Lee Chul-Ho, Lee Kye Young, Choe Kang-Hyeon, Hong Yun-Chul, Noh Sung-Il, Eom Sang-Yong, Ko Young-Jun, Zhang Yan Wei, Yim Dong-Hyuk, Kang Jong-Won, Kim Heon, Kim Yong-Dae
Department of Preventive Medicine, College of Medicine Chungbuk National University.
J Prev Med Public Health. 2006 Mar;39(2):130-4.
Oxidative DNA damage is a known risk factor of lung cancer. The glutathione peroxidase (GPX) antioxidant enzyme that reduces hydrogen peroxide and lipid peroxides plays a significant role in protecting cells from the oxidative stress induced by reactive oxygen species. The aim of this case-control study was to investigate effects of oxidative stress and genetic polymorphisms of the GPX1 genes and the interaction between them in the carcinogenesis of lung cancer.
Two hundreds patients with lung cancer and 200 age- and sex-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and their environmental exposure to PAHs. The genotypes of the GPX1 and 8-oxoguanine glycosylase 1 (hOGG1) genes were examined and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) were measured.
Cigarette smoking was a significant risk factor for lung cancer. The levels of urinary 8-OH-dG were higher in the patients (p < 0.001), whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. The GPX1 codon 198 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Pro/Leu or Leu/Leu genotype of GPX1 were at a higher risk for lung cancer (adjusted OR = 2.29). In addition, these individuals were shown to have high urinary 8-OH-dG concentrations compared to the individuals with the GPX1 Pro/Pro genotype. On the other hand, the polymorphism of the hOGG1 gene did not affect the lung cancer risk and the oxidative DNA damage.
These results lead to a conclusion that individuals with the GPX1 Pro/Leu or Leu/Leu genotype would be more susceptible to the lung cancer induced by oxidative stress than those individuals with the Pro/Pro genotype.
氧化性DNA损伤是肺癌已知的风险因素。谷胱甘肽过氧化物酶（GPX）抗氧化酶可还原过氧化氢和脂质过氧化物，在保护细胞免受活性氧诱导的氧化应激方面发挥重要作用。本病例对照研究的目的是调查氧化应激和GPX1基因的遗传多态性及其相互作用在肺癌致癌过程中的影响。
本研究纳入了200例肺癌患者和200例年龄及性别匹配的对照。要求每位受试者完成一份关于其吸烟习惯和环境中多环芳烃暴露情况的问卷。检测GPX1和8-氧鸟嘌呤糖基化酶1（hOGG1）基因的基因型，并测量尿中1-羟基芘（1-OHP）、2-萘酚和8-羟基脱氧鸟苷（8-OH-dG）的浓度。
吸烟是肺癌的一个重要风险因素。患者尿中8-OH-dG水平较高（p<0.001），而对照组尿中1-OHP和2-萘酚水平较高。GPX1密码子198多态性与肺癌风险增加有关。携带GPX1 Pro/Leu或Leu/Leu基因型的个体患肺癌的风险更高（调整后的OR=2.29）。此外，与具有GPX1 Pro/Pro基因型的个体相比，这些个体的尿中8-OH-dG浓度较高。另一方面，hOGG1基因的多态性不影响肺癌风险和氧化性DNA损伤。
这些结果得出结论，与具有Pro/Pro基因型的个体相比，具有GPX1 Pro/Leu或Leu/Leu基因型的个体更容易受到氧化应激诱导的肺癌影响。
