Sørensen Mette, Autrup Herman, Tjønneland Anne, Overvad Kim, Raaschou-Nielsen Ole
Institute of Cancer Epidemiology, The Danish Cancer Society, Copenhagen, Denmark.
Int J Cancer. 2004 Jun 10;110(2):219-24. doi: 10.1002/ijc.20075.
Glutathione S-transferases (GSTs) are involved in detoxification of carcinogens, e.g., from tobacco smoke. Therefore, polymorphisms in the GST genes have been considered as potential modifiers of individual cancer risk. In a population-based case-cohort study where cases and the subcohort sample were matched on duration of smoking, we investigated the occurrence of lung cancer and histological subtypes of lung cancer in relation to deletion polymorphism in both GSTM1 and GSTT1, single nucleotide polymorphisms (SNPs) in GSTP1 (Ile105Val and Ala114Val) and a 3 base pair deletion polymorphism in GSTM3. We further investigated the effects of the GST polymorphisms on lung cancer risk within subgroups of subjects defined by gender and age. The results showed a 2.4-fold (CI = 1.31-4.41) increased risk of lung cancer in GSTT1 null-genotype carriers but no significant effects of the polymorphisms in GSTM1, GSTM3, GSTP1-105 or GSTP1-114. The association was strongest in lower age groups, with a 9.6-fold increase in risk for subjects with the GSTT1 null-genotype in the 50-55 years age interval (CI = 3.03-30.59). Positive associations were found for GSTT1 within all major histological subtypes. Squamous cell carcinoma was the histological type most strongly associated with the GSTT1 genotype, with a 5.0-fold (CI = 2.26-11.18) increase in risk for subjects carrying the GSTT1 null-genotype. The effects of the GSTT1 null-genotype seemed stronger in the presence of the GSTM1 null-genotype or the GSTP1-105 variant allele. These results suggest that the GSTT1 null-genotype is associated with an increased risk of lung cancer, especially in younger individuals.
谷胱甘肽S-转移酶（GSTs）参与致癌物的解毒过程，例如来自烟草烟雾中的致癌物。因此，GST基因的多态性被认为是个体癌症风险的潜在调节因素。在一项基于人群的病例-队列研究中，病例组和亚队列样本根据吸烟时长进行匹配，我们调查了肺癌的发生情况以及肺癌的组织学亚型与GSTM1和GSTT1基因的缺失多态性、GSTP1基因的单核苷酸多态性（SNPs，Ile105Val和Ala114Val）以及GSTM3基因的3个碱基对缺失多态性之间的关系。我们还进一步研究了GST多态性在按性别和年龄定义的受试者亚组中对肺癌风险的影响。结果显示，GSTT1基因无效基因型携带者患肺癌的风险增加了2.4倍（置信区间=1.31-4.41），但GSTM1、GSTM3、GSTP1-105或GSTP1-114基因的多态性没有显著影响。这种关联在较低年龄组中最为强烈，在50-55岁年龄区间内，GSTT1基因无效基因型受试者的风险增加了9.6倍（置信区间=3.03-30.59）。在所有主要组织学亚型中均发现GSTT1基因呈正相关。鳞状细胞癌是与GSTT1基因型关联最强烈的组织学类型，GSTT1基因无效基因型携带者的风险增加了5.0倍（置信区间=2.26-11.18）。在存在GSTM1基因无效基因型或GSTP1-105变异等位基因的情况下，GSTT1基因无效基因型的影响似乎更强。这些结果表明，GSTT1基因无效基因型与肺癌风险增加有关，尤其是在较年轻个体中。
