Skip to main content

Advertisement

SpringerLink
Log in

Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case–control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455→G), and GSTP1 (A313→G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case–controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76–2.41 and OR = 0.75; 95% CI = 0.41–1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01–3.12 and OR = 1.99; 95% CI = 1.07–3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Greenlee RT, Murray T, Bolden S, Wings PA (2000) Cancer statistics. CA Cancer J Clin 50(1):7

    Article  PubMed  CAS  Google Scholar 

  2. Johansson SL, Cohen SM (1997) Epidemiology and etiology of bladder cancer. Semin Surg Oncol 13:291–298

    Article  PubMed  CAS  Google Scholar 

  3. Zeegers MPA, Tan FES, Dorant E, Van den Brandt P (2000) The impact of characteristics of cigarette smoking on urinary tract cancer risk. A meta-analysis of epidemiologic studies. Cancer 89(3):630–639

    Article  PubMed  CAS  Google Scholar 

  4. Hecht EM (2003) Tobacco carcinogens, their biomarkers and tobacco induced cancer. Nat Rev Cancer 3:733–744

    Article  PubMed  CAS  Google Scholar 

  5. Luch A (2005) Nature and nurture—lessons from chemical carcinogenesis. Nat Rev Cancer 5:113–125

    Article  PubMed  CAS  Google Scholar 

  6. Boffetta P, Jourenkova N, Gustavsson P (1997) Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. Cancer Causes Control 8:444–472

    Article  PubMed  CAS  Google Scholar 

  7. Yu MC, Skipper PL, Tannenbaum SR, Chan KK, Ross RK (2002) Arylamine exposures and bladder cancer risk. Mutat Res 506–507:21–28

    PubMed  Google Scholar 

  8. Patrianakos CHD (1979) Chemical studies on tobacco smoke. LXIUV. On the analysis of aromatic amines in cigarette smoke. J Anal Toxicol 3:150–154

    CAS  Google Scholar 

  9. Ma Q, Lu AYH (2007) CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies. Drug Metab Dispos 35:1009–1016

    Article  PubMed  CAS  Google Scholar 

  10. Shimada T (2006) Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab Pharmacokinet 21:257–276

    Article  PubMed  CAS  Google Scholar 

  11. Song N, Tan W, Xing D, Lin D (2001) CYP1A1 polymorphism and risk of lung cancer in relation to tobacco smoking: a case control study in China. Carcinogenesis 22:11–16

    Article  PubMed  CAS  Google Scholar 

  12. Sato M, Sato T, Izumo T, Amagasa T (1999) Genetic polymorphism of drug-metabolizing enzymes and susceptibility to oral cancer. Carcinogenesis 20(10):1927–1931

    Article  PubMed  CAS  Google Scholar 

  13. Sato M, Sato T, Izumo T, Amagasa T (2000) Genetically high susceptibility to oral squamous cell carcinoma in terms of combined genotyping of CYP1A1 and GSTM1 genes. Oral Oncol 36:267–271

    Article  PubMed  CAS  Google Scholar 

  14. Miller MC, Mohrenweiser HW, Bell DA (2001) Genetic variability in susceptibility and response to toxicants. Toxicol Lett 120(1–3):269–280

    Article  PubMed  CAS  Google Scholar 

  15. Their R, Brüning T, Roos PH, Hans-Peter Rihs PH, Golka K, Ko Y, Bolt HM (2003) Markers of genetics susceptibility in human environmental hygiene and toxicology: the role of selected CYP, Nat and GST genes. Int J Hyg Environ Health 206:149–171

    Article  Google Scholar 

  16. Salagovic J, Kalina I, Habalová V, Hrivnák M, Valanský L, Biros E (1999) The role of human glutathione S-transferases M1 and T1 in individual susceptibility to bladder cancer. Physiol Res 48(6):465–471

    PubMed  CAS  Google Scholar 

  17. Harries LW, Stubbins MJ, Forman D, Howard GCW, Wolf CR (1997) Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 18(4):641–644

    Article  PubMed  CAS  Google Scholar 

  18. Fryer AA, Ramsay HM, Lovatt TJ, Jones PW, Hawley CM, Nicol DL, Strange RC, Harden PN (2005) Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients. Carcinogenesis 26(1):185–191

