Saarikoski S T, Voho A, Reinikainen M, Anttila S, Karjalainen A, Malaveille C, Vainio H, Husgafvel-Pursiainen K, Hirvonen A
Finnish Institute of Occupational Health, Helsinki.
Int J Cancer. 1998 Aug 12;77(4):516-21. doi: 10.1002/(sici)1097-0215(19980812)77:4<516::aid-ijc7>3.0.co;2-x.
Glutathione S-transferases (GSTs) are known to take part in detoxification of many potentially carcinogenic compounds. Therefore, polymorphisms of the GST genes have been considered as potentially important modifiers of individual risk of environmentally induced cancers. The association between lack of glutathione S-transferase M1 gene (GSTM1 null genotype) and susceptibility to smoking-related lung cancer has been actively studied, with contradictory results. In contrast, little is known about the more recently found polymorphisms in GSTM3, GSTP1 and GSTT1 genes with respect to individual responses to environmental exposures. In this study, we determined the genotype distribution of all these genes, and their combinations, among 208 Finnish lung cancer patients and 294 population controls. None of the genotypes studied had a statistically significant effect on lung cancer risk, when studied separately. However, a significant association was observed for concurrent lack of the GSTM1 and GSTT1 genes and susceptibility to squamous cell carcinoma. For that cell type, the risk was more than 2-fold when compared with that of individuals having other genotype combinations (OR = 2.3; 95% CI = 1.0-5.3; p = 0.05). Moreover, the risk was mostly attributable to patients with smoking history of 40 pack-years or less (OR = 2.9; 95% CI = 1.1-7.7; p = 0.03). In contrast, this genotype combination did not affect the risk for other histological types of lung cancer, and the other genotype combinations had no effects on individual susceptibility to this malignancy. The overall role of GST polymorphisms in modifying the lung cancer risk may therefore be more limited than has been so far anticipated.
谷胱甘肽S-转移酶（GSTs）已知参与许多潜在致癌化合物的解毒过程。因此，GST基因的多态性被认为是个体环境诱导癌症风险的潜在重要调节因子。缺乏谷胱甘肽S-转移酶M1基因（GSTM1无效基因型）与吸烟相关肺癌易感性之间的关联已得到积极研究，但结果相互矛盾。相比之下，对于最近在GSTM3、GSTP1和GSTT1基因中发现的多态性在个体对环境暴露的反应方面了解甚少。在本研究中，我们确定了208例芬兰肺癌患者和294例人群对照中所有这些基因及其组合的基因型分布。单独研究时，所研究的基因型均对肺癌风险无统计学显著影响。然而，观察到GSTM1和GSTT1基因同时缺乏与鳞状细胞癌易感性之间存在显著关联。对于该细胞类型，与具有其他基因型组合的个体相比，风险增加了2倍多（OR = 2.3；95%CI = 1.0 - 5.3；p = 0.05）。此外，风险主要归因于吸烟史为40包年或更少的患者（OR = 2.9；95%CI = 1.1 - 7.7；p = 0.03）。相比之下，这种基因型组合不影响其他组织学类型肺癌的风险，且其他基因型组合对该恶性肿瘤的个体易感性也无影响。因此，GST多态性在改变肺癌风险方面的总体作用可能比迄今预期的更为有限。
