Copy Number Variants of GSTM1 and GSTT1 in Relation to Lung Cancer Risk in a Prospective Cohort Study

Copy Number Variants of GSTM1 and GSTT1 in Relation to Lung Cancer Risk in a Prospective Cohort Study
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DOI:
10.1016/j.annepidem.2009.03.003
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发表时间:
2009-08-01
影响因子:
5.6
通讯作者:
Alberg, Anthony J.
Alberg, Anthony J.
中科院分区:
医学3区
文献类型:
--
作者:
Lam, Tram Kim;Ruczinski, Ingo;Alberg, Anthony J.

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目的:以前的研究没有区分GSTM 1和GSTT 1的野生型和半合子基因型。在这项研究中,我们调查了野生型,半合子缺失,GSTM 1和GSTT 1纯合子缺失基因型和肺癌risk.METHODS:我们进行了巢式病例对照研究,143例原发性肺癌病例匹配447例无癌对照。使用基于实时聚合酶链反应(PCR)的检测进行基因分型。条件Logistic回归模型用于估计比值比(OR)和95%置信区间(CI)。与GSTM 1野生型携带者相比,肺癌的相对几率从1.49对于半合子和纯合子缺失基因型,分别为(95%CI = 0.66-3.40)至1.80(95%CI = 0.81-4.02)(p趋势= 0.13)。在那些每天吸烟少于一包并且GSTM 1缺失变异大于或等于一个的人中,(OR = 3.25; 95% CI = 0.93-11.34; p趋势= 0.07),而对于每天吸烟大于或等于一包的吸烟者,观察到相反的情况(OR = 0.80; 95%CI = 0.24-2.67; p-相互作用= 0.08)。GSTT 1 genotype.CONCLUSIONS:肺癌的风险增加的GSTM 1的缺失变异的数量增加,虽然协会是不显着的。区分野生型、半合子和纯合子缺失型GSTM 1基因型允许更精确地表征GSTM 1缺失变异体与肺癌之间的关联。Ann Epidemiol 2009;19:546-552. (C)2009 Elsevier Inc. All rights reserved.
PURPOSE: Previous studies did not discriminate wild-type from hemizygous genotypes of GSTM1 and GSTT1. In this study, we investigated wild-type, hemizygous deletion, and homozygous deletion genotypes of GSTM1 and GSTT1 and lung cancer risk.METHODS: We conducted a nested case-control study of 143 primary incident lung cancer cases matched to 447 cancer-free controls. Genotyping was carried out using a real-time polymerase chain reaction (PCR)-based assay. Conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI).RESULTS: Compared to GSTM1 wild-type carriers, the relative odds of lung cancer increased from 1.49 (95% CI = 0.66-3.40) to 1.80 (95% Cl = 0.81-4.02) for the hemizygous and homozygous deletion genotypes, respectively (p-trend = 0.13). The strongest associations were seen among those who smoked less than one pack per day and had greater than or equal to one deletion variant of GSTM1 (OR = 3.25; 95% CI = 0.93-11.34; p-trend = 0.07) whereas the reverse was observed for smokers who smoked greater than or equal to one pack per day (OR = 0.80; 95% CI = 0.24-2.67; p-interaction = 0.08). No clear associations were observed for GSTT1 genotypes.CONCLUSIONS: Risk of lung cancer increased as the number of deletion variants increased for GSTM1, although the associations were nonsignificant. Discriminating between the wild-type, hemizygous, and homozygous deletion GSTM1 genotypes permitted a more precise characterization of the associations between GSTM1 deletion variants and lung cancer. Ann Epidemiol 2009;19:546-552. (C) 2009 Elsevier Inc. All rights reserved.