Skip to main content
SpringerLink
Log in

Association of GSTM1, GSTT1, GSTP1 and CYP2E1 Single Nucleotide Polymorphisms with Colorectal Cancer in Iran

  • Research
  • Published:
Pathology & Oncology Research

Abstract

Colorectal cancer is a major cause of morbidity and mortality both globally and in Iran. The aim of this study was to determine the association between genetic polymorphisms of glutathione S-transferases P1, M1 and T1 (GSTP1, M1, T1) and susceptibility to colorectal cancer (CRC). Genotyping of GSTP1, GSTM1 and GSTT1 was performed by the use of pyrosequencing. One hundred cases and healthy controls were enrolled into this study. Mean GSTT1 polymorphism type was significantly (P < 0.01) higher in cases as compared to controls (P < 0.0001: OR, 2.43: 95% CI, 1.47-4). On the other hand there is no significant association between GSTM1, GSTP1 and colorectal cancer. GSTs measurement may be useful as a colorectal marker in colorectal cancer and biopsies obtained at colonoscopy can be used to measure tumor markers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Guengerich FP (1992) Metabolic activation of carcinogens. Pharmacol Ther 54:17–61

    Article  PubMed  CAS  Google Scholar 

  2. Guengerich FP, Shimada T (1991) Oxidation of toxic and carcinogenic chemicals by human cytochrome P- 450 enzymes. Chem Res Toxicol 4:391–407

    Article  PubMed  CAS  Google Scholar 

  3. Doll R, Peto R (1981) The causes of cancers: quantitative estimates of avoidable risks of cancers in the United States today. J Natl Cancer Inst 66(6):1191–1308

    PubMed  CAS  Google Scholar 

  4. Chasseaud LF (1979) The role of glutathione and glutathione S_transferases in the metabolism of chemical carcinogens and other electrophiles agents. Adv Cancer Res 29:175–274

    Article  PubMed  CAS  Google Scholar 

  5. Coles B, Ketterer B (1990) The role of glutathione transferases in chemical carcinogenesis. Crit Rev Biochem MolBiol 25:47–70

    Article  CAS  Google Scholar 

  6. Mucci LA, Wedren S, Tamimi RM, Trichopoulos D, Adami HO (2001) The role of gene-environment interaction in the aetiology of human cancer: examples from cancers of the large bowel, lung and breast. J Intern Med 249:477–493

    Article  PubMed  CAS  Google Scholar 

  7. Kihara M, Kihara M, Noda K (1995) Risk of smoking for squamous and small cell carcinomas of the lung modulated by combinations of CYP1A1 and GSTM1 gene polymorphisms in a Japanese population. Carcinogenesis 16:2331–2336

    Article  PubMed  CAS  Google Scholar 

  8. Lin DX, Tang YM, Peng Q, Lu SH, Ambrosone CB, Kadlubar FF (1998) Susceptibility to esophageal cancer and genetic polymorphisms in glutathione s- transferases T1, P1, and M1 and cytochrome P450 2E1. Cancer Epidemiology, Biomarker & Prey 7:1013–1018

    CAS  Google Scholar 

  9. Nebert DW, McKinnon RA, Puga A (1996) Human drug- metabolizing enzyme polymorphisms: effects on risk of toxicity and cancer. DNA Cell Biol 15:273–280

    Article  PubMed  CAS  Google Scholar 

  10. Cheng KK, Day NE, Duffy SW, Lam TH, Fok M, Wong J (1992) Pickled vegetables in the aetiology of esophageal cancer in Hong Kong Chinese. Lancet 339:1314–1318

    Article  PubMed  CAS  Google Scholar 

  11. Hecht SS (1998) Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosamines. Chem Res Toxicol 11(6):559–603

    Article  PubMed  CAS  Google Scholar 

  12. Guengerich FP, Kim DH, Iwasaki M (1991) Role of human cytochrome P-450IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 4:168–179

