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. 2005 Aug 19;95(12):977–983. doi: 10.1111/j.1349-7006.2004.tb03186.x

hOGGl Ser326Cys polymorphism, interaction with environmental exposures, and gastric cancer risk in Japanese populations

Hiromasa Tsukino 1, Tomoyuki Hanaoka 1,, Tetsuya Otani 1, Motoki Iwasaki 1, Minatsu Kobayashi 1,2, Megumi Hara 3, Syusuke Natsukawa 4, Kozo Shaura 5, Yoichi Koizumi 6, Yoshio Kasuga 7, Shoichiro Tsugane 1
PMCID: PMC11158253  PMID: 15596047

Abstract

Oxidative DNA damage caused by reactive oxygen species (ROS) generated by Helicobacter pylori (H. pylori) infection or smoking may be a cause of gastric cancer development. 8‐Hydroxydeoxyguanine (8‐OHdG) formation is one of the most common types of oxidative DNA damage, while human oxoguanine glycosylase 1 (hOGGl) is responsible for repairing 8‐OHdG lesions. Among several hOGGl gene polymorphisms, the SerCys polymorphism at position 326 is related to biological function. To investigate the association between Ser326Cys hOGGl polymorphism and gastric cancer in relation to the potential risk factors of gastric cancer and antioxidant dietary or nutrient intakes, we conducted a case‐control study with 142 histologically‐confirmed gastric cancer cases and 271 age, sex‐matched healthy controls in Japanese populations. Overall, neither the hOGG1 Ser/Cys nor the Cys/Cys genotype was associated with risk of gastric cancer, compared with the Ser/Ser genotype. A significant interaction was observed between hOGGl Ser/Cys or Cys/Cys genotype and atrophic gastritis (P for interaction =0.03). No significant interaction was found between hOGGl genotype and antioxidant dietary or nutrient intakes. The results of the present study suggest that patients with atrophic gastritis in conjunction with the hOGGl Cys allele might have a higher susceptibility to gastric cancer.


AAbbreviations:

