[Effects of oxidative DNA damage and genetic polymorphism of the glutathione peroxidase 1 (GPX1) and 8-oxoguanine glycosylase 1 (hOGG1) on lung cancer].
OBJECTIVE
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.
Lee
Chul-Ho
CH
Department of Preventive Medicine, College of Medicine Chungbuk National University.
Lee
Kye Young
KY
Choe
Kang-Hyeon
KH
Hong
Yun-Chul
YC
Noh
Sung-Il
SI
Eom
Sang-Yong
SY
Ko
Young-Jun
YJ
Zhang
Yan Wei
YW
Yim
Dong-Hyuk
DH
Kang
Jong-Won
JW
Kim
Heon
H
Kim
Yong-Dae
YD
D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics* / Q000652:urine; D020022:Genetic Predisposition to Disease; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000652:urine; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology; D011795:Surveys and Questionnaires; D000094765:Glutathione Peroxidase GPX1
D005979:Glutathione Peroxidase; D045647:DNA Glycosylases; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human