    Article  PubMed  CAS  Google Scholar 

  19. Gonlugur U, Pinarbasi H, Gonlugur TE, Silig Y (2006) The association between polymorphisms in glutathione S-transferase (GSTM1 and GSTT1) and lung cancer outcome. Cancer Invest 24(5):497–501

    Article  PubMed  CAS  Google Scholar 

  20. Little J, Sharp L, Masson LF, Brockton NT, Cotton SC, Haites NE, Cassidy J (2006) Colorectal cancer and genetic polymorphisms of CYP1A1, GSTM1 and GSTT1: a case-control study in the Grampian region of Scotland. Int J Cancer 119(9):2155–2156

    Article  PubMed  CAS  Google Scholar 

  21. Saad AA, O’Connor PJ, Mostafa MH, Metwalli NE, Cooper DP, Povey AC, Margison GP (2005) Glutathione S-transferase M1, T1 and P1 polymorphisms and bladder cancer risk in Egyptians. Int J Biol Markers 20(1):69–72

    PubMed  CAS  Google Scholar 

  22. Karagas MR, Park S, Warren A, Hamilton J, Nelson HH, Mott LA, Kelsey KT (2005) Gender, smoking, glutathione-S-transferase variants and bladder cancer incidence: a population-based study. Cancer Lett 219(1):63–69

    Article  PubMed  CAS  Google Scholar 

  23. Carrano AV, Natarajan AT (1988) Considerations for population monitoring using cytogenetic techniques. Mutat Res 204:379–406

    Article  PubMed  CAS  Google Scholar 

  24. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extraction DNA from human nucleated cell. Nucleic Acid Res 16:1215

    Article  PubMed  CAS  Google Scholar 

  25. Abdel-Rahman SZ, El-Zein RA, Anwar WA, Au WW (1996) A multiplex PCR procedure for polymorphic analysis of GSTM1 and GSTT1 genes in population studies. Cancer Lett 107(2):229–233

    Article  PubMed  CAS  Google Scholar 

  26. Drakoulis N, Cascorbi I, Brockmöller J, Gross CR, Roots J (1994) Polymorphisms in the human CYP1A1 gene as susceptibility factors for lung cancer: exon-7 mutation (4889 A to G), and T to C mutation in the 3′-flanking region. Clin Investig 72:240–248

    Article  PubMed  CAS  Google Scholar 

  27. Srivastava DS, Mishra DK, Mandhani A, Mittal B, Kumar A, Mittal RD (2005) Association of genetic polymorphism of glutathione S-transferase M1, T1, P1 and susceptibility to bladder cancer. Eur Urol 48(2):339–344

    Article  PubMed  CAS  Google Scholar 

  28. Jeong JH, Kim JH, Seo IY, Kim HJ, Oh GJ, Chae SC, Lim JS, Chung HT, Kim JJ (2003) Association between glutathione S-transferase M1 and T1 polymorphisms and increased risk for bladder cancer in Korean smokers. Cancer Lett 202:193–199

    Article  CAS  Google Scholar 

  29. Pelucchi C, Bosetti C, Negri C, Malvezzi M, La Vecchia C (2006) Mechanisms of disease. The epidemiology of bladder cancer. Nat Clin Pract Urol 3(6):327–340

    Article  PubMed  CAS  Google Scholar 

  30. Moore LE, Wiencke JK, Bates MN, Zheng S, Reym OA, Smith AH (2004) Investigation of genetic polymorphisms and smoking in a bladder cancer case-control study in Argentina. Cancer Lett 211(2):199–207

    Article  PubMed  CAS  Google Scholar 

  31. Ryk C, Berggren P, Kuma R, Hemminki K, Larsson P, Steineck G, Lambert B, Hou SM (2005) Influence of GSTM1, GSTT1, GSTP1 and NAT2 genotypes on the p53 mutational spectrum in bladder tumours. Int J Cancer 113(5):761–768

    Article  PubMed  CAS  Google Scholar 

  32. Salagovic J, Kalina I, Stubna J, Habalova V, Hrivnak M, Valansky L, Kohut A, Biros E (1998) Genetic polymorphism of glutathione S-transferase M1 and T1 as a risk factor in lung and bladder cancers. Neoplasma 45:312–317