8‐OHdG

8‐hydroxydeoxyguanine

95% Cl

95% confidence interval

FFQ

food‐frequency questionnaire

hOGGl

human oxoguanine glycosylase 1

H. pylori

Helicobacter pylori

JA

Japan Agricultural Cooperative

OR

odds ratio

ROS

reactive oxygen species

References

  • 1. Kaneko S, Yoshimi I. Mortality trend of stomach cancer in Japan: 1960–2000. Jpn J Clin Oncol 2003; 33: 105–6. [PubMed] [Google Scholar]
  • 2. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process‐First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 1992; 52: 6735–40. [PubMed] [Google Scholar]
  • 3. Nomura A, Grove JS, Stemmermann GN, Severson RK. A prospective study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption. Cancer Res 1990; 50: 627–31. [PubMed] [Google Scholar]
  • 4. Correa P, Malcom G, Schmidt B, Fontham E, Ruiz B, Bravo JC, Bravo LE, Zarama G, Realpe JL. Review article: antioxidant micronutrients and gastric cancer. Aliment Pharmacol Ther 1998; 12 Suppl 1: 73–82. [DOI] [PubMed] [Google Scholar]
  • 5. Loft S, Deng XS, Tuo J, Wellejus A, Sorensen M, Poulsen HE. Experimental study of oxidative DNA damage. Free Radic Res 1998; 29: 525–39. [DOI] [PubMed] [Google Scholar]
  • 6. Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis 2000; 21: 361–70. [DOI] [PubMed] [Google Scholar]
  • 7. Kobayashi M, Tsubono Y, Sasazuki S, Sasaki S, Tsugane S. Vegetables, fruit and risk of gastric cancer in Japan: a 10‐year follow‐up of the JPHC Study Cohort I. Int J Cancer 2002; 102: 39–44. [DOI] [PubMed] [Google Scholar]
  • 8. Obst B, Wagner S, Sewing KF, Beil W. Helcobacter pylori causes DNA damage in gastric epithelial cells. Carcinogenesis 2000; 21: 1111–5. [PubMed] [Google Scholar]
  • 9. Bagchi D, McGinn TR, Ye X, Bagchi M, Krohn RL, Chatterjee A, Stohs SJ. Helicobacter Pylori‐induced oxidative stress and DNA damage in a primary culture of human gastric mucosal cells. Dig Dis Sci 2002; 47: 1405–12. [DOI] [PubMed] [Google Scholar]
  • 10. Church DF, Pryor WA. Free‐radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 1985; 64: 111–26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Ames BN. Endogenous oxidative DNA damage, aging, and cancer. Free Radic Res Commun 1989; 7: 121–8. [DOI] [PubMed] [Google Scholar]
  • 12. Shibutani S, Takeshita M, Grollman AP. Insertion of specific bases during DNA synthesis past the oxidation‐damaged base 8‐oxodG. Nature 1991; 349: 431–4. [DOI] [PubMed] [Google Scholar]
  • 13. Kasai H. Analysis of a form of oxidative DNA damage, 8‐hydroxy‐2′‐deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res 1997; 387: 147–63. [DOI] [PubMed] [Google Scholar]
  • 14. Greim H, Csanady G, Filser JG, Kreuzer P, Schwarz L, Wolff T, Werner S. Biomarkers as tools in human health risk assessment. Clin Chem 1995; 41: 1804–8. [PubMed] [Google Scholar]
  • 15. Nishioka K, Ohtsubo T, Oda H, Fujiwara T, Kang D, Sugimachi K, Nakabeppu Y. Expression and differential intracellular localization of two major forms of human 8‐oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs. Mol Biol Cell 1999; 10: 1637–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Elahi A, Zheng Z, Park J, Eyring K, McCaffrey T, Lazarus P. The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk. Carcinogenesis 2002; 23: 1229–34. [DOI] [PubMed] [Google Scholar]
  • 17. Xu J, Zheng SL, Turner A, Isaacs SD, Wiley KE, Hawkins GA, Chang BL, Bleecker ER, Walsh PC, Meyers DA, Isaacs WB. Associations between hOGGl sequence variants and prostate cancer susceptibility. Cancer Res 2002; 62: 2253–7. [PubMed] [Google Scholar]
  • 18. Kohno T, Shinmura K, Tosaka M, Tani M, Kim SR, Sugimura H, Nohmi T, Kasai H, Yokota J. Genetic polymorphisms and alternative splicing of the hOGGl gene, that is involved in the repair of 8‐hydroxyguanine in damaged DNA. Oncogene 1998; 16: 3219–25. [DOI] [PubMed] [Google Scholar]
  • 19. Le Marchand L, Donlon T, Lum‐Jones A, Seifried A, Wilkens LR. Association of the hOGGl Ser326Cys polymorphism with lung cancer risk. Cancer Epidemiol Biomarkers Prev 2002; 11: 409–12. [PubMed] [Google Scholar]
  • 20. Sugimura H, Kohno T, Wakai K, Nagura K, Genka K, Igarashi H, Morris BJ, Baba S, Ohno Y, Gao C, Li Z, Wang J, Takezaki T, Tajima K, Varga T, Sawaguchi T, Lum JK, Martinson JJ, Tsugane S, Iwamasa T, Shinmura K, Yokota J. hOGGl Ser326Cys polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1999; 8: 669–74. [PubMed] [Google Scholar]
  • 21. Xing DY, Tan W, Song N, Lin DX. Ser326Cys polymorphism in hOGGl gene and risk of esophageal cancer in a Chinese population. Int J Cancer 2001; 95: 140–3. [DOI] [PubMed] [Google Scholar]
  • 22. Chen L, Elahi A, Pow‐Sang J, Lazarus P, Park J. Association between polymorphism of human oxoguanine glycosylase 1 and risk of prostate cancer. J Urol 2003; 170: 2471–4. [DOI] [PubMed] [Google Scholar]
  • 23. Shinmura K, Kohno T, Kasai H, Koda K, Sugimura H, Yokota J. Infrequent mutations of the hOGGl gene, that is involved in the excision of 8‐hydroxyguanine in damaged DNA, in human gastric cancer. Jpn J Cancer Res 1998; 89: 825–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Takezaki T, Gao CM, Wu JZ, Li ZY, Wang JD, Ding JH, Liu YT, Hu X, Xu TL, Tajima K, Sugimura H. hOGGl Ser(326)Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese. Int J Cancer 2002; 99: 624–7. [DOI] [PubMed] [Google Scholar]
