meta-analysis.A systematic literature search was performed in the PubMed, Embase, China National Knowledge Internet (CNKI) and Wanfang databases to identify studies that investigated the association between the ATM gene polymorphisms and both lung cancer and RP radiotherapy-treated lung cancer (the last search was conducted on Dec.10, 2015). The odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of these relationships. Funnel plots and Begg's and Egger's tests were conducted to assess the publication bias. All analyses were performed in STATA 13.0 software.Ten eligible case-control studies (4731 cases and 5142 controls) on lung cancer susceptibility and four (192 cases and 772 controls) on RP risk were included. The results of the overall and subgroup analyses indicated that in the ATM gene, the rs189037 (-111G?>?A, -4519G?>?A), rs664677 (44831C?>?T, 49238C?>?T) and rs664143 (131,717 T?>?G) polymorphisms were significantly associated with lung cancer susceptibility (OR?=?1.21, 95% CI?=?1.04-1.39, P?=?0.01; OR?=?1.26, 95% CI?=?1.06-1.49, P?=?0.01; OR?=?1.43, 95% CI?=?1.15-1.78, P?

SUBMITTER: Yan Z

PROVIDER: S-EPMC5731205 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Association between ATM gene polymorphisms, lung cancer susceptibility and radiation-induced pneumonitis: a meta-analysis.

Yan Zhipeng Z Tong Xiang X Ma Yao Y Liu Sitong S Yang Lingjing L Yang Xin X Yang Xue X Bai Min M Fan Hong H

BMC pulmonary medicine 20171215 1

<h4>Background</h4>Previous studies have suggested that DNA double-strand break (DSB) repair is an important protective pathway after damage. The ataxia telangiectasia mutated (ATM) gene plays an important role in the DNA DSB repair pathway. DNA damage is a major cytotoxic effect that can be caused by radiation, and the ability to repair DNA after damage varies among different tissues. Impaired DNA repair pathways are associated with high sensitivity to radiation exposure. Hence, ATM gene polymo ...[more]

PMID: 29246212

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Project description:BackgroundWe examined the effects of the rs1800469 and rs1800470 single nucleotide polymorphisms (SNPs) of the transforming growth factor-β1 (TGFβ1) 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.MethodsWe 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.ResultsThe 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.ConclusionThe T alleles of the rs1800470 (CT/TT) and rs1800469 (CT/TT) SNPs of TGFβ1 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.

Dataset Information

Association between ATM gene polymorphisms, lung cancer susceptibility and radiation-induced pneumonitis: a meta-analysis.

Publications

Association between ATM gene polymorphisms, lung cancer susceptibility and radiation-induced pneumonitis: a meta-analysis.

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