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English Abstract
- Effects of Oxidative DNA Damage Induced by Polycyclic Aromatic Hydrocarbons and Genetic Polymorphism of the Paraoxonase-1 (PON1) Gene on Lung Cancer.
- Chul Ho Lee, Kye Young Lee, Kang Hyeon Choe, Yun Chul Hong, Yong Dae Kim, Jong Won Kang, Heon Kim
- J Prev Med Public Health. 2005;38(3):345-350.
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Abstract
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Polycyclic aromatic hydrocarbons (PAHs), which are risk factors for lung cancer, have been reported to induce oxidative DNA damage. The paraoxonase (PON) plays a significant role in the detoxification of a variety of organophosphorous compounds, with paraoxonase-1 (PON1) being one of the endogenous free-radical scavenging systems in the human body. The aim of this case-control study was to investigate the effects of PAH exposure, oxidative stress and the Q192R polymorphism of PON1 genes, and their interactions in the carcinogenesis of lung cancer. METHODS: One hundred and seventy seven lung cancer patients and 177 age- and sex-matched controls were enrolled in this study. Each subject was asked to complete a questionnaire concerning their smoking habits and environmental exposure to PAHs. The Q192R genotypes of the PON1 gene was examined, and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8- hydroxydeoxyguanosine (8-OH-dG) measured. RESULTS: Cigarette smoking was found to be a significant risk factor for lung cancer. The urinary 8-OH-dG level was higher in the patients, whereas the urinary 1-OHP and 2- naphthol levels were higher in the controls. There was a significant correlation between the urinary levels of 8-OHdG and 1-OHP in both the cases and controls. The PON1 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Q/Q genotype of the PON1 gene were found to be at higher risk of developing lung cancer. There was a significant correlation between the urinary levels of 8-OH-dG and 1-OHP in those with the PON1 Q/Q genotype. CONCLUSIONS: These results lead to the conclusion that PAHs would induce oxidative DNA damage, especially in individuals with the PON1 Q/Q genotype. Therefore, people with the PON1 Q/Q genotype would be more susceptible to lung cancer than those with the R/R or Q/R genotypes of the PON1 gene. -
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