  • 25. Hanaoka T, Sugimura H, Nagura K, Ihara M, Li XJ, Hamada GS, Nishimoto I, Kowalski LP, Yokota J, Tsugane S. hOGGl exon7 polymorphism and gastric cancer in case‐control studies of Japanese Brazilians and non‐Japanese Brazilians. Cancer Lett 2001; 170: 53–61. [DOI] [PubMed] [Google Scholar]
  • 26. Kara M, Hanaoka T, Kobayashi M, Otani T, Adachi HY, Montani A, Natsukawa S, Shaura K, Koizumi Y, Kasuga Y, Matsuzawa T, Ikekawa T, Sasaki S, Tsugane S. Cruciferous vegetables, mushrooms, and gastrointestinal cancer risks in a multicenter, hospital‐based case‐control study in Japan. Nutr Cancer 2003; 46: 138–47. [DOI] [PubMed] [Google Scholar]
  • 27. Japanese Research Society for Gastric Cancer Study. The general rules for the gastric cancer study. 12th ed. Tokyo : Kanehara & Co Ltd; 1993. (in Japanese). [Google Scholar]
  • 28. Science and Technology Agency. Standard tables of food composition in Japan. The fourth revised edition. Tokyo : Printing Bureau, Ministry of Finance; 1982. (in Japanese). [Google Scholar]
  • 29. Sasaki S, Kobayashi M, Ishihara J, Tsugane S. Self‐administered food frequency questionnaire used in the 5‐year follow‐up survey of the JPHC Study: questionnaire structure, computation algorithms, and area‐based mean intake . J Epidemiol 2003; 13 Suppl: 13–22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Tsugane S, Sasaki S, Kobayashi M, Tsubono Y, Akabane M. Validity and reproducibility of the self‐administered food frequency questionnaire in the JPHC Study Cohort I: study design, conduct and participant profiles. J Epidemiol 2003; 13 Suppl: 2–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Ishihara J, Sobue T, Yamamoto S, Yoshimi I, Sasaki S, Kobayashi M, Takahashi T, Iitoi Y, Akabane M, Tsugane S. Validity and reproducibility of a self‐administered food frequency questionnaire in the JPHC Study Cohort II: study design, participant profile and results in comparison with Cohort I. J Epidemiol 2003; 13 Suppl: 134–47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Kabuto M, Imai H, Tsugane S, Watanabe S. Correlation between atrophic gastritis prevalence and gastric cancer mortality among middle‐aged men in 5 areas in Japan. J Epidemiol 1993; 3 Suppl: 35–9. [Google Scholar]
  • 33. Tsugane S, Kabuto M, Imai H, Gey F, Tei Y, Hanaoka T, Sugano K, Watanabe S. Helicobacter pylori, dietary factors, and atrophic gastritis in five Japanese populations with different gastric cancer mortality. Cancer Causes Control 1993; 4: 297–305. [DOI] [PubMed] [Google Scholar]
  • 34. Namekata T, Miki K, Kimmey M, Fritsche T, Hughes D, Moore D, Suzuki K. Chronic atrophic gastritis and Helicobacter pylori infection among Japanese Americans in Seattle. Am. J Epidemiol 2000; 151: 820–30. [DOI] [PubMed] [Google Scholar]
  • 35. Machida‐Montani A, Sasazuki S, Inoue M, Natsukawa S, Shaura K, Koizumi Y, Kasuga Y, Hanaoka T, Tsugane S. Association of Helicobacter pylori infection and environmental factors in non‐cardia gastric cancer in Japan. Gastric Cancer 2004; 7: 46–53. [DOI] [PubMed] [Google Scholar]
  • 36. Greenland S. Tests of fit. In: Rothman KJ, Greenland S, editors Modern epidemiology. 2nd ed. Philadelphia , PA : Lippincott Williams & Wilkins; 1998. p. 409–10. [Google Scholar]
  • 37. Ito H, Hamajima N, Takezaki T, Matsuo K, Tajima K, Hatooka S, Mitsudomi T, Suyama M, Sato S, Ueda R. A limited association of OGG1 Ser326Cys polymorphism for adenocarcinoma of the lung. J Epidemiol 2002; 12: 258–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Correa P. A human model of gastric carcinogenesis. Cancer Res 1988; 48: 3554–60. [PubMed] [Google Scholar]
  • 39. Lee BM, Jang JJ, Kim HS. Benzo[a]pyrene diol‐epoxide‐I‐DNA and oxidative DNA adducts associated with gastric adenocarcinoma. Cancer Lett 1998; 125: 61–8. [DOI] [PubMed] [Google Scholar]
  • 40. Lampe JW, Peterson S. Brassica, biotransformation and cancer risk: genetic polymorphisms alter the preventive effects of cruciferous vegetables. J Nutr 2002; 132: 2991–4. [DOI] [PubMed] [Google Scholar]
  • 41. Tsugane S, Tsuda M, Gey F, Watanabe S. Cross‐sectional study with multiple measurements of biological markers for assessing stomach cancer risks at the population level. Environ Health Perspect 1992; 98: 207–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Tsugane S, Sasazuki S, Kobayashi M, Sasaki S. Salt and salted food intake and subsequent risk of gastric cancer among middle‐aged Japanese men and women. Br J Cancer 2004; 90: 128–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Ekstrom AM, Held M, Hansson LE, Engstrand L, Nyren O. Helicobacter pylori in gastric cancer established by CagA immunoblot as a marker of past infection. Gastroenterology 2001; 121: 784–91. [DOI] [PubMed] [Google Scholar]

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