Effects of Oxidative DNA Damage Induced by Polycyclic Aromatic Hydrocarbons and Genetic Polymorphism of the Paraoxonase-1 (PON1) Gene on Lung Cancer

다환성 방향족 탄화수소 노출에 의한 DNA 산화적 손상과 Paraoxonase-1(PON1) 유전자 다형성이 폐암 발생에 미치는 영향

  • Lee, Chul-Ho (Department of Preventive Medicine, College of Medicine, Chungbuk National University) ;
  • Lee, Kye-Young (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Choe, Kang-Hyeon (Department of Internal Medicine, College of Medicine, Chungbuk National University) ;
  • Hong, Yun-Chul (Department of Preventive Medicine, Seoul National Univerxity College of Medicine, Department of Preventive Medicine, Seoul National University, Institute of Environmental Medicine, SNUMRC) ;
  • Kim, Yong-Dae (Department of Preventive Medicine, College of Medicine, Chungbuk National University) ;
  • Kang, Jong-Won (Department of Preventive Medicine, College of Medicine, Chungbuk National University, Department of Preventive Medicine, Seoul National University, Institute of Environmental Medicine, SNUMRC) ;
  • Kim, Heon (Department of Preventive Medicine, College of Medicine, Chungbuk National University, Department of Preventive Medicine, Seoul National University, Institute of Environmental Medicine, SNUMRC)
  • 이철호 (충북대학교 의과대학 예방의학교실) ;
  • 이계영 (단국대학교 의과대학 내과학교실) ;
  • 최강현 (충북대학교 의과대학 내과학교실) ;
  • 홍윤철 (서울대학교 의과대학 예방의학교실, 서울대학교 의학연구원 환경의학연구소) ;
  • 김용대 (충북대학교 의과대학 예방의학교실) ;
  • 강종원 (충북대학교 의과대학 예방의학교실, 서울대학교 의학연구원 환경의학연구소) ;
  • 김헌 (충북대학교 의과대학 예방의학교실, 서울대학교 의학연구원 환경의학연구소)
  • Published : 2005.09.01

Abstract

Objectives : 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.

Keywords

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