Wenzlaff A S, Cote M L, Bock C H, Land S J, Schwartz A G
Population Studies and Prevention Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
Carcinogenesis. 2005 Feb;26(2):395-401. doi: 10.1093/carcin/bgh326. Epub 2004 Nov 4.
Glutathione S-transferases detoxify polycyclic aromatic hydrocarbons found in tobacco smoke by glutathione conjugation. Polymorphisms within the GSTM1, GSTT1 and GSTP1 genes, coding for enzymes with deficient or reduced activity, have been studied as potential modifiers of lung cancer risk. It is hypothesized that risk associated with potential susceptibility gene polymorphisms might be most evident at low levels of exposure. Never smokers developing lung cancer represent a highly susceptible subset of the population, exposed to tobacco carcinogens only through environmental tobacco smoke. This population-based case-control study examines the association between GSTM1, GSTT1 and GSTP1 genotypes and lung cancer in one of the largest samples of never smokers to date. Cases (n = 166) were identified through the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and age- and race-matched population-based controls (n = 181) were identified using random digit dialing. Overall, there was no significant association between single or combinations of genotypes at GSTM1, GSTT1 or GSTP1 and lung cancer risk after adjustment for age, race, sex and household ETS exposure in years. However, in never smokers exposed to 20 or more years of household ETS, carrying the GSTM1 null genotype was associated with a 2.3-fold increase in risk [95% confidence interval (CI) 1.05-5.13]. Individuals in this high ETS exposure category carrying the GSTM1 null and the GSTP1 Val allele were at over 4-fold increased risk of developing lung cancer (OR = 4.56, 95% CI: 1.21-17.21). These findings suggest that in the presence of ETS, the GSTM1 genotype both alone and in combination with the GSTP1 genotype alters the risk of developing lung cancer among never smokers.
谷胱甘肽S-转移酶通过谷胱甘肽结合作用使烟草烟雾中的多环芳烃解毒。编码活性不足或降低的酶的GSTM1、GSTT1和GSTP1基因内的多态性已被研究作为肺癌风险的潜在修饰因子。据推测，与潜在易感基因多态性相关的风险在低暴露水平时可能最为明显。从不吸烟却患肺癌的人代表了人群中一个高度易感的亚组，他们仅通过环境烟草烟雾接触烟草致癌物。这项基于人群的病例对照研究在迄今为止最大的从不吸烟者样本之一中，检验了GSTM1、GSTT1和GSTP1基因型与肺癌之间的关联。病例（n = 166）通过底特律大都市监测、流行病学和最终结果（SEER）项目确定，年龄和种族匹配的基于人群的对照（n = 181）通过随机数字拨号确定。总体而言，在对年龄、种族、性别和家庭ETS暴露年限进行调整后，GSTM1、GSTT1或GSTP1的单基因型或组合与肺癌风险之间没有显著关联。然而，在暴露于20年或更长时间家庭ETS的从不吸烟者中，携带GSTM1无效基因型与风险增加2.3倍相关[95%置信区间（CI）1.05 - 5.13]。在这个高ETS暴露类别中，携带GSTM1无效基因型和GSTP1 Val等位基因的个体患肺癌的风险增加了4倍多（OR = 4.56，95% CI：1.21 - 17.21）。这些发现表明，在存在ETS的情况下，GSTM1基因型单独以及与GSTP1基因型组合都会改变从不吸烟者患肺癌的风险。