    PubMed  CAS  Google Scholar 

  33. McGrath M, Michaud D, De Vivo L (2006) Polymorphisms in GSTT1, GSTM1, NAT1 and NAT2 genes and bladder cancer risk in men and women. BMC Cancer 6:239

    Article  PubMed  CAS  Google Scholar 

  34. Lin JH, Lu AY (1998) Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet 35(5):361–390

    Article  PubMed  CAS  Google Scholar 

  35. Kellen E, Zeegers M, Paulussen A, Vlietinck R, Vlem EV, Veulemans H, Buntinx F (2007) Does occupational exposure to PAHs, diesel and aromatic amines interact with smoking and metabolic genetic polymorphisms to increase the risk on bladder cancer? The Belgian case control study on bladder cancer risk. Cancer Lett 245(1–2):51–60

    Article  PubMed  CAS  Google Scholar 

  36. Brockmöller J, Cascorbi I, Kerb R, Roots I (1996) Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk. Cancer Res 56:3915–3925

    PubMed  Google Scholar 

  37. Katoh T (1995) Application of molecular biology to occupational health field—the frequency of gene polymorphism of cytochrome P450 1A1 and glutathione S-transferase M1 in patients with lung, oral and urothelial cancer. J UOEH 17(4):271–278

    PubMed  CAS  Google Scholar 

  38. Daly AK, Thomas DJ, Cooper J, Pearson WR, Neal DE, Idle JR (1993) Homozygous deletion of gene for glutathione S-transferase M1 in bladder cancer. BMJ 307(6902):481–482

    Article  PubMed  CAS  Google Scholar 

  39. Mungan NA, Aben KKH, Beeks E, Kampman E, Bunschoten A, Bussemakers M, Witjes JA, Kiemeney LALM (2000) A germline homozygote deletion of the glutathione-S-transferase Mu1 gene predisposes to bladder cancer. Urol Int 64:134–138

    Article  PubMed  CAS  Google Scholar 

  40. Arruda VR, Grignolli CE, Goncalves MS, Soares MC, Menezes R, Saad ST, Costa FF (1998) Prevalence of homozygosity for the deleted alleles of glutathione S-transferase mu (GSTM1) and theta (GSTT1) among distinct ethnic groups from Brazil: relevance to environmental carcinogenesis? Clin Genet 54(3):210–214

    PubMed  CAS  Google Scholar 

  41. Parra FC, Amado RC, Lambertucci JR, Rocha J, Antunes MC, Pena SDJ (2003) Color and genomic ancestry in Brazilians. Proc Natl Acad Sci USA 100:177–182

    Article  PubMed  CAS  Google Scholar 

  42. Brescia G, Celotti L, Clonfero E, Neumann HG, Forni A, Foà V, Pisoni M, Ferri GM, Assennato G (1999) The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers. J Arch Toxicol 73:8–9 431–439

    Google Scholar 

  43. Agundez JA (2004) Cytochrome P450 gene polymorphism and cancer. Curr Drug Metab 5:211–224

    Article  PubMed  CAS  Google Scholar 

  44. Katoh T, Inatomi H, Nagaoka A, Sugita A (1995) Cytochrome P4501A1 gene polymorphism and homozygous deletion of the glutathione S-transferase M1 gene in urothelial cancer patients. Carcinogenesis 16:655–657

    Article  PubMed  CAS  Google Scholar 

  45. Houlston RS, Johns LE (2000) Glutathione S-transferase mu1 (GSTM1) status and bladder cancer risk: a meta-analysis. Mutagenesis 15(5):399–404

    Article  PubMed  Google Scholar 

  46. Nair U, Bartsch H (2001) Metabolic polymorphisms as susceptibility markers for lung and oral cavity cancer. IARC Sci Publ 154:271–290

    PubMed  CAS  Google Scholar 

  47. Quinones L, Lucas D, Godoy J, Caceres D, Berthou F, Varela N, Lee K, Acevedo C, Martinez L, Aguilera AM, Gil L (2001) CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people. Cancer Lett 174:35–44

    Article  PubMed  CAS  Google Scholar 

  48. Kim EJ, Jeong P, Quan C, Kim J, Bae SC, Yoon SJ, Kang JW, Lee SC, Jun Wee J, Kim WJ (2005) Genotypes of TNF-alpha, VEGF, hOGG1, GSTM1, and GSTT1: useful determinants for clinical outcome of bladder cancer. Urology 65(1):70–75

