Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy St, 91-348, Lodz, Poland.
Genes Nutr. 2007 Dec;2(3):287-94. doi: 10.1007/s12263-007-0057-y. Epub 2007 Oct 16.
Oxidative stress and xenobiotic metabolizing enzymes are suspected to be related to carcinogenesis by different cellular mechanisms. Hence, our study aimed at identifying potential relationships between antioxidant defense parameters measured in blood and glutathione S-transferase (GST) genetic polymorphisms of four GST izoenzymes in lung cancer patients and reference individuals. The case-control study included 404 lung cancer patients and 410 non-cancer subjects as controls, matched by age, gender and place of living (central Poland). In control subjects with GSTM3A/A, GSTT1 null, GSTM1 null + GSTT1 null, GSTM3A/A + GSTT1 null genotype, glutathione peroxidase activity was significantly higher (P < 0.05) than in controls possessing respective potential protective GST genotypes. Controls with GSTM3A/A + GSTP1B genotype presented significantly higher ceruloplasmin activity (P < 0.05) than GSTM3B + GSTP1A/A carriers. Zinc level was significantly higher (P < 0.05) in controls and cases with GSTP1B + GSTT1 null genotype and in cases with GSTM1 null + GSTP1B genotype, when compared with respective potential protective GST genotypes. This case-control study indicates that particular defective GST genotypes may enhance the defense against oxidative stress. The potential relationship between the investigated antioxidative enzymes and microelements, and common functional genetic polymorphism of GST was observed mostly in control subjects.
氧化应激和外源代谢酶被怀疑通过不同的细胞机制与致癌作用有关。因此,我们的研究旨在确定肺癌患者和参考个体血液中抗氧化防御参数与谷胱甘肽 S-转移酶 (GST) 四种同工酶的遗传多态性之间的潜在关系。这项病例对照研究包括 404 名肺癌患者和 410 名非癌症对照,按年龄、性别和居住地点(波兰中部)匹配。在 GSTM3A/A、GSTT1 缺失、GSTM1 缺失+GSTT1 缺失、GSTM3A/A+GSTT1 缺失基因型的对照个体中,谷胱甘肽过氧化物酶活性显著升高(P<0.05)。与各自具有潜在保护 GST 基因型的对照个体相比。GSTM3A/A+GSTP1B 基因型的对照个体的铜蓝蛋白活性显著升高(P<0.05)。与各自具有潜在保护 GST 基因型的对照个体相比。与各自具有潜在保护 GST 基因型的对照个体相比。锌水平在 GSTP1B+GSTT1 缺失基因型的对照和病例以及 GSTM1 缺失+GSTP1*B 基因型的病例中显著升高(P<0.05)。这项病例对照研究表明,特定的缺陷 GST 基因型可能增强对氧化应激的防御。在所研究的抗氧化酶和微量元素与 GST 常见功能遗传多态性之间的潜在关系主要在对照个体中观察到。