Skip to main content
SpringerLink
Log in

Possible Influence of Glutathione S-Transferase GSTT1 Null Genotype on Age of Onset of Sporadic Colorectal Adenocarcinoma

  • Published:
Diseases of the Colon & Rectum

Abstract

INTRODUCTION: Glutathione S-transferase enzymes mediate exposure to cytotoxic and genotoxic agents and may be involved in cancer susceptibility. Both glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The association of glutathione S-transferase null genotype and risk of developing colorectal cancer is not yet fully clarified. METHODS: We tested whether the null genotypes for GSTM1 and GSTT1 genes altered the risk for sporadic colorectal adenocarcinoma in Brazilian patients. Genomic DNA from 102 sporadic colorectal adenocarcinoma patients and 300 controls was analyzed by polymerase chain reaction. RESULTS: Frequencies of GSTM1, GSTT1, and null combined genotypes were similar in patients and controls (49.9 vs. 44.6 percent, 16.6 vs. 17.3 percent, and 8.8 vs. 8 percent, respectively). We found a 1.03-fold (95 percent confidence interval, 0.96–1.10) and 1.08-fold (95 percent confidence interval, 0.99–1.18) increased risk associated with GSTM1 and GSTT1 null genotypes, respectively (P = 0.45 and P = 0.08) and a 1.18-fold (95 percent confidence interval, 0.47–2.90) increased risk associated with the combined null genotype (P = 0.74). The GSTT1 null genotype was more common in patients who were diagnosed before the age of 60 years than in those who were diagnosed at an older age (28.8 vs. 4 percent, respectively; P = 0.0008). CONCLUSIONS: The results suggest that inherited absence of this carcinogen detoxification pathway may not be associated with sporadic colorectal adenocarcinoma in the present cases. However, a higher frequency of GSTT1 null genotype in patients diagnosed before the age of 60 years suggests that this genotype could influence the age of disease onset in Brazil.

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. DM Parkin P Pisani J Ferlay (1993) ArticleTitleEstimates of the worldwide incidence of eighteen major cancers in 1985 Int J Cancer 54 594–606

    Google Scholar 

  2. P Herrero-Jimenez A Tomita-Mitchell EE Furth S Morgenthaler WG Thilly (2000) ArticleTitlePopulation risk and physiological rate parameters for colon cancer. The union of an explicit model for carcinogenesis with the public health records of the United States Mutat Res 447 73–116

    Google Scholar 

  3. MH Schiffman JS Felton (1990) ArticleTitleRe Am J Epidemiol 131 376–378

    Google Scholar 

  4. M Gerhardsson de Verdier U Hagman RK Peters G Steineck E Overvik (1991) ArticleTitleMeat, cooking methods and colorectal cancer Int J Cancer 49 520–525

    Google Scholar 

  5. E Giovanucci (2001) ArticleTitleAn updated review of the epidemiological evidence that cigarette smoking increases risk of colorectal cancer Cancer Epidemiol Biomarkers Prev 10 725–731

    Google Scholar 

  6. P Terry A Ekbom P Lichtenstein M Feychting A Wolk (2001) ArticleTitleLong-term tobacco smoking and colorectal cancer in a prospective cohort study Int J Cancer 91 585–587

    Google Scholar 

  8. GM Swanson SH Belle RW Burrows (1985) ArticleTitleColon cancer incidence among model markers and pattern markers in the automobile manufacturing industry J Occup Med 27 567–569

    Google Scholar 

  9. B Ketterer (1988) ArticleTitleProtective role of glutathione transferases in mutagenesis and carcinogenesis Mutat Res 202 343–361

    Google Scholar 

  10. JD Hayes DJ Pulford (1995) ArticleTitleThe glutathione S-transferase supergene family Crit Rev Biochem Mol Biol 30 445–600

    Google Scholar 

  11. VR Arruda CE Grignoli MS Gonçalves et al. (1998) ArticleTitlePrevalence of homozygosity for the deleted alleles of glutathione S-transferase mu (GSTM1) and theta (GSTT1) among distinct ethnic groups from Brazil Clin Genet 54 210–214

    Google Scholar 

  12. JG Hengstler M Arand ME Herrero F Oesch (1998) ArticleTitlePolymorphisms of N-acetyltransferases, glutathione S-transferase, microsomal epoxide hydrolase and sulfotransferases Recent Results Cancer Res 154 47–85

    Google Scholar 

  13. VR Arruda CS Lima CR Grignoli et al. (2000) ArticleTitleIncreased risk for acute myeloid leukaemia in individuals with glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) gene defects Eur J Haematol 66 383–388

    Google Scholar 

  14. SC Cotton L Sharp J Little N Brockton (2000) ArticleTitleGlutathione S-transferase polymorphisms and colorectal cancer Am J Epidemiol 151 7–31

    Google Scholar 

  15. S Zhong AH Wyllie D Barnes CR Wolf NK Spurr (1993) ArticleTitleRelationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer Carcinogenesis 14 1821–1824

    Google Scholar 

  16. G Chenevix-Trench J Young M Coggan P Board (1995) ArticleTitleGlutathione S-transferase M1 and T1 polymorphisms Carcinogenesis 16 1655–1657

    Google Scholar 

  17. M Deakin J Elder C Hendrickse et al. (1996) ArticleTitleGlutathione S-transferase GSTT1 genotypes and susceptibility to cancer Carcinogenesis 17 881–884

    Google Scholar 

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

    Google Scholar 

  19. WJ Butler P Ryan IC Roberts-Thompson (1997) ArticleTitleMetabolic genotypes and risk for colorectal cancer increased risk in individuals with glutathione transferase theta 1 (GSTT1) gene defect [abstract] Gastroenterology 112 542–1859

