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

Wei Zhang,Wei Chen,Zhiwu Wang,Tao Hu,Junjun Mou,Yang Wang

doi:10.18632/aging.103094

Wei Zhang, Wei Chen + Show 4 more

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https://doi.org/10.18632/aging.103094

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Journal: Aging	Publication Date: Apr 24, 2020
Citations: 3	License type: cc-by

Affiliation: Yuhuangding Hospital, Tangshan People's Hospital

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.

Highlights

Lung cancer is one of the leading causes of cancer mortality worldwide, with nearly 2.1 million new lung cancer cases and 1.8 million lung cancer deaths reported in 2018 [1]
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
We assessed the association between four ATM SNPs and the survival outcomes in NSCLC patients of Han Chinese origin who received radiation therapy alone or chemo-radiation therapy

Summary

Introduction

Lung cancer is one of the leading causes of cancer mortality worldwide, with nearly 2.1 million new lung cancer cases and 1.8 million lung cancer deaths reported in 2018 [1]. In China, the incidence of lung cancer has increased by 26.9% annually, and the numbers of lung cancer patients have doubled every 10 to 15 years in the last 50 years [3]. In the last three decades, the mortality rate of lung cancer has increased by 465%, and replaced liver cancer as the most common malignant tumor in China [4]. The two main categories of lung cancer are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC); NSCLC accounts for nearly 87% of all lung cancer cases, about 75% of which are diagnosed in the advanced stages with poor prognosis [5]. The prognostic indicators in NSCLC patients include TNM stage [11], serum levels of tumor www.aging-us.com markers [12], tumor size [13], blood glucose levels, and treatment modalities [14, 15]

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