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Glutathione S-Transferase M1 Null Genotype Associated with Gastric Cancer Among Asians

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Abstract

Purpose

The Glutathione S-transferases (GSTs) play multiple roles in the pathogenesis and treatment of cancer. Studies investigating the association between Glutathione S-transferase M1 (GSTM1) null genotype and gastric cancer risk report conflicting results. The purpose of this study was to quantitatively summarize the evidence for such a relationship.

Results

This meta-analysis included 35 studies, which included 4,505 gastric cancer cases and 9,062 controls. The combined results based on all studies showed that the GSTM1 null genotype was associated with an increased risk of gastric cancer (OR = 1.15, 95% confidence interval [CI] = 1.02, 1.29). When stratifying for race, results were similar among Asians (OR = 1.24, 95% CI = 1.07, 1.44) except Caucasians (OR = 1.04, 95% CI = 0.88, 1.24). When stratifying by the location, stage, Lauren’s classification, histological differentiation, lymph node metastasis, smoking, and Helicobacter pylori infection of gastric cancer, we observed that patients with diffuse classification had a significantly higher frequency null genotype (OR = 4.80, 95% CI = 1.65,13.94) than those with intestinal classification among Caucasians.

Conclusions

This meta-analysis suggests that the GSTM1 null genotype may be associated with gastric cancer among Asians.

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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  2. Boyle P. Favorable trends in cancer mortality in the European Union but no room for complacency. Ann Oncol. 2008;19:605–606.

    Article  PubMed  CAS  Google Scholar 

  3. Gondos A, Bray F, Brewster DH, et al. Recent trends in cancer survival across Europe between 2000 and 2004: a model-based period analysis from 12 cancer registries. Eur J Cancer. 2008;44:1463–1475.

    Article  PubMed  CAS  Google Scholar 

  4. Karim-Kos HE, de Vries E, Soerjomataram I, et al. Recent trends of cancer in Europe: a combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. Eur J Cancer. 2008;44:1345–1389.

    Article  PubMed  Google Scholar 

  5. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153–156.

    Article  PubMed  CAS  Google Scholar 

  6. Devesa SS, Fraumeni JF Jr. The rising incidence of gastric cardia cancer. J Natl Cancer Inst. 1999;91:747–749.

    Article  PubMed  CAS  Google Scholar 

  7. Gonzalez CA, Sala N, Capella G. Genetic susceptibility and gastric cancer risk. Int J Cancer. 2002;100:249–260.

    Article  PubMed  CAS  Google Scholar 

  8. Soya SS, Vinod T, Reddy KS, Gopalakrishnan S, Adithan C. Genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) and upper aerodigestive tract cancer risk among smokers, tobacco chewers and alcoholics in an Indian population. Eur J Cancer. 2007;43:2698–2706.

    Article  PubMed  CAS  Google Scholar 

  9. La Torre G, Boccia S, Ricciardi G. Glutathione S-transferase M1 status and gastric cancer risk: a meta-analysis. Cancer Lett. 2005;217:53–60.

    Article  PubMed  CAS  Google Scholar 

  10. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634.

    PubMed  CAS  Google Scholar 

  11. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–1101.

    Article  PubMed  CAS  Google Scholar 

  12. Kato S, Onda M, Matsukura N, et al. Helicobacter pylori infection and genetic polymorphisms for cancer-related genes in gastric carcinogenesis. Biomed Pharmacother. 1997;51:145–149.

    Article  PubMed  CAS  Google Scholar 

  13. Chen SY, Liu TY, Shun CT, et al. Modification effects of GSTM1, GSTT1 and CYP2E1 polymorphisms on associations between raw salted food and incomplete intestinal metaplasia in a high-risk area of stomach cancer. Int J Cancer. 2004;108:606–612.

    Article  PubMed  CAS  Google Scholar 

  14. Cai L, Yu S, Chen J. Relationship between glutathione S-transferase M1, T1 genotype and susceptibility to gastric cancer. Zhonghua Yu Fang Yi Xue Za Zhi. 1999;33:331–333.

    PubMed  CAS  Google Scholar 

  15. Setiawan VW, Zhang ZF, Yu GP, et al. GSTP1 polymorphisms and gastric cancer in a high-risk Chinese population. Cancer Causes Control. 2001;12:673–681.

