[Effects of oxidative DNA damage induced by polycyclic aromatic hydrocarbons and genetic polymorphism of the paraoxonase-1 (PON1) gene on lung cancer].
OBJECTIVE
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-OH-dG 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.
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
Kim
Yong-Dae
YD
Kang
Jong-Won
JW
Kim
Heon
H
D043303:Aryldialkylphosphatase / Q000235:genetics*; D016022:Case-Control Studies; D004249:DNA Damage / Q000187:drug effects*; D004781:Environmental Exposure; D006801:Humans; D007723:Korea; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology* / Q000506:poisoning; D011110:Polymorphism, Genetic / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires
D011084:Polycyclic Aromatic Hydrocarbons; D043303:Aryldialkylphosphatase