    Article  PubMed  CAS  Google Scholar 

  13. Gunter MJ, Watson MA, Loktionov AS et al (2005) No association between cytochrome P450 and glutathione S-transferase gene polymorphisms and risk of colorectal adenoma: results from the UK flexible sigmoidoscopy screening trial. Canc Epidemiol Biomarkers Prev 14(4):1028–30

    Article  CAS  Google Scholar 

  14. Nakajima T, Wang R-S, Nimura Y et al (1996) Expression of cytochrome P450s and glutathione S- transferases in human esophagus with squamous- cell carcinomas. Carcinogenesis 17:1477–1481

    Article  PubMed  CAS  Google Scholar 

  15. Boyer TD, Kenney WC (1985) Preparation, characterization and properties of glutathione S-transferases. In: Zakim D, Vessey D (eds) Biochemical pharmacology and toxicology. Wiley, New York

    Google Scholar 

  16. Mannervik B, Awasthi YC, Board PG et al (1992) Nomenclature for human glutathione S-transferases. Biochem J 282:305–306

    PubMed  CAS  Google Scholar 

  17. Meyer DJ, Coles B, Pemble SE, Gilmore KS, Fraser GM, Ketterer B (1991) θ, a new class of glutathione transferases purified from rat and man. Biochem J 274:409–414

    PubMed  CAS  Google Scholar 

  18. Lin D, Meyer DJ, Ketterer B, Lang NP, Kadlubar FF (1994) Effects of human and rat glutathione S-transferases on the covalent bonding of the N-acetoxy derivatives of heterocyclic amine carcinogens in vitro: a possible mechanism of organ specificity in their carcinogenesis. Cancer Res 54:4920–4926

    PubMed  CAS  Google Scholar 

  19. Pemble S, Schroeder KR, Spenser SR et al (1994) Human glutathione S-transferase (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300:271–276

    PubMed  CAS  Google Scholar 

  20. Evans WE, Relling MV (1999) Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286:487–91

    Article  PubMed  CAS  Google Scholar 

  21. Rebbeck TR (1997) Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomark Prev 6:733–743

    CAS  Google Scholar 

  22. Strange RC, Lear JT, Fryer AA (1998) Glutathione S-transferase polymorphisms: influence on susceptibility to cancer. Chem Biol Interact 24(111–112):351–364

    Article  Google Scholar 

  23. Nomania H, Mohammadzadeh Ghobadloob S, Yaghmaeib B, Rezvaniea NA, Yaghmaeic K (2005) Glutathione S-transferases activity in patients with colorectal cancer. Clin Biochem 38:621–624

    Article  Google Scholar 

  24. Rajagopal R, Deakin M, Fawole AS et al (2005) Glutathione S- transferase T1 polymorphisms are associated with outcome in colorectal cancer. Carcinogenesis 26(12):2157–2163

    Article  PubMed  CAS  Google Scholar 

  25. Srivastava SK, Singhal SS, Hu X, Awasthi YC, Zimniak P, Singh SV (1999) Differential catalytic efficiency of allelic variants of human glutathione S-transferase Pi in catalyzing the glutathione conjugation of thiotepa. Arch Biochem Biophys 366:89–94

    Article  PubMed  CAS  Google Scholar 

  26. Houlston RS (1999) Glutathione S-transferase M1 status and lung cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 8:675–682

    CAS  Google Scholar 

  27. Baily R, Roodi N, Verrier CS, Yee CJ, Dupont WD, Parl F (1998) Breast cancer and CYP1A1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans. Cancer Res 58:65–70

    Google Scholar 

  28. Saadat I, Saadat M (2001) Glutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers. Cancer Letters 169:21–26

    Article  PubMed  CAS  Google Scholar 

  29. de Jong M, Nolte IM, te Meerman GJ et al (2002) Low-penetrance genes and their involvement in colorectal cancer susceptibility. Cancer Epidemiol Biomarkers Prev 11:1332–52

    PubMed  CAS  Google Scholar 

  30. Board PG (1981) Gene deletion and partial deficiency of the glutathione S-transferase (ligandin) system in man. FEBS Lett 135:12–14