    Article  PubMed  CAS  Google Scholar 

  16. Strange RC, Matharoo B, Faulder GC, et al. The human glutathione S-transferases: a case-control study of the incidence of the GST1 0 phenotype in patients with adenocarcinoma. Carcinogenesis. 1991;12:25–28.

    Article  PubMed  CAS  Google Scholar 

  17. Harada S, Misawa S, Nakamura T, et al. Detection of GST1 gene deletion by the polymerase chain reaction and its possible correlation with stomach cancer in Japanese. Hum Genet. 1992;90:62–64.

    Article  PubMed  CAS  Google Scholar 

  18. Katoh T, Nagata N, Kuroda Y, et al. Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. Carcinogenesis. 1996;17:1855–1859.

    Article  PubMed  CAS  Google Scholar 

  19. Deakin M, Elder J, Hendrickse C, et al. Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers. Carcinogenesis. 1996;17:881–884.

    Article  PubMed  CAS  Google Scholar 

  20. Kato S, Onda M, Matsukura N, et al. Genetic polymorphisms of the cancer-related gene and Helicobacter pylori infection in Japanese gastric cancer patients. An age and gender matched case-control study. Cancer. 1996;77:1654–1661.

    CAS  Google Scholar 

  21. Oda Y, Kobayashi M, Ooi A, Muroishi Y, Nakanishi I. Genotypes of glutathione S-transferase M1 and N-acetyltransferase 2 in Japanese patients with gastric cancer. Gastric Cancer. 1999;2:158–164.

    Article  PubMed  Google Scholar 

  22. Setiawan VW, Zhang ZF, Yu GP, et al. GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population. Cancer Epidemiol Biomarkers Prev. 2000;9:73–80.

    PubMed  CAS  Google Scholar 

  23. Cai L, Yu SZ, Zhang ZF. Glutathione S-transferases M1, T1 genotypes and the risk of gastric cancer: a case-control study. World J Gastroenterol. 2001;7:506–509.

    PubMed  CAS  Google Scholar 

  24. Saadat I, Saadat M. Glutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers. Cancer Lett. 2001;169:21–26.

    Article  PubMed  CAS  Google Scholar 

  25. Lan Q, Chow WH, Lissowska J, et al. Glutathione S-transferase genotypes and stomach cancer in a population-based case-control study in Warsaw, Poland. Pharmacogenetics. 2001;11:655–661.

    Article  PubMed  CAS  Google Scholar 

  26. Gao CM, Takezaki T, Wu JZ, et al. Glutathione-S-transferases M1 (GSTM1) and GSTT1 genotype, smoking, consumption of alcohol and tea and risk of esophageal and stomach cancers: a case-control study of a high-incidence area in Jiangsu Province, China. Cancer Lett. 2002;188:95–102.

    Article  PubMed  CAS  Google Scholar 

  27. Sgambato A, Campisi B, Zupa A, et al. Glutathione S-transferase (GST) polymorphisms as risk factors for cancer in a highly homogeneous population from southern Italy. Anticancer Res. 2002;22:3647–3652.

    PubMed  CAS  Google Scholar 

  28. Wu MS, Chen CJ, Lin MT, et al. Genetic polymorphisms of cytochrome p450 2E1, glutathione S-transferase M1 and T1, and susceptibility to gastric carcinoma in Taiwan. Int J Colorectal Dis. 2002;17:338–343.

    Article  PubMed  Google Scholar 

  29. Choi SC, Yun KJ, Kim TH, et al. Prognostic potential of glutathione S-transferase M1 and T1 null genotypes for gastric cancer progression. Cancer Lett. 2003;195:169–175.

    PubMed  CAS  Google Scholar 

  30. Suzuki S, Muroishi Y, Nakanishi I, Oda Y. Relationship between genetic polymorphisms of drug-metabolizing enzymes (CYP1A1, CYP2E1, GSTM1, and NAT2), drinking habits, histological subtypes, and p53 gene point mutations in Japanese patients with gastric cancer. J Gastroenterol. 2004;39:220–230.

    Article  PubMed  CAS  Google Scholar 

  31. Roth MJ, Abnet CC, Johnson LL, et al. Polymorphic variation of Cyp1A1 is associated with the risk of gastric cardia cancer: a prospective case-cohort study of cytochrome P-450 1A1 and GST enzymes. Cancer Causes Control. 2004;15:1077–1083.

