Advertisement

Molecular Biology Reports

, Volume 37, Issue 1, pp 263–267 | Cite as

Investigation of glutathione S-transferase M1 and T1 deletions in lung cancer

  • Julide Altinisik
  • Zinnet B. Balta
  • Gunay Aydin
  • Turgut Ulutin
  • Nur Buyru
Article

Abstract

Glutathione S-transferases (GSTs) M1 and T1 are known to be polymorphic in humans. Both polymorphisms are due to gene deletions which are responsible for the existence of null genotypes. Previous studies have suggested that GST genotypes may play a role in determining susceptibility to a number of unrelated cancers, including lung cancer. The GSTM1 and GSTT1 polymorphisms were determined by PCR-based analysis in 75 lung cancer patients and 55 controls. The unconditional logistic regression analysis was used to calculate ORs and 95% CI. The frequencies of GSTM1 and GSTT1 null genotypes were 37.3 and 22.7% in lung cancer patients and 27.3 and 16.4% in controls, respectively. When analyzed by histology the GSTM1 null genotype was more prevalent in squamous-cell carcinoma and adenocarcinoma patients. Whereas, GSTT1 null genotype frequency was lower in small-cell lung cancer patients than controls. But these differences were not statistically significant. According to smoking status, null genotype for both gene are associated with an increase in risk for lung cancer. Our results suggest that GSTM1 and GSTT1 polymorphisms may play a role in the development of lung cancer for some histological subtypes and modifies the risk of smoking-related lung cancer.

Keywords

GSTM1 GSTT1 Gene polymorphism Lung cancer 

Notes

Acknowledgments

This work was supported by the Research Fund of the University of Istanbul. Project number: 251/23082004