    Article  PubMed  CAS  Google Scholar 

  31. Pemble S, Schroeder KR, Spencer SS, Meyer DJ, Hallier E, Bolt HM (1994) Human glutathione S-transferase (GSTT1): cDNA cloning and the characterisation of a genetic polymorphism. Biochem J 300:271–276

    PubMed  CAS  Google Scholar 

  32. Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwini J (1997) Molecular cloning, characterisation and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase π variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem 272:10004–11112

    Article  PubMed  CAS  Google Scholar 

  33. Casson AG, Zheng Z, Chiasson D et al (2003) Associations between genetic polymorphisms of Phase I and II metabolizing enzymes, p53 and susceptibility to esophageal adenocarcinoma. Cancer Detect Prev 27:139–146

    Article  PubMed  CAS  Google Scholar 

  34. Tan W, Song N, Wang GQ et al (2000) Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China. Cancer Epidemiology Biomarkers Prev 9:551–556

    CAS  Google Scholar 

  35. Butler WJ, Ryan P, Roberts-Thomson IC (2001) Metabolic genotypes and risk for colorectal cancer. J Gastroenterology Hepatol 16:631–635

    Article  CAS  Google Scholar 

  36. Lu X M, Zang YM, Lin RY et al (2005) Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh’s esophageal squamous cell cancer in Xinjiang, China. World J Gastroenterol 28: 11(24): 3651-3654.

    Google Scholar 

  37. Xing D, Tan W, Song N, Lin D (2000) Genetic polymorphism in hOGG1and susceptibility to esophageal cancer in Chinese. Zhonghuayixue Yichuanxue Zazhi 17:377–380

    CAS  Google Scholar 

  38. Tan W, Chen GF, Xing DY, Song CY, Kadlubar FF, Lin DX (2001) Frequency of CYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population. Int J Cancer 95:96–101

    Article  PubMed  CAS  Google Scholar 

  39. Tan W, Song N, Wang GQ et al (2000) Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China. Cancer Epidemiol Biomarkers Prev 9:551–556

    PubMed  CAS  Google Scholar 

  40. Dong CH, Yu SZ, Chen GC, Zhao DM, Hu Y (1998) Association of polymorphisms of glutathioneS transferase M1 and T1 genotypes with elevated aflatoxin and increased risk of primary liver cancer. Shijie Huaren Xiaohua Zazhi 6:463–466

    CAS  Google Scholar 

  41. Thong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK (1993) Relationship between the GSTMI genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14:1821–1824

    Article  Google Scholar 

  42. Chevenix-Trench G, Young J, Coggan M, Board P (1995) Glutathione S-transferase Ml, and Tl polymorphisms: susceptibility to colon cancer and age of onset. Carcinogenesis 16:1655–1657

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We thank all members of Lab at Research Center for Gastroenterology and Liver Disease for their helpful comments and constructive discussions on this project and providing grant support as well.

Author information

Authors and Affiliations

  1. Research Center for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Taleghani st- Evin, Tehran, Iran

    Saeideh Ebrahimkhani, Babak Nourinaier, Nasrin Vali & Mohammad Reza Zali

  2. Department of Cell and Molecular Biology, Islamic Azad University, Tonekabon Branch, Tonekabon, Iran

    Ali Mohammad Asgharian

  3. Department of Cell and Molecular Biology, Azarbaijan Tarbiat Molaem University, Tonekabon, Iran

    Fatemeh Abbasi

  4. Zanjan University of Medical Science, Zanjan, Iran

    Khadijeh Ebrahimkhani

Authors
  1. Saeideh Ebrahimkhani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Mohammad Asgharian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Babak Nourinaier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Khadijeh Ebrahimkhani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nasrin Vali
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fatemeh Abbasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohammad Reza Zali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Reza Zali.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ebrahimkhani, S., Asgharian, A.M., Nourinaier, B. et al. Association of GSTM1, GSTT1, GSTP1 and CYP2E1 Single Nucleotide Polymorphisms with Colorectal Cancer in Iran. Pathol. Oncol. Res. 18, 651–656 (2012). https://doi.org/10.1007/s12253-011-9490-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-011-9490-8

Keywords

Search

Navigation