Skip to main content

Advertisement

SpringerLink
Log in

GSTM1 and GSTT1 Polymorphisms, Cigarette Smoking, and Risk of Colon Cancer: A Population-based Case-control Study in North Carolina (United States)

  • Original Paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Cigarette smoke is a risk factor for colon cancer, but the importance of dose and interaction with genetic susceptibility remain poorly understood. We used data from a population-based case control study, to examine the association between cigarette smoking and colon cancer in African Americans and whites, and colon cancer and polymorphisms in GSTM1 and GSTT1. A total of 554 cases of primary colon cancer and 874 controls were included in this analysis. We found no association between cigarette smoking (ever versus never) and colon cancer in African Americans (odds ratio (OR)=0.93, 95% confidence interval (CI)=0.65–1.33). In contrast, there was an increased risk of cigarette smoking in whites (OR=1.43, CI=1.05–1.94). There was a small increased risk of colon cancer for individuals with GSTM1 null (African Americans, OR=1.43, CI, 0.98–2.09; whites, OR=1.19, CI, 0.90–1.58) and a decreased risk of colon cancer for individuals with GSTT1 null (African Americans, OR=0.59, CI: 0.40–0.86; whites, OR=0.72, CI: 0.53–1.00). There were weak interactions between GSTT1 null and cigarette smoking in whites, and GSTM1 null genotype and cigarette smoking in African Americans. GSTT1 and GSTM1 polymorphisms may be weakly related to colon cancer risk and there may be racial differences in gene-smoking interactions.

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.

Similar content being viewed by others

References

  1. ACS, Society AC (2003) Cancer Facts and Figures-2003. American Cancer Society, Atlanta

  2. ACS, Society AC (2002) Cancer Facts and Figures-2002. American Cancer Society, Atlanta

  3. CDC, Prevention CfDCa (2000) Behavior Risk Factor Surveillance System CD-ROM 1999. National Center for Disease Prevention and Health Promotion, Atlanta, GA

  4. Barrowman JA, Rahman A, Lindstrom MB, Borgstrom B (1989) Intestinal absorption and metabolism of hydrocarbons. Prog Lipid Res 28(3):189–203

    CAS  PubMed  Google Scholar 

  5. Alexandrov K, Rojas M, Kadlubar FF, Lang NP, Bartsch H (1996) Evidence of anti-benzo[a]pyrene diolepoxide-DNA adduct formation in human colon mucosa. Carcinogenesis 17(9):2081–2083

    CAS  PubMed  Google Scholar 

  6. Savela K, Hemminki K (1991) DNA adducts in lymphocytes and granulocytes of smokers and nonsmokers detected by the 32P-postlabelling assay. Carcinogenesis 12(3):503–508

    CAS  PubMed  Google Scholar 

  7. Rojas M, Alexandrov K, Auburtin G, et al. (1995) Anti-benzo[a]pyrene diolepoxide-DNA adduct levels in peripheral mononuclear cells from coke oven workers and the enhancing effect of smoking. Carcinogenesis 16(6):1373–1376

    CAS  PubMed  Google Scholar 

  8. Arnould JP, Hermant A, Levi-Valensi P, Belegaud J (1998) Detection of benzo[a]pyrene-DNA adducts from leukocytes from heavy smokers. Pathol Biol (Paris) 46(10):787–790

    CAS  Google Scholar 

  9. Shinozaki R, Inoue S, Choi KS, Tatsuno T (1999) Association of benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid (BPDE-DNA) adduct level with aging in male smokers and nonsmokers. Arch Environ Health 54(2):79–85

    CAS  PubMed  Google Scholar 

  10. Hoffmann D, Hoffmann I, El-Bayoumy K (2001) The less harmful cigarette: a controversial issue. a tribute to Ernst L. Wynder. Chem Res Toxicol 14(7):767–790

    Article  CAS  PubMed  Google Scholar 

  11. Bol SA, Horlbeck J, Markovic J, de Boer JG, Turesky RJ, Constable A (2000) Mutational analysis of the liver, colon and kidney of Big Blue rats treated with 2-amino-3-methylimidazo[4,5-f]quinoline. Carcinogenesis 21(1):1–6

    Article  CAS  PubMed  Google Scholar 

  12. Stuart GR, de Boer JG, Haesevoets R, et al. (2001) Mutations induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in cecum and proximal and distal colon of lacI transgenic rats. Mutagenesis 16(5):431–437

    Article  CAS  PubMed  Google Scholar 

  13. Dingley KH, Curtis KD, Nowell S, Felton JS, Lang NP, Turteltaub KW (1999) DNA and protein adduct formation in the colon and blood of humans after exposure to a dietary-relevant dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Epidemiol Biomarkers Prev 8(6):507–512

