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Cancer Causes & Control

, Volume 13, Issue 6, pp 527–534 | Cite as

GSTM-1 and NAT2 and genetic alterations in colon tumors

  • M.L. Slattery
  • Karen Curtin
  • K Ma
  • Donna Schaffer
  • John Potter
  • Wade Samowitz
Article

Abstract

Objective: Phase II metabolizing enzymes such as glutathione S-transferases and N-acetyltransferase are involved in the detoxification of carcinogens. Genetic variants of genes coding for these enzymes have been evaluated as to their association with colon cancer, both as independent risk factors and as effect modifiers for associations with diet and cigarette smoking. In this study, we evaluate associations between the GSTM-1 genotype and the NAT2-imputed phenotype and acquired mutations in tumors Methods: Data is taken from a set of 1836 cases and 1958 controls with colon cancer who were part of a large case–control study of colon cancer and whose tumors were previously analyzed for Ki-ras, p53, and microsatellite instability (MSI). We also evaluate the modifying effects of these genetic variants with diet and cigarette smoking, factors previously identified as being associated with specific tumor alterations. Results: Neither GSTM-1 nor the NAT2-imputed phenotype was independently associated with Ki-ras, p53, or MSI. Cigarette smoking significantly increased the risk of tumors involving the MSI pathway. Additionally, cigarette smoking doubled the risk of p53 transversion mutations among those who were GSTM-1 present. Cases were slightly more likely to have a p53 mutation if they frequently consumed red meat and had the imputed NAT2 intermediate/rapid phenotype relative to slow phenotype/infrequent consumers of red meat (OR 2.0, 95% CI 1.3–3.0 for intermediate/rapid). Conclusions: These data provide support that diet and cigarette smoking may be associated with specific disease pathways, although GSTM-1 and NAT2 do not independently appear to alter susceptibility to these diet and lifestyle factors.

cigarette smoking colon cancer cruciferous vegetables diet GST Ki-ras MSI NAT2 p53 