    Article  PubMed  Google Scholar 

  32. Colombo J, Rossit AR, Caetano A, et al. GSTT1, GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population. World J Gastroenterol. 2004;10:1240–1245.

    PubMed  CAS  Google Scholar 

  33. Li H, Chen XL, Li HQ. Polymorphism of CYPIA1 and GSTM1 genes associated with susceptibility of gastric cancer in Shandong Province of China. World J Gastroenterol. 2005;11:5757–5762.

    PubMed  CAS  Google Scholar 

  34. Nan HM, Park JW, Song YJ, et al. Kimchi and soybean pastes are risk factors of gastric cancer. World J Gastroenterol. 2005;11:3175–3181.

    PubMed  CAS  Google Scholar 

  35. Shen J, Wang RT, Xu YC, Wang LW, Wang XR. Interaction models of CYP1A1, GSTM1 polymorphisms and tobacco smoking in intestinal gastric cancer. World J Gastroenterol. 2005;11:6056–6060.

    PubMed  CAS  Google Scholar 

  36. Palli D, Saieva C, Gemma S, et al. GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high-risk Italian population. Int J Cancer. 2005;115:284–289.

    Article  PubMed  CAS  Google Scholar 

  37. Mu LN, Lu QY, Yu SZ, et al. Green tea drinking and multigenetic index on the risk of stomach cancer in a Chinese population. Int J Cancer. 2005;116:972–983.

    Article  PubMed  CAS  Google Scholar 

  38. Tamer L, Ates NA, Ates C, et al. Glutathione S-transferase M1, T1 and P1 genetic polymorphisms, cigarette smoking and gastric cancer risk. Cell Biochem Funct. 2005;23:267–272.

    Article  PubMed  CAS  Google Scholar 

  39. Lai KC, Chen WC, Tsai FJ, et al. Glutathione S-transferase M1 gene null genotype and gastric cancer risk in Taiwan. Hepatogastroenterology. 2005;52:1916–1919.

    PubMed  CAS  Google Scholar 

  40. Nan HM, Song YJ, Yun HY, Park JS, Kim H. Effects of dietary intake and genetic factors on hypermethylation of the hMLH1 gene promoter in gastric cancer. World J Gastroenterol. 2005;11:3834–3841.

    PubMed  CAS  Google Scholar 

  41. Agudo A, Sala N, Pera G, et al. No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2006;15:1043–1045.

    Article  PubMed  CAS  Google Scholar 

  42. Martinez C, Martin F, Fernandez JM, et al. Glutathione S-transferases mu 1, theta 1, pi 1, alpha 1 and mu 3 genetic polymorphisms and the risk of colorectal and gastric cancers in humans. Pharmacogenomics. 2006;7:711–718.

    Article  PubMed  CAS  Google Scholar 

  43. Hong SH, Kim JW, Kim HG, et al. Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) and N-acetyltransferase 2 polymorphisms and the risk of gastric cancer. J Prev Med Pub Health. 2006;39:135–140.

    Google Scholar 

  44. Boccia S, Sayed-Tabatabaei FA, Persiani R, et al. Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population. BMC Cancer. 2007;7:206.

    Article  PubMed  CAS  Google Scholar 

  45. Ruzzo A, Canestrari E, Maltese P, et al. Polymorphisms in genes involved in DNA repair and metabolism of xenobiotics in individual susceptibility to sporadic diffuse gastric cancer. Clin Chem Lab Med. 2007;45:822–828.

    Article  PubMed  CAS  Google Scholar 

  46. Wideroff L, Vaughan TL, Farin FM, et al. GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas. Cancer Detect Prev. 2007;31:233–236.

    Article  PubMed  CAS  Google Scholar 

  47. Masoudi M, Saadat I, Omidvari S, Saadat M. Genetic polymorphisms of GSTO2, GSTM1, and GSTT1 and risk of gastric cancer. Mol Biol Rep. 2009;36:781–784.

    Article  PubMed  CAS  Google Scholar 

  48. Tripathi S, Ghoshal U, Ghoshal UC, et al. Gastric carcinogenesis: possible role of polymorphisms of GSTM1, GSTT1, and GSTP1 genes. Scand J Gastroenterol. 2008;43:431–439.

