住宅氡气、DNA 损伤与修复相关的遗传多态性

Residential radon, genetic polymorphisms in DNA damage and repair-related.

机构信息

Service of Preventive Medicine, University Hospital Complex of Ourense, Spain; Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Spain.

Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Spain; CIBER de Epidemiología y Salud Pública CIBERESP, Spain; Department of Epidemiology, Brown School of Public Health, Brown University, Providence, Rhode Island, USA.

出版信息

Lung Cancer. 2019 Sep;135:10-15. doi: 10.1016/j.lungcan.2019.07.003. Epub 2019 Jul 4.

DOI:10.1016/j.lungcan.2019.07.003

PMID:31446980

Abstract

OBJECTIVES

To analyze the relationship of GSTT1, GSTM1, XRCC1 (rs25487), ERCC1 (rs11615, rs3212986), ERCC2 (rs13181), XRCC3 (rs861539), OGG1 (rs1052133), and Alpha-1-Antitrypsin mutations (AAT) with the risk of lung cancer in never-smokers, and ascertain if there is an effect modification between these polymorphisms and residential radon exposure.

MATERIAL AND METHODS

We designed a multicenter hospital-based case-control study in a radon-prone area. 322 cases and 338 controls, all never-smokers, were included. They were selected using a frequency sampling based on sex and age distribution of the cases. Participants donated 3 ml. of whole blood used to determine genotype for polymorphisms. They placed a radon detector to measure residential radon exposure in their dwelling.

RESULTS

The OR for deleted GSTM1 patients was 3.46 (95% CI = 1.52-7.89) at residential radon exposures above 200 Bq/m. The ERCC1 rs3212986 polymorphism was the most associated with the risk of developing lung cancer, both for low and high radon exposures. The ERCC1 rs321986 GT and TT genotypes (at radon concentrations >200 Bq/m) were more significantly associated with higher lung cancer risk (OR = 2.40, 95% CI = 1.29-4.45; OR = 4.45, 95% CI = 1.26-15.7, respectively).

CONCLUSIONS

These findings support the hypothesis that certain polymorphisms in genes involved in DNA-repair and carriers of GSTM1 deletion have an increased risk of lung cancer in never-smokers exposed to residential radon.

摘要

目的

分析 GSTT1、GSTM1、XRCC1（rs25487）、ERCC1（rs11615、rs3212986）、ERCC2（rs13181）、XRCC3（rs861539）、OGG1（rs1052133）和 Alpha-1-抗胰蛋白酶突变（AAT）与非吸烟者肺癌风险的关系，并确定这些多态性与住宅氡暴露之间是否存在效应修饰作用。

材料和方法

我们在一个氡高发地区设计了一项多中心医院病例对照研究。共纳入 322 例病例和 338 例对照，均为从不吸烟者。根据病例的性别和年龄分布，采用频率抽样法选择参与者。参与者捐献 3ml 全血，用于确定多态性的基因型。他们在住所放置一个氡探测器来测量住宅氡暴露。

结果

在住宅氡暴露高于 200 Bq/m 时，缺失 GSTM1 患者的 OR 为 3.46（95%CI=1.52-7.89）。ERCC1 rs3212986 多态性与低和高氡暴露均与肺癌风险最相关。ERCC1 rs321986 GT 和 TT 基因型（在氡浓度>200 Bq/m 时）与更高的肺癌风险更为显著相关（OR=2.40，95%CI=1.29-4.45；OR=4.45，95%CI=1.26-15.7）。