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

Zhipeng Yan,Xue Yang,Xin Yang,Min Bai,Xiang Tong,Hong Fan,Lingjing Yang,Sitong Liu,Yao Ma

doi:10.1186/s12890-017-0555-7

Abstract

BackgroundPrevious 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.MethodsA 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.ResultsTen 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.ConclusionsThe 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.

Highlights

Previous studies have suggested that Deoxyribonucleic acid (DNA) double-strand break (DSB) repair is an important protective pathway after damage
Eligible studies We searched the PubMed, Embase, China National Knowledge Internet (CNKI) and Wanfang databases to identify studies that investigated the association between ataxia telangiectasia mutated (ATM) gene polymorphisms and lung cancer as or radiation-induced pneumonitis (RP) in lung cancer patients treated with radiotherapy using the following search terms: “ATM” and “cancer” or “lung cancer” or “Lung Neoplasms” and “polymorphism” or “variant”; “ATM” and “radiation pneumonia” or “radiation pneumonitis” and “polymorphism” or “variant”
The following were the inclusion criteria for studies in our meta-analysis: (1) case-control studies focused on ATM polymorphisms and lung cancer susceptibility or RP risk, (2) data on genotype frequencies were available for both the cases and controls, (3) published in English or Chinese, and (4) the genotype distribution of the control group was in accordance with Hardy-Weinberg equilibrium

Summary

Introduction

Previous studies have suggested that DNA double-strand break (DSB) repair is an important protective pathway after damage. Smoking is a major risk factor for lung cancer, only 15% of smokers develop lung cancer [2, 3], suggesting that different populations are more or less susceptible to carcinogens and that genetic factors probably play an important role in cancer aetiologies [4]. Its risk factors include patient-related factors, such as gender, smoking and pulmonary function, and treatment-related factors, such as the radiation dose and irradiated lung volume, and whether surgery or chemotherapy was performed [9,10,11]. These factors do not sufficiently explain the wide variations observed in susceptibility among patients. Recent studies have shown that variation in individual susceptibility to cancers and RP is affected by gene polymorphisms, especially those affect DNA repair [12]

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Discussion

Conclusion