Journal of Preventive Medicine and Public Health

The Korean Society for Preventive Medicine (대한예방의학회)
권호 표지

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

GPX1 및 hOGG1 유전자다형성에 따른 유전자의 산화적 손상 및 폐암 발생 위험도 평가

  • 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 (Internal Medicine, College of Medicine Chungbuk National University) ;
  • Hong, Yun-Chul (Department of Preventive Medicine, Seoul National University College of Medicine, Institute of Environmental Medicine, SNUMRC) ;
  • Noh, Sung-Il (Department of Preventive Medicine, College of Medicine Chungbuk National University) ;
  • Eom, Sang-Yong (Department of Preventive Medicine, College of Medicine Chungbuk National University) ;
  • Ko, Young-Jun (Department of Preventive Medicine, College of Medicine Chungbuk National University) ;
  • Zhang, Yan-Wei (Department of Preventive Medicine, College of Medicine Chungbuk National University) ;
  • Yim, Dong-Hyuk (Department of Preventive Medicine, College of Medicine Chungbuk National University) ;
  • Kang, Jong-Won (Department of Preventive Medicine, College of Medicine Chungbuk National University, Institute of Environmental Medicine, SNUMRC) ;
  • Kim, Heon (Department of Preventive Medicine, College of Medicine Chungbuk National University, Institute of Environmental Medicine, SNUMRC) ;
  • Kim, Yong-Dae (Department of Preventive Medicine, College of Medicine Chungbuk National University)
  • 이철호 (충북대학교 의과대학 예방의학교실) ;
  • 이계영 (단국대학교 의과대학 내과학교실) ;
  • 최강현 (충북대학교 의과대학 내과학교실) ;
  • 홍윤철 (서울대학교 의과대학 예방의학교실, 서울대학교 의학연구원 환경의학연구소) ;
  • 노성일 (충북대학교 의과대학 예방의학교실) ;
  • 엄상용 (충북대학교 의과대학 예방의학교실) ;
  • 고영준 (충북대학교 의과대학 예방의학교실) ;
  • 장연위 (충북대학교 의과대학 예방의학교실) ;
  • 임동혁 (충북대학교 의과대학 예방의학교실) ;
  • 강종원 (충북대학교 의과대학 예방의학교실, 서울대학교 의학연구원 환경의학연구소) ;
  • 김헌 (충북대학교 의과대학 예방의학교실, 서울대학교 의학연구원 환경의학연구소) ;
  • 김용대 (충북대학교 의과대학 예방의학교실)
  • Published : 2006.03.01
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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 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.

Keywords

References

  1. Central Cancer Registry Center in Korea. Annual Report of the Central Cancer Registry in Korea. Seoul: Ministry of Health and Welfare; 2003
  2. Hennninki K. Environmental carcinogens. In: Cooper CS, Grover RL (eds) Chemical Carcinogenesis and Mutagenesis. vol I. New York: Raven Press; 1990. p. 33-62
  3. International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Human. Polynuclear Aromatic Compounds, part 1, vol 32. Lyon: IARC; 1983
  4. Flowers L, Ohnishi ST, Penning TM. DNA strand scission by polycyclic aromatic hydrocarbon o-quinones: Role of reactive oxygen species, Cu(II)/Cu(I) redox cycling, and o-semiquinone anion radicals. Biochemistry 1997;36:8640-8648 https://doi.org/10.1021/bi970367p
  5. Ohnishi S. Kawanishi S. Double base lesions of DNA by a metabolites of carcinogenic benzo[a]pyrene. Biochem Biophys Res Commun 2002;290:778-782 https://doi.org/10.1006/bbrc.2001.6249
  6. Floyd RA, Watson JJ, Harris J, West M, Wong PK. Formation of 8-hydroxydeoxyguanosine, hydroxyl free radical adduct of DNA in granulocytes exposed to the tumor promoter, tetradecanoylphorbolacetate. Biochem Biophys Res Commun 1986; 137: 841-846 https://doi.org/10.1016/0006-291X(86)91156-3
  7. Floyd RA. The role of 8-hydroxyguanine in carcinogenesis. Carcinogenesis 1990; 11: 1447-1450 https://doi.org/10.1093/carcin/11.9.1447
  8. Lee CH, Lee KY, Choe KH, Hong YC, Kim YD, Kang JW, Kim H. Effects of oxidative DNA damage induced by polycyclic aromatic hydrocarbons and genetic polymorphism of the paraoxonase-l (PON1) gene on lung cancer. J Prev Med Pub Health 2005; 38(3): 345-350 (Korean)
  9. Kim YD, Lee CH, Nan HM, Kang JW, Kim H. Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary I-hydroxypyrene and 2-naphthol concentrations. J Occup Health 2003; 45: 160-167 https://doi.org/10.1539/joh.45.160
  10. Chuang CY, Lee CC, Chang YK, Sung FC. Oxidative DNA damage estimated by urinary 8-hydroxydeoxyguanosine: influence of taxi driving, smoking and areca chewing. Chemosphere 2003; 52: 1163-1171 https://doi.org/10.1016/S0045-6535(03)00307-2
  11. Chu FF, Esworthy RS, Chu PG, Longmate JA, Huycke MM, Wilczynski S, Doroshow JH. Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Cancer Res 2004; 64: 962-968 https://doi.org/10.1158/0008-5472.CAN-03-2272
  12. Esworthy RS, Mann JR, Sam M, Chu FF. Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunum crypts from gamma-irradiation damage. Am J Physiol Gastroimest Liver Physiol 2000; 279: G426-436 https://doi.org/10.1152/ajpgi.2000.279.2.G426
  13. Ratnasinghe D, Tangrea JA, Andersen MR, Barrett MJ, Virtamo J, Taylor PR, Albanes D. Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Res 2000; 60: 6381-6383
  14. Shinmura K, Kasai H, Sasaki A, Sugimura H, Yokota J. 8-hydroxyguanine (7,8-dihydro-8oxoguanine) DNA glycosylase and AP lyase activities of hOGG1 protein and their substrate specificity. Mutat Res 1997; 385: 75-82 https://doi.org/10.1016/S0921-8777(97)00041-4
  15. Girard PM, D'Ham C, Cadet J, Boiteux S. Opposite base-dependent excision of 7,8dihydro-8-oxoadenine by the Ogg1 protein of Saccharomyces cerevisiae. Carcinogenesis 1998;19: 1299-1305 https://doi.org/10.1093/carcin/19.7.1299
  16. American Cancer Society. Tobacco Use. In: American Cancer Society, (Ed). Cancer Facts & Figures 2001. Atlanta: American Cancer Society; 2001. p. 29-32
  17. Sunaga N, Kohno T, Yanagitani N, Sugimura H, Kunitoh H, Tamura T, Takei Y, Tsuchiya S, Saito R, Yokota J. Contribution of the NQO1 and GSTT1 polymorphisms to lung adenocarcinoma susceptibility. Cancer Epidemiol Biomarkers Prev 2002; 11: 730-738
  18. Kim JI, Park YJ, Kim KH, Kim JI, Song BJ, Lee MS, Kim CN, Chang SH. hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer. World J Gastroenterol 2003; 9: 956-960 https://doi.org/10.3748/wjg.v9.i5.956