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首页> 外文期刊>慢性疾病与转化医学：英文版 >Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for nonesmall-cell lung cancer
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Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for nonesmall-cell lung cancer

机译：非小细胞肺癌的ATM功能启动子rs189037变体与放疗后肺扩散能力的降低有关

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摘要

Objective: Single-nucleotide polymorphisms (SNPs) in the ataxia telangiectasiaemutated 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 nonesmall-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, ra-diation, 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.
机译：目的：共济失调性毛细血管扩张突变基因ATM中的单核苷酸多态性（SNPs）与肺癌放疗后的肺炎有关，但尚未评估其肺功能损害。在这里，我们研究了非小细胞肺癌（NSCLC）患者放疗后ATM中SNP与肺对一氧化碳（DLCO）扩散能力的变化之间的潜在关联。方法：从1998年11月至2009年6月，连续448例不能手术的原发性NSCLC患者接受了明确的（≥60 Gy）放疗，有或没有化疗。排除有胸外科，肿瘤扩张或肺癌史的患者后;没有可用于分析的DNA样品;或在放疗前12个月和放疗后12个月内未进行肺功能检查，确定了100例患者为研究对象。我们对先前发现与辐射诱发的肺炎相关的ATM的两个SNP（rs189037和rs228590）进行了基因分型，并通过逻辑回归分析评估了这些SNP与DLCO损伤（降低）之间的潜在相关性。结果：单因素和多因素分析显示，与GG / AG基因型相比，放疗后ATM rs189037的AA基因型与DLCO降低相关（单因素系数为-0.122; 95％置信区间（CI）为-0.236至-0.008; P = 0.037;多变量系数-0.102; 95％CI，-0.198至-0.005; P = 0.038）rs228590未发现此类相关性（单变量系数-0.096; 95％CI，-0.208至0.017; P = 0.096） ）。结论：ATM rs189037的AA基因型与放疗治疗的NSCLC患者的GG / AG基因型相比，具有更高的肺损伤风险。该发现应与其他患者人群进行前瞻性验证。

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  • 来源
    《慢性疾病与转化医学：英文版》 |2018年第1期|P.59-66|共8页
  • 作者

    Jose Luis Lopez Guerra; Yi-Peng Song; Quynh-Nhu Nguyen; Daniel R. Gomez; Zhongxing Liao; Ting Xu;

  • 作者单位

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville 41013, Spain;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville 41013, Spain;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville 41013, Spain;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville 41013, Spain;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville 41013, Spain;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Virgen del Rocío University Hospital, Seville 41013, Spain;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

    Department of Radiation Oncology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China;

    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;

  • 收录信息 中国科学引文数据库(CSCD);
  • 原文格式 PDF
  • 正文语种 CHI
  • 中图分类 肿瘤学;
  • 关键词

    Nonesmall-cell lung cancer; Radiation therapy; Ataxia telangiectasia-mutated gene; Single-nucleotide polymorphisms;

    机译：非小细胞肺癌;放射治疗;共济失调毛细血管扩张突变基因;单核苷酸多态性;
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