Open AccessFunctional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small‐cell lung cancer
Author(s) -
Lopez Guerra Jose Luis,
Song YiPeng,
Nguyen QuynhNhu,
Gomez Daniel R.,
Liao Zhongxing,
Xu Ting
Publication year - 2018
Publication title -
chronic diseases and translational medicine
Language(s) - English
Resource type - Journals
ISSN - 2589-0514
DOI - 10.1016/j.cdtm.2018.02.006
Subject(s) - medicine , dlco , lung cancer , radiation therapy , univariate analysis , single nucleotide polymorphism , diffusing capacity , pulmonary function testing , oncology , gastroenterology , lung , genotype , multivariate analysis , lung function , biology , gene , biochemistry
Objective Single‐nucleotide polymorphisms (SNPs) in the ataxia telangiectasia–mutated gene ATM have been linked with pneumonitis after radiotherapy for lung cancer but have not been evaluated in terms of pulmonary function impairment. Here we investigated potential associations between SNPs in ATM and changes in diffusing capacity of the lung for carbon monoxide (DLCO) in patients with non–small‐cell lung cancer (NSCLC) after radiotherapy. Methods From November 1998 through June 2009, 448 consecutive patients with inoperable primary NSCLC underwent definitive (≥60 Gy) radiotherapy, with or without chemotherapy. After excluding patients with a history of thoracic surgery, radiation, or lung cancer; without DNA samples available for analysis; or without pulmonary function testing within the 12 months before and the 12 months after radiotherapy, 100 patients were identified who are the subjects of this study. We genotyped two SNPs of ATM previously found to be associated with radiation‐induced pneumonitis (rs189037 and rs228590) and evaluated potential correlations between these SNPs and impairment (decreases) in DLCO by using logistic regression analysis. Results Univariate and multivariate analyses showed that the AA genotype of ATM rs189037 was associated with decreased DLCO after definitive radiotherapy than the GG/AG genotypes [univariate coefficient, −0.122; 95% confidence interval ( CI ), −0.236 to −0.008; P = 0.037; and multivariate coefficient, −0.102; 95% CI , −0.198 to −0.005; P = 0.038]. No such correlations were found for rs228590 (univariate coefficient, −0.096; 95% CI , −0.208 to 0.017; P = 0.096). Conclusions The AA genotype of ATM rs189037 was associated with higher risk of lung injury than were the GG/AG genotypes in patients with NSCLC treated with radiotherapy. This finding should be validated prospectively with other patient populations.