Genetic Polymorphism of Glutathione S-transferases M1 and T1, Tobacco Habits and Risk of Stomach Cancer in Mizoram, India

  • Malakar, Mridul (Regional Medical Research Centre, NE Region (Indian Council of Medical Research)) ;
  • Devi, K. Rekha (Regional Medical Research Centre, NE Region (Indian Council of Medical Research)) ;
  • Phukan, Rup Kumar (Regional Medical Research Centre, NE Region (Indian Council of Medical Research)) ;
  • Kaur, Tanvir (Indian Council of Medical Research) ;
  • Deka, Manab (Department of Biotechnology, Gauhati University) ;
  • Puia, Lalhriat (Directorate of Hospital and Medical Education) ;
  • Barua, Debajit (Directorate of Hospital and Medical Education) ;
  • Mahanta, Jagadish (Regional Medical Research Centre, NE Region (Indian Council of Medical Research)) ;
  • Narain, Kanwar (Regional Medical Research Centre, NE Region (Indian Council of Medical Research))
  • Published : 2012.09.30


Aim: The incidence of stomach cancer in Mizoram is highest in India. We have conducted a population based matched case-control study to identify environmental and genetic risk factors in this geographical area. Methods: A total of 102 histologically confirmed stomach cancer cases and 204 matched healthy population controls were recruited. GSTM1 and GSTT1 genotypes were determined by PCR and H. pylori infections were determined by ELISA. Results: Tobacco-smoking was found to be an important risk factor for high incidence of stomach cancer in Mizoram. Meiziol (local cigarette) smoking was a more important risk factor than other tobacco related habits. Cigarette, tuibur (tobacco smoke infused water) and betel nut consumption synergistically increased the risk of stomach cancer. Polymorphisms of GSTM1 and GSTT1 genes were not found to be directly associated with stomach cancer in Mizoram. However, they appeared to be effect modifiers. Persons habituated with tobacco smoking and/or tuibur habit had increased risk of stomach cancer if they carried the GSTM1 null genotype and GSTT1 non-null genotype. Conclusion: Tobacco smoking, especially meiziol is the important risk factor for stomach cancer in Mizoram. GSTM1 and GSTT1 genes modify the effect of tobacco habits. This study is a first step in understanding the epidemiology of stomach cancer in Mizoram, India.


