Research Paper Volume 12, Issue 8 pp 7465—7479

ATM gene polymorphisms are associated with poor prognosis of non-small cell lung cancer receiving radiation therapy

Junjun Mou 1, *, , Tao Hu 2, *, , Zhiwu Wang 3, *, , Wei Chen 4, , Yang Wang 1, , Wei Zhang 1, ,

  • 1 Department of Radiotherapy, Yantai Yuhuangding Hospital, The Affiliated Hospital of Qingdao University, Yantai 264000, Shandong, China
  • 2 Department of Thoracic Surgery, Yantai Yuhuangding Hospital, The Affiliated Hospital of Qingdao University, Yantai 264000, Shandong, China
  • 3 Department of Chemoradiotherapy, Tangshan People’s Hospital, Tangshan 063000, China
  • 4 Training Department, Yantai Yuhuangding Hospital, The Affiliated Hospital of Qingdao University, Yantai 264000, Shandong, China
* Equal contribution

received: December 1, 2019 ; accepted: March 30, 2020 ; published: April 24, 2020 ;

https://doi.org/10.18632/aging.103094
How to Cite

Copyright © 2020 Mou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We investigated the prognostic significance of ataxia telangiectasia mutated (ATM) single nucleotide polymorphisms (SNPs) in 720 Han Chinese non-small cell lung cancer (NSCLC) patients who underwent radiation or chemoradiation therapy. Kaplan-Meier survival curves showed that overall survival (OS) and disease-free survival (DFS) rates were significantly associated with two ATM SNPs, rs664143 and rs189037. Patients with the rs664143 GA or AA genotype had poorer DFS (hazard ratio (HR) = 1.40, 95% confidence interval (CI) = 1.05–1.86, P = 0.021) and OS (HR = 1.28, 95%CI = 1.12–1.78, P = 0.040) than those with the rs664143 GG phenotype. Patients with the rs189037 AG/GG genotypes had poorer prognoses than those with the rs189037 AA genotype (AG/GG vs. AA: DFS, HR = 1.44, 95%CI = 1.06–1.95, P=0.019; OS, HR = 1.16, 95%CI = 1.16–1.17–2.21, P=0.004). These results were confirmed by subgroup analysis based on clinical factors such as smoking, histology, tumor stage, treatment, and radiation dose, all of which were significantly associated with DFS and OS rates in NSCLC patients. These findings show that ATM rs664143 and rs189037 variants determine prognosis in NSCLC patients that have undergone radiation or chemoradiation therapies.

Abbreviations

ATM: Ataxia Telangiectasia Mutated; NSCLC: non-small cell lung cancer; SNP: single nucleotide polymorphism; HR: hazard ratio; CI: confidence interval; DFS: disease-free survival; OS: overall survival; CT: Computed Tomography; GTV: gross tumor volume; PET: Positron Emission Tomography; PCR: polymerase chain reaction; MST: median survival time.