    CAS  PubMed  Google Scholar 

  14. Giovannucci E, Martinez ME (1996) Tobacco, colorectal cancer, and adenomas: a review of the evidence. J Natl Cancer Inst 88(23):1717–1730

    CAS  PubMed  Google Scholar 

  15. Kahn HA (1966) The Dorn study of smoking and mortality among U.S. veterans: report on eight and one-half years of observation.Natl Cancer Inst Monogr 19:1–125

    CAS  PubMed  Google Scholar 

  16. Doll R, Gray R, Hafner B, Peto R (1980) Mortality in relation to smoking: 22 years’ observations on female British doctors. Br Med J 280(6219):967–971

    CAS  PubMed  Google Scholar 

  17. Rogot E, Murray JL (1980) Smoking and causes of death among U.S. veterans: 16 years of observation. Public Health Rep 95(3):213–222

    CAS  PubMed  Google Scholar 

  18. Doll R, Peto R (1977) Mortality among doctors in different occupations. Br Med J 1(6074):1433–1436

    CAS  PubMed  Google Scholar 

  19. Sturmer T, Glynn RJ, Lee IM, Christen WG, Hennekens CH (2000) Lifetime cigarette smoking and colorectal cancer incidence in the Physicians’ Health Study I. J Natl Cancer Inst 92(14):1178–1181

    Article  CAS  PubMed  Google Scholar 

  20. Wu AH, Paganini-Hill A, Ross RK, Henderson BE (1987) Alcohol, physical activity and other risk factors for colorectal cancer: a prospective study. Br J Cancer 55(6):687–694

    CAS  PubMed  Google Scholar 

  21. Heineman EF, Zahm SH, McLaughlin JK, Vaught JB (1994) Increased risk of colorectal cancer among smokers: results of a 26-year follow-up of US veterans and a review. Int J Cancer 59(6):728–738

    CAS  PubMed  Google Scholar 

  22. Giovannucci E, Colditz GA, Stampfer MJ, et al. (1994) A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in US women. J Natl Cancer Inst 86(3):192–199

    CAS  PubMed  Google Scholar 

  23. Giovannucci E, Rimm EB, Stampfer MJ, et al. (1994) A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in US men. J Natl Cancer Inst 86(3):183–191

    CAS  PubMed  Google Scholar 

  24. Le Marchand L, Wilkens LR, Kolonel LN, Hankin JH, Lyu LC (1997) Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer. Cancer Res 57(21):4787–4794

    CAS  PubMed  Google Scholar 

  25. Slattery ML, Potter JD, Friedman GD, Ma KN, Edwards S (1997) Tobacco use and colon cancer. Int J Cancer 70(3):259–264

    Article  CAS  PubMed  Google Scholar 

  26. Hsing AW, McLaughlin JK, Chow WH, et al. (1998) Risk factors for colorectal cancer in a prospective study among U.S. white men. Int J Cancer 77(4):549–553

    Article  CAS  PubMed  Google Scholar 

  27. Chao A, Thun MJ, Jacobs EJ, Henley SJ, Rodriguez C, Calle EE (2000) Cigarette smoking and colorectal cancer mortality in the cancer prevention study II. J Natl Cancer Inst 92(23):1888–1896

    Article  CAS  PubMed  Google Scholar 

  28. Mannervik B, Alin P, Guthenberg C, et al. (1985) Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci U S A 82(21):7202–7206

    CAS  PubMed  Google Scholar 

  29. Singhal SS, Saxena M, Awasthi S, Ahmad H, Sharma R, Awasthi YC (1992) Gender related differences in the expression and characteristics of glutathione S-transferases of human colon. Biochim Biophys Acta 1171(1):19–26

    CAS  PubMed  Google Scholar 

  30. Butkiewicz D, Grzybowska E, Phillips DH, Hemminki K, Chorazy M (2000) Polymorphisms of the GSTP1 and GSTM1 genes and PAH-DNA adducts in human mononuclear white blood cells. Environ Mol Mutagen 35(2):99–105

    Article  CAS  PubMed  Google Scholar 

  31. Cotton SC, Sharp L, Little J, Brockton N (2000) Glutathione S-transferase polymorphisms and colorectal cancer: a HuGE review. Am J Epidemiol 151(1):7–32

    CAS  PubMed  Google Scholar 

  32. Bolt HM (1994) Genetic and individual differences in the process of biotransformation and their relevance for occupational medicine. Med Lav 85(1):37–48

    CAS  PubMed  Google Scholar 

  33. 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(1):271–276

    CAS  PubMed  Google Scholar 

  34. Wiencke JK, Pemble S, Ketterer B, Kelsey KT (1995) Gene deletion of glutathione S-transferase theta: correlation with induced genetic damage and potential role in endogenous mutagenesis. Cancer Epidemiol Biomarkers Prev 4(3):253–259