References

  1. 1.
    Sqita MR, Wei Q, Li G, Wu X (1999) Genetic susceptibility to tobacco carcinogenesis. Cancer Invest 17:661–662CrossRefGoogle Scholar
  2. 2.
    Pelkonen O, Nebert DW (1982) Metabolism of polycyclic aromatic hydrocarbons: etiologic role in carcinogenesis. Pharmacol Rev 34:189–222PubMedGoogle Scholar
  3. 3.
    Mannervik B, Danielson UH (1988) Glutathione transferases structure and catalytic activity. CRC Crit Rev Biochem 23:283–337CrossRefPubMedGoogle Scholar
  4. 4.
    Harris CC (1986) Tobacco smoke and lung disease: who is susceptible? Ann Intern Med 5:607–609Google Scholar
  5. 5.
    Seidegard J, Pero RW (1985) The hereditary transmission of high glutathione transferase activity toward transtilbene oxide in human mononuclear leukocytes. Hum Genet 69:66–68CrossRefPubMedGoogle Scholar
  6. 6.
    Pemble S, Schröder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB (1994) Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300:271–276PubMedGoogle Scholar
  7. 7.
    Kliencke JK, Kelsey KT, Lamela RA, Toscano WA (1990) Human glutathione S-transferase deficiency as a marker of susceptibility to epoxide-induced cytogenetic damage. Cancer Res 50:1585–1590Google Scholar
  8. 8.
    Seidegard J, Pero RW, Miller DG, Beattie EJ (1986) A glutathione transferase in human leukocytes as a marker fort he susceptibility to lung cancer. Carcinogenesis 7:751–753. doi: 10.1093/carcin/7.5.751 CrossRefPubMedGoogle Scholar
  9. 9.
    Bell DA, Taylor JA, Paulson DF, Robertson CN, Mohler JL, Lucier GW (1993) Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen metabolism gene glutathione-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst 85:1159–1164. doi: 10.1093/jnci/85.14.1159 CrossRefPubMedGoogle Scholar
  10. 10.
    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 16:1655–1657. doi: 10.1093/carcin/16.7.1655 CrossRefPubMedGoogle Scholar
  11. 11.
    Zhong S, Wyllre AH, Barnes D, Wolf CR, Spurr NK (1993) Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14:1821–1824. doi: 10.1093/carcin/14.9.1821 CrossRefPubMedGoogle Scholar
  12. 12.
    Hengstler JG, Arand M, Herrero ME, Oesch F (1998) Recent results cancer research: polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. In: Schwab M (ed) Genes and environment. Springer, New York, pp 47–85Google Scholar
  13. 13.
    Meyer DJ, Coles B, Pemble SE, Gilmore KS, Fraser GM, Ketterer B (1991) Theta, a new class of glutathione-transferases purified from rat and man. Biochem J 274:409–414PubMedGoogle Scholar
  14. 14.
    Schroeder KR, Hallier E, Peter H, Bolt HM (1992) Dissociation of a new glutathione S-transferase in human erythrocytes. Biochem Pharmacol 43:1671–1674CrossRefGoogle Scholar
  15. 15.
    Hussey AJ, Hayes JD (1992) Characterization of a human class-theta glutathione S-transferase with activity towards 1-menaphthyl sulphate. Biochem J 286:926–935Google Scholar
  16. 16.
    Tan KL, Webb GC, Baker RT, Board PG (1995) Molecular cloning of a cDNA and chromosomal localisation of a human theta-class glutathione S-transferase gene (GSTT2–2) to chromosome 22. Genomics 25:381–387CrossRefPubMedGoogle Scholar
  17. 17.
    Hallier E, Schröder KR, Asmuth K, Dommermuth A, Aust B, Goergens HW (1994) Metabolism of dichloromethanemethylchloride to formaldehydein human erythrocytes: influence of polymorphism of glutathione transferase theta (GSTT1-1). Arch Toxicol 68:423–427CrossRefPubMedGoogle Scholar
  18. 18.
    Lee EJ, Wong JY, Yeoh PN, Gong NH (1995) Glutathione S-transferase theta (GST1) genetic polymorphism among Chinese, Malays and Indians in Singapore. Pharmacogenetics 5:332–334CrossRefPubMedGoogle Scholar
  19. 19.
    Nelson HH, Wiencke JK, Christiani DC, Cheng TJ, Zuo ZF, Schwartz BS, Lee BK, Spitz MR, Wang M, Xu X (1995) Ethnic differences in the prevalence of the homozygously deleted genotype of glutathione S-transferase theta. Carcinogenesis 16:1243–1245CrossRefPubMedGoogle Scholar
  20. 20.
    Chen H, Sandler DP, Taylor JA, Shore DL, Liu E, Bloomfield CD, Bell DA (1996) Increased risk for myelodysplastic syndromes in individuals with glutathione transferase θ 1 (GSTT1) gene defect. Lancet 347:295–297CrossRefPubMedGoogle Scholar
  21. 21.
