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ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.

ABSTRACT: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP).We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered.Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ?3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites.ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

SUBMITTER: Xiong H

PROVIDER: S-EPMC3594431 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.

Xiong Huihua H Liao Zhongxing Z Liu Zhensheng Z Xu Ting T Wang Qiming Q Liu Hongliang H Komaki Ritsuko R Gomez Daniel D Wang Li-E LE Wei Qingyi Q

International journal of radiation oncology, biology, physics 20121112 4

<h4>Purpose</h4>The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP).<h4>Methods and materials</h4>We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumula ...[more]

PMID: 23154078

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Project description: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?<?0.01). Additionally, the rs189037 variant was significantly associated with RP risk (OR?=?1.74, 95% CI?=?1.02-2.97, P?=?0.04). No publication bias was found in the funnel plots, Begg's tests or Egger's tests.The results indicate that the ATM rs189037, rs664677 and rs664143 gene polymorphisms are risk factors for lung cancer, while the ATM rs189037 variant was significantly associated with RP risk.

Dataset Information

ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.

Publications

ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.

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