    CAS  PubMed  Google Scholar 

  35. Ye Z, Parry JM (2003) A meta-analysis of 20 case-control studies of the glutathione S-transferase M1 (GSTM1) status and colorectal cancer risk. Med Sci Monit 9(10):SR83–SR91

    CAS  PubMed  Google Scholar 

  36. Freedman AN, Michalek AM, Marshall JR, et al. (1996) The relationship between smoking exposure and p53 overexpression in colorectal cancer. Br J Cancer 73(8):902–908

    CAS  PubMed  Google Scholar 

  37. Slattery ML, Potter JD, Samowitz W, Bigler J, Caan B, Leppert M (1998) NAT2, GSTM-1, cigarette smoking, and risk of colon cancer. Cancer Epidemiol Biomarkers Prev 7(12):1079–1084

    CAS  PubMed  Google Scholar 

  38. Slattery ML, Kampman E, Samowitz W, Caan BJ, Potter JD (2000) Interplay between dietary inducers of GST and the GSTM-1 genotype in colon cancer. Int J Cancer 87(5):728–733

    Article  CAS  PubMed  Google Scholar 

  39. Slattery ML, Curtin K, Ma K, Schaffer D, Potter J, Samowitz W (2002) GSTM-1 and NAT2 and genetic alterations in colon tumors. Cancer Causes Control 13(6):527–534

    Article  CAS  PubMed  Google Scholar 

  40. Tiemersma EW, Kampman E, Bueno de Mesquita HB, et al. (2002) Meat consumption, cigarette smoking, and genetic susceptibility in the etiology of colorectal cancer: results from a Dutch prospective study. Cancer Causes Control 13(4):383–393

    Article  PubMed  Google Scholar 

  41. Le Marchand L, Hankin JH, Pierce LM, et al. (2002) Well-done red meat, metabolic phenotypes and colorectal cancer in Hawaii. Mutat Res 506(507):205–214

    PubMed  Google Scholar 

  42. Butler LM, Sinha R, Millikan RC, et al. (2003) Heterocyclic amines, meat intake, and association with colon cancer in a population-based study. Am J Epidemiol 157(5):434–445

    Article  CAS  PubMed  Google Scholar 

  43. Weinberg CR, Sandler DP (1991) Randomized recruitment in case-control studies. Am J Epidemiol 134(4):421–432

    CAS  PubMed  Google Scholar 

  44. Wacholder S, Weinberg CR (1994) Flexible maximum likelihood methods for assessing joint effects in case-control studies with complex sampling. Biometrics 50(2):350–357

    CAS  PubMed  Google Scholar 

  45. SAS, Institutes. In: 8.2 V, editor. Cary, NC, 2001

  46. Darroch J (1997) Biologic synergism and parallelism. Am J Epidemiol 145(7):661–668

    CAS  PubMed  Google Scholar 

  47. Rothman KJ, Greenland S (1998) Modern Epidemiology 2. Lippincott-Raven Publishers, Philadelphia

    Google Scholar 

  48. Millikan RC, Pittman GS, Newman B, et al. (1998) Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 7(5):371–378

    CAS  PubMed  Google Scholar 

  49. Gertig DM, Stampfer M, Haiman C, Hennekens CH, Kelsey K, Hunter DJ (1998) Glutathione S-transferase GSTM1 and GSTT1 polymorphisms and colorectal cancer risk: a prospective study Cancer Epidemiol Biomarkers Prev 7(11):1001–1005

    CAS  PubMed  Google Scholar 

  50. Abdel-Rahman SZ, Soliman AS, Bondy ML, et al. (1999) Polymorphism of glutathione S-transferase loci GSTM1 and GSTT1 and susceptibility to colorectal cancer in Egypt. Cancer Lett 142(1):97–104

    Article  CAS  PubMed  Google Scholar 

  51. Chenevix-Trench G, Young J, Coggan M, Board P (1995) Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset. Carcinogenesis 16(7):1655–1657

    CAS  PubMed  Google Scholar 

  52. Deakin M, Elder J, Hendrickse C, et al. (1996) Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers. Carcinogenesis 17(4):881–884

    CAS  PubMed  Google Scholar 

  53. Welfare M, Monesola Adeokun A, Bassendine MF, Daly AK (1999) Polymorphisms in GSTP1, GSTM1, and GSTT1 and susceptibility to colorectal cancer. Cancer Epidemiol Biomarkers Prev 8(4–1):289–292

    CAS  PubMed  Google Scholar 

  54. Butler WJ, Ryan P, Roberts-Thomson IC (2001) Metabolic genotypes and risk for colorectal cancer. J Gastroenterol Hepatol 16(6):631–635

