J Prev Med Public Health.  2006 Mar;39(2):130-134.

Effects of Oxidative DNA Damage and Genetic Polymorphism of the Glutathion Peroxidase 1 (GPX1) and 8-Oxoguanine Glycosylase 1 (hOGG1) on Lung Cancer

• Lee CH
• Lee KY
• Choe KH
• Hong YC
• Noh SI
• Eom SY
• Ko YJ
• Zhang YW
• Yim DH
• Kang JW
• Kim H
• Kim YD

Abstract

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Keyword

Lung cancer; 8-Hydroxydeoxyguanosine; Glutathione peroxidase 1 (GPX1); 8-Oxoguanine glycosylase 1 (hOGG1); Genetic polymorphism

MeSH Terms

*DNA Damage
DNA Glycosylases/*genetics/urine
*Genetic Predisposition to Disease
Glutathione Peroxidase/*genetics/urine
Humans
Korea/epidemiology
Lung Neoplasms/etiology/*genetics
Oxidative Stress/*genetics
Questionnaires
Smoking/epidemiology