    Google Scholar 

  20. DM Gertig M Stampfer C Haiman CH Hennekens K Kelsey DJ Hunter (1998) ArticleTitleGlutathione S-transferase GSTM1 and GSTT1 polymorphisms and colorectal cancer risk Cancer Epidemiol Biomarkers Prev 7 1001–1005

    Google Scholar 

  21. E Lee Y Huang B Zhao F Seow-Choen A Balakrishnan SH Chan (1998) ArticleTitleGenetic polymorphism of conjugating enzymes and cancer risk J Toxicol Sci 23 140–142

    Google Scholar 

  22. ML Slattery JD Potter W Samowitz J Bigler B Caan M Leppert (1998) ArticleTitleNAT2, GSTM1, cigarette smoking, and risk of colon cancer Cancer Epidemiol Biomarkers Prev 7 1079–1084

    Google Scholar 

  23. H Zhang A Ashmadi G Arbman et al. (1999) ArticleTitleGlutathione S-transferase T1 and M1 genotypes in normal mucosa, transitional mucosa and colorectal adenocarcinoma Int J Cancer 84 135–138

    Google Scholar 

  24. ML Slattery H Kampman W Samowitz BJ Caan JD Potter (2000) ArticleTitleInterplay between dietary inducers of GST and the GSTM1 genotype in colon cancer Int J Cancer 87 728–733

    Google Scholar 

  25. WJ Butler P Ryan IC Roberts-Thomson (2001) ArticleTitleMetabolic genotypes and risk for colorectal cancer J Gastroenterol Hepatol 16 631–635

    Google Scholar 

  26. A Loktionov MA Watson M Gunter WS Stebbings CT Speakman SA Bingham (2001) ArticleTitleGlutathione S-transferase gene polymorphisms in colorectal cancer patients Carcinogenesis 22 1053–1060

    Google Scholar 

  27. I Saadat M Saadat (2001) ArticleTitleGlutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers Cancer Lett 169 21–26

    Google Scholar 

  28. RS Houlston IP Tomlinson (2001) ArticleTitlePolymorphisms and colorectal tumor risk Gastroenterology 121 282–301

    Google Scholar 

  29. J Alves-Silva M Silva-Santos PE Guimaraes et al. (2000) ArticleTitleThe ancestry of Brazilian mtDNA lineages Am J Hum Genet 67 444–461

    Google Scholar 

  30. DR Carvalho-Silva FR Santos J Rocha SD Pena (2001) ArticleTitleThe phylogeography of Brazilian Y-chromosome lineages Am J Hum Genet 68 281–286

    Google Scholar 

  31. BB Duncan MI Schmidt CA Polanczyk SS Mengue (1992) ArticleTitleAltos coeficientes de mortalidade em populações adultas brasileiras—uma comparação internacional Rev Assoc Med Bras 38 138–144

    Google Scholar 

  32. PG Shields (1993) ArticleTitleMolecular epidemiology and the genetics of environmental cancer JAMA 266 681–687

    Google Scholar 

  33. MA Ruiz LG Augusto J Vassallo I Lorand-Metze CA Souza (1994) ArticleTitleBone marrow morphology in patients with neutropenia due to chronic exposure to organic solvents Pathol Res Pract 190 151–154

    Google Scholar 

  34. ML Queiroz C Bincoleto RC Perlingeiro CA Souza H Toledo (1997) ArticleTitleDefective neutrophil function in workers occupationally exposed to hexachlorobenzene Human Exp Toxicol 16 322–326

    Google Scholar 

  35. AC Broders (1925) ArticleTitleThe grading of carcinoma Minn Med 8 726–730

    Google Scholar 

  36. VB Astler FA Coller (1954) ArticleTitleThe prognostic significance of direct extension of carcinoma of the colon and rectum Ann Surg 139 846–851

    Google Scholar 

  38. RK Saiki DH Gelfand S Stoffel et al. (1988) ArticleTitlePrimer-directed enzymatic amplification of DNA with a thermostable DNA polymerase Science 239 487–491

    Google Scholar 

  39. KE Comstock BJ Sanderson G Clafin WD Hener (1990) ArticleTitleGST1 gene deletion determined by polymerase chain reaction Nucleic Acids Res 18 3670–3676

    Google Scholar 

  40. S Pemble KR Schroeder SR Spencer et al. (1994) ArticleTitleHuman glutathione S-transferase theta (GSTT1) Biochem J 300 271–276

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Internal Medicine and Digestive Surgery and the Hematology and Hemotherapy Center, State University of Campinas, Campinas, São Paulo, Brazil

    Helvia Nascimento B.Sc., Claudio S. R. Coy M.D., Ph.D., Maria T. Teori M.T., Ilka F. S. F. Boin M.D., Ph.D., Juvenal R. N. Góes M.D., Ph.D., Fernando F. Costa M.D., Ph.D. & Carmen S. P. Lima M.D., Ph.D.

Authors
  1. Helvia Nascimento B.Sc.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claudio S. R. Coy M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria T. Teori M.T.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ilka F. S. F. Boin M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juvenal R. N. Góes M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fernando F. Costa M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carmen S. P. Lima M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Nascimento, H., Coy, C.S., Teori, M.T. et al. Possible Influence of Glutathione S-Transferase GSTT1 Null Genotype on Age of Onset of Sporadic Colorectal Adenocarcinoma. Dis Colon Rectum 46, 510–515 (2003). https://doi.org/10.1007/s10350-004-6591-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10350-004-6591-4

Keywords

Search

Navigation