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References

  1. 1.
    Whalen R, Boyer TD (1988) Human glutathione S-transferases. Semin Liver Dis 18: 345-358.Google Scholar
  2. 2.
    Caporaso N, Landi MT, Vineis P (1991) Relevance of metabolic polymorphisms to human carcinogenesis: evaluation of epidemiologic evidence. Pharmacogenetics 1: 4-19.Google Scholar
  3. 3.
    Nebert DW, McKinnon R, Puga A (1996) Human drug-metabolizing enzyme polymorphisms: effects on risk of toxicity and cancer. DNACell Biol 15: 273-280.Google Scholar
  4. 4.
    Ketter B (1988) Protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis. Mut Res 202: 343-361. Genetic susceptibility and colon tumor alterations 533Google Scholar
  5. 5.
    Zhong S, Wyllie AH, Barnes D, Wolf CR, Suprr NK (1993) Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast, and colon cancer. Carcinogenesis 14: 1831-1834.Google Scholar
  6. 6.
    Nebert DW (1991) Identification of genetic differences in drug metabolism: prediction of individual risk of toxicity or cancer. Hepatology 14: 398-401.Google Scholar
  7. 7.
    Steinmetzer KA, Potter JD (1991) Vegetables, fruit, and cancer. II. Mechanisms. Cancer Causes Control 2: 427-442.Google Scholar
  8. 8.
    Slattery ML, Kampman E, Samowitz W, Caan BJ, Potter JD (2000) Interplay between dietary activators of GST and the GSTM-1 genotype in colon cancer. Int J Cancer 87: 728-733.Google Scholar
  9. 9.
    Sugimura T, Sato S (1983) Mutagens-carcinogens in foods. Cancer Res 43: 2415s-4221s.Google Scholar
  10. 10.
    IARC (1973) IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Vol. 3: Certain Polycyclic Aromatic Hydrocarbons and Heterocyclic Compounds, Lyon: IARC.Google Scholar
  11. 11.
    Corpet D, Stamp D, Medline A, Minkin S, Archer M, Bruce WR (1990) Promotion of colonic microadenoma growth in mice and rats fed cooked sugar or cooked casein and fat. Cancer Res 50: 6955-6958.Google Scholar
  12. 12.
    Bingham SA, Pignatelli B, Pollock JRA, et al. (1996) Does increased endogenous formation of N-nitroso compounds in the human colon explain the association between red meat and colon cancer? Carcinogenesis 17: 515-523.Google Scholar
  13. 13.
    Slattery ML, Curtin K, Anderson K, et al. (2000) Associations between cigarette smoking, lifestyle factors, and microsatellite instability in colon tumors. J Natl Cancer Inst 92: 1831-1835.Google Scholar
  14. 14.
    Slattery ML, Curtin K, Ma Kn, et al. (2000) Associations between dietary intake and Ki-ras mutations in colon tumors: a populationbased study. Cancer Res 60: 6935-6941.Google Scholar
  15. 15.
    Voskuil DW, Kampman E, van Kraats AA, et al. (1999) p53 overexpression and p53 mutations in colon carcinomas: relation to dietary risk factors. Int J Cancer 81: 675-681.Google Scholar
  16. 16.
    Greenblatt MS, Bennett WP, Hollstein M, Harris CC (1994) Mutations in the p53 tumor-suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54: 4855-4878.Google Scholar
  17. 17.
    Slattery ML, Edwards S, Caan B, Kerber RA, Potter JD (1995) Response rates among control subjects in case-control studies. Ann Epidemiol 5: 245-249.Google Scholar
  18. 18.
    Edwards S, Slattery ML, Mori M, Berry TD, Palmer P (1994) Objective system for interviewer performance evaluation for use in epidemiologic studies. Am J Epidemiol 140: 1020-1028.Google Scholar
  19. 19.
    Slattery ML, Caan B, Duncan D, Berry TD, Coates A, Kerber R (1994) A computerized diet history questionnaire for epidemiologic studies. J Am Diet Assoc 94: 761-766.Google Scholar
  20. 20.
    Liu K, Slattery ML, Jacobs DJ, et al. (1994) A study of the reliability and comparative validity of the CARDIA dietary history. Ethnicity Dis 4: 15-27.Google Scholar
  21. 21.
    Slattery ML, Edwards SL, Palmer L, et al. (2000) Use of archival tissue in epidemiologic studies: collection procedures and assessment of potential sources of bias. Mut Res 432: 7-14.Google Scholar
  22. 22.
    Samowitz WS, Curtin K, Schaffer D, Robertson M, Leppert M, Slattery ML (2000) Relationship of K-ras mutations in colon cancers to tumor location, stage and survival: a population-based study. Cancer Epidemiol Biomarkers Prev 9: 1193-1198.Google Scholar
  23. 23.
    Parsons R, Myeroff L, Liu B, et al. (1995) Microsatellite instability and mutations of the transforming growth factor b type II receptor gene in colorectal cancer. Cancer Res 55: 5548-5550.Google Scholar
  24. 24.
    Samowitz WS, Slattery ML, Potter JD, Leppert MF (1999) BAT-26 and BAT-40 instability in colorectal adenomas and carcinomas and germline polymorphisms. Am J Pathol 154: 1637-1641.Google Scholar
  25. 25.
    Samowitz WS, Slattery ML (1997) Transforming growth factor b receptor type 2 mutations and microsatellite instability in sporadic colorectal adenomas and carcinomas. Am J Pathol 151: 33-35.Google Scholar
  26. 26.
    Brownstein MJ, Carpten JD, Smith JR (1996) Modulation of nontemplated nucleotide addition by Taq DNA polymerase: primer modifications that facilitate genotyping. BioTechniques 20: 1004-1010.Google Scholar
  27. 27.
    Hoang JM, Cottu PH, Thuille B, Salmon RJ, Thomas G, Hamelin R (1997) BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines. Cancer Res 57: 300-303.Google Scholar
  28. 28.
    Kampman E, Slattery ML, Bigler J, et al. (1999) Meat consumption, genetic susceptibility, and colon cancer risk: a US multi-center case-control study. Cancer Epidemiol Biomarkers Prev 8:15-24.Google Scholar
  29. 29.
    Bell DA, Taylor MA, Butler EA, et al. (1993) Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a newslowacetylator allele common in African-Americans. Carcinogenesis 14: 1689-1692.Google Scholar
  30. 30.
    Porbst-Hensch NM, Tannenbaum SR, Chan KK, Coetzee GA, Ross RK, Yu MC (1998) Absence of the glutathione S-transferase M1 gene increases cytochrome p4501A2 activity among frequent consumers of cruciferous vegetables in a Caucasian population. Cancer Epidemiol Biomarkers Prev 7: 635-638.Google Scholar
  31. 31.
    Ketterer B (1998) Dietary isothiocyanates as confounding factors in the molecular epidemiology of colon cancer. Cancer Epidemiol Biomarkers Prev 7: 645-646.Google Scholar
  32. 32.
    Lin HJ, Probst-Hensch NM, Louie AD, et al. (1998) Glutathione transferase null genotype, broccoli, and lower prevalence of colorectal adenomas. Cancer Epidemiol Biomarkers Prev 7: 647-652.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • M.L. Slattery
    • 1
  • Karen Curtin
    • 1
  • K Ma
    • 1
  • Donna Schaffer
    • 2
  • John Potter
    • 3
  • Wade Samowitz
    • 4
  1. 1.Health Research Center, Department of Family and Preventive MedicineUniversity of UtahSalt Lake CityUSA
  2. 2.Kaiser Permanente Medical Care ProgramOaklandUSA
  3. 3.Fred Hutchinson Cancer Research CenterSeattleUSA
  4. 4.Department of Surgical PathologyUniversity of UtahSalt Lake CityUSA

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