  1. Anantharaman D, Chaubal PM, Kannan S, et al (2007). Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator. Carcinogenesis, 28, 1455-62.
  2. Bell DA, Taylor JA, Paulson DF, et al (1993). Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene Glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst, 85, 1159-64.
  3. Boeing H, Frentzel-Beyme R, Berger M, et al (1991). Casecontrol study on stomach cancer in Germany. Int J Cancer, 47, 858-64.
  4. Breslow NE, Day NE (1980). The analysis of case-control studies. Statistical methods in cancer research. IARC Scientific Publication No.5. Lyon (France). IARC p.1.
  5. Cai L, Yu SZ, Zhang ZF (2001). Glutathione S-transferases M1, T1 genotypes and the risk of gastric cancer: a case-control study. World J Gastroenterol, 7, 506-9.
  6. Chenevix-Trench G, Young J, Coggan M, et al (1995). Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset. Carcinogenesis, 16, 1655-7.
  7. Correa P (1992). Human gastric carcinogenesis: a multistep and multifactorial process-first American cancer society award lecture on cancer epidemiology and prevention. Cancer Res, 52, 6735-40.
  8. Eslick GD, Lim LL, Byles JE, et al (1999). Association of Helicobacter pylori infection with gastric carcinoma: a meta-analysis. Am J Gastroenterol, 94, 2373-9.
  9. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917.
  10. Gajalakshmi CK, Shanta V (1996). Lifestyle and risk of stomach cancer: a hospital-based case-control study. Int J Epidemiol, 25, 1146-53.
  11. Garcia-G MA, Quintero E, Bujanda L, et al (2012). Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer susceptibility and phenotype. Mutagenesis, 27, 771-7.
  12. Hansson LE, Baron J, Nyren O, et al (1994). Tobacco, alcohol and the risk of gastric cancer. A population-based casecontrol study in Sweden. Int J Cancer, 57, 26-31.
  13. IARC (2002). Monographs on the evaluation of carcinogenic risks to humans. Vol. 83. Lyon (France). IARC 83.
  14. Jedrychowski W, Boeing H, Wahrendorf J, et al (1993). Vodka consumption, tobacco smoking and risk of gastric cancer in Poland. Int J Epidemiol, 22, 606-13.
  15. Jing C, Huang ZJ, Duan YQ, et al (2012). Glulathione-Stransferases gene polymorphism in prediction of gastric cancer risk by smoking and Helicobacter pylori infection status. Asian Pac J Cancer Prev, 13, 3325-8.
  16. Kate V, Ananthakrishnan N (2000). Helicobacter pylori and gastric carcinoma: evidence for the link. Natl Med J India, 13, 329.
  17. Katoh T, Nagata N, Kuroda Y, et al (1996). Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. Carcinogenesis, 17, 1855-9.
  18. Khanna AK, Seth P, Nath G, et al (2002). Correlation of Helicobacter pylori and gastric carcinoma. J Postgrad Med, 48, 27-8.
  19. Mahanta J, Chetia M, Hazarika NC, et al (1998). Toxicity of tuibur, a unique form of tobacco smoke extract used in Mizoram, India. Curr Sci, 75, 381-4.
  20. Miwa H, Go MF, Sato N (2002). H. pylori and gastric cancer: the Asian enigma. Am J Gastroenterol, 97, 1106-12.
  21. National Cancer Registry Programme (NCRP) (2010). Threeyear report of the population based cancer registries 2006- 2008. (First report of 20 PBCRs in India), Bangalore. Indian Council Med Res, 11, 71-8.
  22. Parkin DM, Muir CS, Whelan SL, et al (2002). Cancer incidence in five continents. IARC Sci Pub, 7, 1555.
  23. Pemble S, Schroeder KR, Spencer SR, et al (1994). Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J, 300, 271-6.
  24. Phukan RK, Narain K, Zomawia E, et al (2006). Dietary habits and stomach cancer in Mizoram, India. J Gastroenterol, 41, 418-24.
  25. Phukan RK, Zomawia E, Hazarika NC, et al (2004). High prevalence of stomach cancer among the people of Mizoram, India. Curr Sci, 87, 285-6.
  26. Phukan RK, Zomawia E, Narain K, et al (2005). Tobacco use and stomach cancer in Mizoram, India. Cancer Epidemiol Biomarkers Prev, 14, 1892-6.
  27. Rao DN, Ganesh B (1998). Estimate of cancer incidence in India in 1991. Indian J Cancer, 35, 10-8.
  28. Rao DN, Ganesh B, Dinshaw KA, et al (2002). A case-control study of stomach cancer in Mumbai, India. Int J Cancer, 99, 727-31.
  29. Russo A, Maconi G, Spinelli P, et al (2001). Effect of lifestyle, smoking, and diet on development of intestinal metaplasia in H. pylori-positive subjects. Am J Gastroenterol, 96, 1402-8.
  30. Saadat I, Saadat M (2001). Glutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers. Cancer Lett, 169, 21-6.
  31. Setiawan VW, Zhang ZF, Yu GP, et al (2000). GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population. Cancer Epidemiol Biomarkers Prev, 9, 73-80.
  32. Singh K, Ghoshal UC (2006). Causal role of Helicobacter pylori infection in gastric cancer: an Asian enigma. World J Gastroenterol, 12, 1346-51.
  33. Sumathi B, Ramalingam S, Navaneethan U, et al (2009). Risk factors for gastric cancer in South India. Singapore Med J, 50, 147-51.
  34. Tredaniel J, Boffetta P, Buiatti E, et al (1997). Tobacco smoking and gastric cancer: review and meta-analysis. Int J Cancer, 72, 565-73.<565::AID-IJC3>3.0.CO;2-O
  35. Tripathi S, Ghoshal U, Mittal B, et al (2011). Association between gastric mucosal glutathione-S-transferase activity, glutathione-S-transferase gene polymorphisms and Helicobacter pylori infection in gastric cancer. Indian J Gastroenterol, 30, 257-63.
  36. Wang KY, Lin JT, Chen CJ, et al (1998). The relationship between the genotypes of cancer susceptibility genes and the development of gastric cancer. China J Public Health, 17, 226-41.
  37. Wiencke JK, Pemble S, Ketterer B, et al (1995). Gene deletion of glutathione S-transferase theta: correlation with induced genetic damage and potential role in endogenous mutagenesis. Cancer Epidemiol Biomarkers and Prev, 4, 253-9.
  38. Xue FB, Xu YY, Wan Y, et al (2001). Association of H. pylori infection with gastric carcinoma: a Meta analysis. World J Gastroenterol, 7, 801-4.
  39. Yadav DS, Devi TR, Ihsan R, et al (2010). Polymorphisms of glutathione-S-transferase genes and the risk of aerodigestive tract cancers in the Northeast Indian population. Genet Test Mol Biomarkers, 14, 715-23.
  40. You WC, Zhang L, Gail MH, et al (2000). Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors. J Natl Cancer Inst, 92, 1607-12.
  41. Zhang AP, Liu BH, Wang L, et al (2011). Glutathione S-transferase gene polymorphisms and risk of gastric cancer in a chinese population. Asian Pac J Cancer Prev, 12, 3421-5.

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