    Article  CAS  PubMed  Google Scholar 

  55. Saadat I, Saadat M (2001) Glutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers. Cancer Lett 169(1):21–26

    Article  CAS  PubMed  Google Scholar 

  56. Loktionov A, Watson MA, Gunter M, Stebbings WS, Speakman CT, Bingham SA (2001) Glutathione-S-transferase gene polymorphisms in colorectal cancer patients: interaction between GSTM1 and GSTM3 allele variants as a risk-modulating factor. Carcinogenesis 22(7):1053–1060

    Article  CAS  PubMed  Google Scholar 

  57. Laso N, Lafuente MJ, Mas S, et al. (2002) Glutathione S-transferase (GSTM1 and GSTT1)-dependent risk for colorectal cancer. Anticancer Res 22(6):3399–3403

    CAS  PubMed  Google Scholar 

  58. 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(9):1855–1859

    CAS  PubMed  Google Scholar 

  59. Sachse C, Smith G, Wilkie MJ, et al. (2002) A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis 23(11):1839–1849

    Article  CAS  PubMed  Google Scholar 

  60. Nascimento H, Coy CS, Teori MT, et al. (2003) Possible influence of glutathione S-transferase GSTT1 null genotype on age of onset of sporadic colorectal adenocarcinoma. Dis Colon Rectum 46(4):510–515

    Article  PubMed  Google Scholar 

  61. van der Hel OL, Bueno de Mesquita HB, Roest M, et al. (2003) No modifying effect of NAT1, GSTM1, and GSTT1 on the relation between smoking and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 12(7):681–682

    PubMed  Google Scholar 

  62. Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK (1993) Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14(9):1821–1824

    CAS  PubMed  Google Scholar 

  63. Kiss I, Sandor J, Pajkos G, Bogner B, Hegedus G, Ember I (2000) Colorectal cancer risk in relation to genetic polymorphism of cytochrome P450 1A1, 2E1, and glutathione-S-transferase M1 enzymes. Anticancer Res 20(1B):519–522

    CAS  PubMed  Google Scholar 

  64. Lee E, Huang Y, Zhao B, Seow-Choen F, Balakrishnan A, Chan SH (1998) Genetic polymorphism of conjugating enzymes and cancer risk: GSTM1, GSTT1, NAT1 and NAT2. J Toxicol Sci 23(2):140–142

    PubMed  Google Scholar 

  65. Hallier E, Langhof T, Dannappel D, et al. (1993) Polymorphism of glutathione conjugation of methyl bromide, ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchanges (SCE) in lymphocytes. Arch Toxicol 67(3):173–178

    Article  CAS  PubMed  Google Scholar 

  66. Landi S (2000) Mammalian class theta GST and differential susceptibility to carcinogens: a review. Mutat Res 463(3):247–283

    CAS  PubMed  Google Scholar 

  67. Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30(6):445–600

    CAS  PubMed  Google Scholar 

  68. Thier R, Pemble SE, Kramer H, Taylor JB, Guengerich FP, Ketterer B (1996) Human glutathione S-transferase T1–1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium. Carcinogenesis 17(1):163–166

    CAS  PubMed  Google Scholar 

  69. BRFSS (2001) North Carolina Behavioral Risk Factor Surveillance System survey. North Carolina Department of Public Health, 2002, Raileigh.

Download references

Acknowledgements

This research was supported in part by grants from the National Institutes of Health (R01 CA66635 and P30 DK34987). These analyses were conducted while Dr. Kui Huang was a National Institutes of Health predoctoral trainee (5-T32-ES07018) at University of North Carolina-Chapel Hill. We thank the study participants, physicians, interviewers, phlebotomists, and staff of North Carolina Colon Cancer Study. We would like to acknowledge the contribution of Dr. Andy F. Olshan to data analyses.

Author information

Authors and Affiliations

  1. Global Epidemiology, Pfizer Inc., Mail stop: 150/3/80, 235 East 42nd Street, New York City, NY, 10017-575, USA

    Kui Huang

  2. Department of Epidemiology, University of North Carolina-Chapel Hill, North Carolina, USA

    Robert S. Sandler, Robert C. Millikan, Jane C. Schroeder & Kari E. North

  3. Department of Cancer Biology, Wake Forest University, North Carolina, USA

    Jennifer Hu

Authors
  1. Kui Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert S. Sandler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert C. Millikan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jane C. Schroeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kari E. North
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jennifer Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kui Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, K., Sandler, R.S., Millikan, R.C. et al. GSTM1 and GSTT1 Polymorphisms, Cigarette Smoking, and Risk of Colon Cancer: A Population-based Case-control Study in North Carolina (United States). Cancer Causes Control 17, 385–394 (2006). https://doi.org/10.1007/s10552-005-0424-1

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-005-0424-1

Keywords

Search

Navigation