    Article  PubMed  Google Scholar 

  49. Brockmöller J, Kaiser R, Kerb R, Cascorbi I, Jaeger V, Roots I (1996) Polymorphic enzymes of xenobiotic metabolism as modulators of acquired P53 mutations in bladder cancer. Pharmacogenetics 6:535–545

    Article  PubMed  Google Scholar 

  50. Carstensen U, Alexandrie AK, Hogstedt B, Rannug A, Bratt I, Hagmar L (1993) B- and T-lymphocyte micronuclei in chimney sweeps with respect to genetic polymorphism for CYP1A1 and GST1 (class Mu). Mutat Res 289(2):187–195

    PubMed  CAS  Google Scholar 

  51. Sobti RC, Al-Badran AI, Sharma S, Sharma SK, Krishan A, Mohan H (2005) Genetic polymorphisms of CYP2D6, GSTM1, and GSTT1 genes and bladder cancer risk in North India. Cancer Genet Cytogenet 156(1):68–73

    Article  PubMed  CAS  Google Scholar 

  52. Sanyal S, Festa F, Sakano S, Zhang Z, Steineck G, Norming U, Wijkstrom H, Larsson P, Kumar R, Hemminki K (2004) Polymorphisms in DNA repair and metabolic genes in bladder cancer. Carcinogenesis 25(5):729–734

    Article  PubMed  CAS  Google Scholar 

  53. Naccarati A, Soucek P, Stetina R, Haufroid V, Kumar R, Vodickova L, Trtkova K, Dusinska M, Hemminki K, Vodicka P (2006) Genetic polymorphisms and possible gene-gene interactions in metabolic and DNA repair genes: effects on DNA damage. Mutat Res 593(1–2):22–31

    PubMed  CAS  Google Scholar 

  54. Dörrenhaus A, Müller T, Roos PH (2007) Increased CYP1A1 expression in human exfoliated urothelial cells of cigarette smokers compared to non-smokers. Arch Toxicol 81:19–25

    Article  PubMed  CAS  Google Scholar 

  55. Roos PH, Belik R, Föllmann W, Degen GH, Knopf HJ, Bolt HM, Golka K (2006) Expression of cytochrome P450 enzymes CYP1A1, CYP1B1, CYP2E1 and CYP4B1 in cultured transitional cells from specimens of the human urinary tract and from urinary sediments. Arch Toxicol 80:45–52

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank the Londrina Cancer Institute (ICL) for sample collection. The authors would like to thank the Universidade Estadual de Londrina and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Proap) for the financial support of the work and for fellowship to Grando, J. P. S.; the Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq) for fellowship to Kuasne, H. and grant awarded to Cólus, I. M. S.

Conflict of interest statement

All the authors of the manuscript entitled “Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer” declare to have no conflict of interest related to the publication of this manuscript.

Author information

Authors and Affiliations

  1. Departamento de Biologia Geral, CCB, Universidade Estadual de Londrina, Londrina, PR, Brazil

    Hellen Kuasne, Roberta Losi-Guembarovski, Iara Sant’Ana Rodrigues, Henrique Mitsu Matsuda, Rodrigo Paes de Menezes & Ilce Mara de Syllos Cólus

  2. Hospital do Câncer de Londrina, Londrina, PR, Brazil

    João Paulo Souto Grando, Paulo Emílio Fuganti, Émerson Pereira Gregório & Farid Libos Júnior

  3. Departamento de Cirurgia, CCS, Universidade Estadual de Londrina, Londrina, PR, Brazil

    João Paulo Souto Grando & Marco Aurélio de Freitas Rodrigues

Authors
  1. João Paulo Souto Grando
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hellen Kuasne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberta Losi-Guembarovski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Iara Sant’Ana Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henrique Mitsu Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paulo Emílio Fuganti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Émerson Pereira Gregório
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Farid Libos Júnior
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rodrigo Paes de Menezes
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marco Aurélio de Freitas Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ilce Mara de Syllos Cólus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ilce Mara de Syllos Cólus.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grando, J.P.S., Kuasne, H., Losi-Guembarovski, R. et al. Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer. Clin Exp Med 9, 21–28 (2009). https://doi.org/10.1007/s10238-008-0015-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-008-0015-z

Keywords

Search

Navigation