    Article  PubMed  CAS  Google Scholar 

  49. Al-Moundhri MS, Alkindy M, Al-Nabhani M, et al. Combined polymorphism analysis of glutathione S-transferase M1/G1 and interleukin-1B (IL-1B)/interleukin 1-receptor antagonist (IL-1RN) and gastric cancer risk in an Omani Arab population. J Clin Gastroenterol. 2009;43:152–156.

    Article  PubMed  CAS  Google Scholar 

  50. Martins G, Alves M. Glutathione S transferase mu polymorphism and gastric cancer in the Portuguese population. Biomarkers. 1998;3:441–447.

    Article  CAS  Google Scholar 

  51. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet. 2001;29:306–309.

    Article  PubMed  CAS  Google Scholar 

  52. Zhou Y, Li N, Zhuang W, et al. Interleukin-10–1082 promoter polymorphism associated with gastric cancer among Asians. Eur J Cancer. 2008;44:2648–2654.

    Article  PubMed  CAS  Google Scholar 

  53. Machado JC, Pharoah P, Sousa S, et al. Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology. 2001;121:823–829.

    Article  PubMed  CAS  Google Scholar 

  54. Loder N. Genetic variations can point the way to disease genes. Nature. 1999;401:734.

    Article  PubMed  CAS  Google Scholar 

  55. Schaid DJ, Jacobsen SJ. Biased tests of association: comparisons of allele frequencies when departing from Hardy–Weinberg proportions. Am J Epidemiol. 1999;149:706–711.

    PubMed  CAS  Google Scholar 

  56. Deng HW, Chen WM, Recker RR. Population admixture: detection by Hardy–Weinberg test and its quantitative effects on linkage-disequilibrium methods for localizing genes underlying complex traits. Genetics. 2001;157:885–897.

    PubMed  CAS  Google Scholar 

  57. Agundez JA, Ladero JM. Glutathione S-transferase GSTT1 and GSTM1 allozymes: beyond null alleles. Pharmacogenomics. 2008;9:359–363.

    Article  PubMed  Google Scholar 

  58. Moyer AM, Salavaggione OE, Hebbring SJ, et al. Glutathione S-transferase T1 and M1: gene sequence variation and functional genomics. Clin Cancer Res. 2007;13:7207–7216.

    Article  PubMed  CAS  Google Scholar 

  59. Zhuo W, Wang Y, Zhuo X, et al. CYP1A1 and GSTM1 polymorphisms and oral cancer risk: association studies via evidence-based meta-analyses. Cancer Invest. 2009;27:86–95.

    Article  PubMed  CAS  Google Scholar 

  60. White DL, Li D, Nurgalieva Z, El-Serag HB. Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: a HuGE systematic review and meta-analysis. Am J Epidemiol. 2008;167:377–389.

    Article  PubMed  Google Scholar 

  61. Shi X, Zhou S, Wang Z, Zhou Z, Wang Z. CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis. Lung Cancer. 2008;59:155–163.

    Article  PubMed  Google Scholar 

  62. Ye Z, Song H. Glutathione s-transferase polymorphisms (GSTM1, GSTP1 and GSTT1) and the risk of acute leukaemia: a systematic review and meta-analysis. Eur J Cancer. 2005;41:980–989.

    Article  PubMed  CAS  Google Scholar 

  63. Garcia-Closas M, Malats N, Silverman D, et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet. 2005;366:649–659.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The research of this paper is supported in part by the Chinese Medical Board Grant on Evidence-based Medicine, New York, USA (Grant number: 98-680).

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 37 Guo Xue Rd, 610041, Chengdu, Sichuan Province, China

    Hong Wang, Yong Zhou, Wen Zhuang, Yi-Qiong Yin & **ao-Ting Wu

  2. Chinese Evidence-Based Medicine/Cochrane Center, 610041, Chengdu, China

    Guan-Jian Liu, Tai-**ang Wu, Xun Yao, Liang Du & Mao-Ling Wei

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  1. Hong Wang
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  2. Yong Zhou
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  3. Wen Zhuang
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Correspondence to **ao-Ting Wu.

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Wang, H., Zhou, Y., Zhuang, W. et al. Glutathione S-Transferase M1 Null Genotype Associated with Gastric Cancer Among Asians. Dig Dis Sci 55, 1824–1830 (2010). https://doi.org/10.1007/s10620-009-0971-5

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