    Elexpuru-Camiruaga J, Buxton N, Kandula V, Dias PS, Campbell D, McIntosh J, Broome J, Jones P, Inskip A, Alldersea J (1995) Susceptibility to astrocytoma and meningioma: influence of allelism at glutathione S-transferase (GSTT1 and GSTM1) and cytochrome p-450 (CYP2D6) loci. Cancer Res 55:4237–4239PubMedGoogle Scholar
  22. 22.
    Jourenkova-Mironova N, Wikman H, Bouchardy C, Voho A, Dayer P, Benhamou S, Hirvonen A (1998) Role of glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes in modulating susceptibility to smoking-related lung cancer. Pharmacogenetics 8:495–502CrossRefPubMedGoogle Scholar
  23. 23.
    Kihara M, Noda K (1999) Lung cancer risk of the GSTM1 null genotype is enhanced in the presence of the GSTP1 mutated genotype in male Japanese smokers. Cancer Lett 137:53–60CrossRefPubMedGoogle Scholar
  24. 24.
    Wang J, Deng Y, Cheng J, Ding J, Tokudome S (2003) GST genetic polymorphisms and lung adenocarcinoma susceptibility in a Chinese population. Cancer Lett 201:185–193. doi: 10.1016/S0304-3835(03)00480-4 CrossRefPubMedGoogle Scholar
  25. 25.
    Hayes JD, Strange RC (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61:154–166. doi: 10.1159/000028396 CrossRefPubMedGoogle Scholar
  26. 26.
    Belogubova EV, Togo AV, Karpova MB, Kuligina E, Buslov KG, Ulibina JM, Lemehov VG, Romanenko SM, Shutkin VA, Hanson KP, Hirvonen A, Imyanitov EN (2004) A novel approach for assessment of cancer predisposing roles of GSTM1 and GSTT1 genes: use of putatively cancer resistant elderly tumor-free smokers as the referents. Lung Cancer 43:259–266. doi: 10.1016/j.lungcan.2003.08.019 CrossRefPubMedGoogle Scholar
  27. 27.
    Houlston RS (1999) Glutathione S-transferase M1 status and lung cancer risk: a meta analysis. Cancer Epidemiol Biomarkers Prev 8:675–682PubMedGoogle Scholar
  28. 28.
    Nazar-Stewart V, Vaughan TL, Stapleton P, VanLoo J, Nicol-Blades B, Eaton DL (2003) A population-based study of glutathione S-transferase M1, T1 and P1 genotypes and risk for lung cancer. Lung Cancer 40:247–258. doi: 10.1016/S0169-5002(03)00076-X PubMedGoogle Scholar
  29. 29.
    Chan-Yeung M, Tan-Un KC, Ip MSM, Tsang KWT, Ho SP, Ho JCM, Chan H, Lam WK (2004) Lung cancer susceptibility and polymorphisms of glutathione S-transferase genes in Hong Kong. Lung Cancer 45:155–160. doi: 10.1016/j.lungcan.2004.01.016 CrossRefPubMedGoogle Scholar
  30. 30.
    Raimondi S (2005) Metabolic gene polymorphisms and lung cancer risk in non-smakers. An update of the GSEC study. Mutat Res 592:45–57. doi: 10.1016/j.mrfmmm.2005.06.002 PubMedGoogle Scholar
  31. 31.
    Schneider J, Bernges U, Philipp M, Woitowitz HJ (2004) GSTM1, GSTT1 and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking. Cancer Lett 208:65–74. doi: 10.1016/j.canlet.2004.01.002 CrossRefPubMedGoogle Scholar
  32. 32.
    Benhamou S, Lee WJ, Alexandrie AK, Boffetta P, Bouchardy C, Butkiewicz D, Brockmöller J, Clapper ML, Daly A, Dolzan V, Ford J, Gaspari L, Haugen A, Hirvonen A, Husgafvel-Pursiainen K, Ingelman-Sundberg M, Kalina I, Kihara M, Kremers P, Le Marchand L, London SJ, Nazar-Stewart V, Ono-Kihara M, Rannug A, Romkes M, Ryberg D, Seidegard J, Shields P, Strange RC, Stücker I, To-Figueras J, Brennan P, Taioli E (2002) Meta- and pooled analysis of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk. Carcinogenesis 23:1343–1350. doi: 10.1093/carcin/23.8.1343 CrossRefPubMedGoogle Scholar
  33. 33.
    Lewis SJ, Cherry NM, Niven RML, Barber PV, Povey AC (2002) GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk. Cancer Lett 180:165–171. doi: S0304-3835(02)00028-9 CrossRefPubMedGoogle Scholar
  34. 34.
    Ford JG, Li Y, O’Sullivan MM, Demopoulos R, Garte S, Taioli E, Brandt-Rauf PW (2000) Glutathione S-transferase M1 polymorphism and lung cancer risk in African-Americans. Carcinogenesis 21:1971–1975. doi: 10.1093/carcin/21.11.1971 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Julide Altinisik
    • 1
  • Zinnet B. Balta
    • 2
  • Gunay Aydin
    • 2
  • Turgut Ulutin
    • 1
  • Nur Buyru
    • 1
  1. 1.Cerrahpasa Medical Faculty, Department of Medical BiologyIstanbul UniversityKocamustafapasa, IstanbulTurkey
  2. 2.Cerrahpasa Medical Faculty, Department of PneumologyIstanbul UniversityIstanbulTurkey

Personalised recommendations