Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer

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...

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Autores principales:	Jose Luis Lopez Guerra, Yi-Peng Song, Quynh-Nhu Nguyen, Daniel R. Gomez, Zhongxing Liao, Ting Xu
Formato:	article
Lenguaje:	EN
Publicado:	KeAi Communications Co., Ltd. 2018
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/75b573dda7ad4353bd2d96855d461129
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spelling	oai:doaj.org-article:75b573dda7ad4353bd2d96855d4611292021-12-02T10:50:18ZFunctional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer2095-882X10.1016/j.cdtm.2018.02.006https://doaj.org/article/75b573dda7ad4353bd2d96855d4611292018-03-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2095882X17300920https://doaj.org/toc/2095-882XObjective: 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. Keywords: Non–small-cell lung cancer, Radiation therapy, Ataxia telangiectasia-mutated gene, Single-nucleotide polymorphismsJose Luis Lopez GuerraYi-Peng SongQuynh-Nhu NguyenDaniel R. GomezZhongxing LiaoTing XuKeAi Communications Co., Ltd.articleMedicine (General)R5-920ENChronic Diseases and Translational Medicine, Vol 4, Iss 1, Pp 59-66 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Jose Luis Lopez Guerra Yi-Peng Song Quynh-Nhu Nguyen Daniel R. Gomez Zhongxing Liao Ting Xu Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer
description	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. Keywords: Non–small-cell lung cancer, Radiation therapy, Ataxia telangiectasia-mutated gene, Single-nucleotide polymorphisms
format	article
author	Jose Luis Lopez Guerra Yi-Peng Song Quynh-Nhu Nguyen Daniel R. Gomez Zhongxing Liao Ting Xu
author_facet	Jose Luis Lopez Guerra Yi-Peng Song Quynh-Nhu Nguyen Daniel R. Gomez Zhongxing Liao Ting Xu
author_sort	Jose Luis Lopez Guerra
title	Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer
title_short	Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer
title_full	Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer
title_fullStr	Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer
title_full_unstemmed	Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer
title_sort	functional promoter rs189037 variant of atm is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer
publisher	KeAi Communications Co., Ltd.
publishDate	2018
url	https://doaj.org/article/75b573dda7ad4353bd2d96855d461129
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Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non–small-cell lung cancer

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