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Table of Contents
Vol. 61, No. 3, 2000
Issue release date: September 2000
Pharmacology 2000;61:154–166
(DOI:10.1159/000028396)

Glutathione S-Transferase Polymorphisms and Their Biological Consequences

Hayes J.D. · Strange R.C.
aBiomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, and bCentre for Cell and Molecular Medicine, School of Postgraduate Medicine, Keele University, North Staffordshire Hospital, Stoke-on-Trent, UK

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Abstract

Two supergene families encode proteins with glutathione S-transferase (GST) activity: the family of soluble enzymes comprises at least 16 genes; the separate family of microsomal enzymes comprises at least 6 genes. These two GST families are believed to exert a critical role in cellular protection against oxidative stress and toxic foreign chemicals. They detoxify a variety of electrophilic compounds, including oxidized lipid, DNA and catechol products generated by reactive oxygen species-induced damage to intracellular molecules. An increasing number of GST genes are being recognized as polymorphic. Certain alleles, particularly those that confer impaired catalytic activity (e.g. GSTM1*0, GSTT1*0), may be associated with increased sensitivity to toxic compounds. GST polymorphisms may be disease modifying; for example, in subgroups of patients with basal cell carcinoma or bronchial hyper-responsiveness, certain GST appear to exert a statistically significant and biologically relevant impact on disease susceptibility.

Copyright © 2000 S. Karger AG, Basel



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References

  1. Klaassen CD: Casarett and Doull’s Toxicology. The Basic Science of Poisons, ed 5. New York, McGraw-Hill, 1996.
  2. Hayes JD, McLellan LI: Glatathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Rad Res 1999;31:273–300.
  3. Hayes JD, Wolf CR: Molecular mechanisms of drug resistance. Biochem J 1990;272:281–295.
  4. Albert A: Selective Toxicity. The Physico-Chemical Basis of Therapy, ed 7. London, Chapman & Hall, 1985.
  5. Smith G, Stanley LA, Sim E, Strange RC, Wolf CR: Metabolic polymorphisms and cancer susceptibility. Cancer Surv 1995;25:27–65.
  6. Seidegård J, Ekström G: The role of human glutathione transferases and epoxide hydrolases in the metabolism of xenobiotics. Envir Health Perspect 1997;105(suppl 4):791–799.
  7. Autrup H: Genetic polymorphisms in human xenobiotica metabolizing enzymes as susceptibility factors in toxic response. Mutation Res 2000;464:65–76.
  8. Hayes JD, Strange RC: Potential contribution of the glutathione S-transferase supergene family to resistance to oxidative stress. Free Rad Res 1995;22:193–207.
  9. Hayes JD, Pulford DJ: 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 1995;30:445–600.
  10. Mannervik B, Wildersten M: Human glutathione transferases: classification, tissue distribution, structure, and functional properties; in Pacifici GM, Fracchia GN (eds): Advances in Drug Metabolism in Man. European Commission, 1995, pp 407–459.
  11. Whalen R, Boyer TD: Human glutathione S-transferases. Semin Liver Dis 1998;18:345–358.
  12. Jakobsson P-J, Morgenstern R, Mancini J, Ford-Hutchinson A, Persson B: Common structural features of MAPEG – a widespread superfamily of membrane associated proteins with highly divergent functions in eicosanoid and glutathione metabolism. Protein Sci 1999;8:689–692.
  13. Jakobsson P-J, Thorén S, Morgenstern R, Samuelsson B: Identification of human prostaglandin E synthase: A microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci USA 1999;96:7220–7225. 13 (a) Forsberg L, Leeb L, Thorén S, Morgenstern R, Jakobsson P-J: Human glutathione dependent prostaglandin E synthase: Gene structure and regulation. FEBS Lett 2000;471:78–82.
  14. Pemble SE, Wardle AF, Taylor JB: Glutathione S-transferase class kappa: Characterization by the cloning of rat mitochondrial GST and identification of a human homologue. Biochem J 1996;319:749–754.
  15. Booth J, Boyland E, Sims P: An enzyme from rat liver catalysing conjugations with glutathione. Biochem J 1961;79:516–524.
  16. Coombes B, Stakelum GS: A liver enzyme that conjugates sulfobromophthalein with glutathione. J Clin Invest 1961;40:981–988.
  17. Clark AG, Smith JN, Speirs TW: Cross specificity in some vertebrate and insect glutathione S-transferases with methyl parathion (dimethyl p-nitrophenyl phosphorothionate), 1-chloro-2,4-dinitrobenzene and s-crotonyl-N-acetylcysteamine as substrates. Biochem J 1973;135:385–392.

    External Resources

  18. Mannervik B: The isoenzymes of glutathione transferase. Adv Enzymol Rel Areas Mol Biol 1985;57:357–417.
  19. Rowe JD, Nieves E, Listowsky I: Subunit diversity and tissue distribution of human glutathione S-transferases: Intepretations based on electrospray ionization-MS and peptide sequence-specific antisera. Biochem J 1997;325:481–486.

    External Resources

  20. Sherratt PJ, Pulford DJ, Harrison DJ, Green T, Hayes JD: Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse. Comparison of the tissue distribution of GSTT1-1 with that of classes Alpha, Mu and Pi GST in human. Biochem J 1997;326:837–846.

    External Resources

  21. Jakobsson P-J, Mancini JA, Ford-Hutchinson AW: Identification and characterization of a novel human microsomal glutathione S-transferase with leukotriene C4 synthase activity and significant sequence identity to 5-lipoxygenase-activating protein and leukotriene C4 synthase. J Biol Chem 1996;271:22203–22210.
  22. Scoggan KA, Jakobsson P-J, Ford-Hutchinson AW: Production of leukotriene C4 in different human tissues is attributable to distinct membrane bound biosynthetic enzymes. J Biol Chem 1997;272:10182–10187.
  23. Jakobsson P-J, Mancini JA, Riendeau D, Ford-Hutchinson AW: Identification and characterization of a novel microsomal enzyme with glutathione-dependent transferase and peroxidase activities. J Biol Chem 1997;272:22934–22939.
  24. Estonius M, Forsberg L, Danielsson O, Weinander R, Kelner MJ, Morgenstern R: Distribution of microsomal glutathione transferase 1 in mammalian tissues: A predominant alternate first exon in human tissues. Eur J Biochem 1999;260:409–413. 24 (a) Kelner J, Bagnell RD, Montoya MA, Estes LA, Forsberg L, Morgenstern R: Structural organization of the microsomal glutathione S-transferase gene (MGST1) on chromosome 12p13.1-13.2. Identification of the correct promoter region and demonstration of transcriptional regulation in response to oxidative stress. J Biol Chem 2000;275:13000–13006.
  25. Lee SH, DeJong J: Microsomal GST-I: Genomic organization, expression, and alternative splicing of the human gene. Biochim Biophys Acta 1999;1446:389–396.
  26. Ricci G, Caccuri AM, Lo Bello M, Pastore A, Piemonte F, Federici G: Colorimetric and fluorometric assays of glutathione transferase based on 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. Anal Biochem 1994;218:463–465.
  27. Burgess JR, Chow N-WI, Reddy CC, Tu C-PD: Amino acid substitutions in the human glutathione S-transferases confer different specificities in the prostaglandin endoperoxide conversion pathway. Biochem Biophys Res Commun 1989;158:497–502.
  28. Hubatsch I, Ridderström M, Mannervik B: Human glutathione transferase A4-4: An Alpha class enzyme with high catalytic efficiency in the conjugation of 4-hydroxynonenal and other genotoxic products of lipid peroxidation. Biochem J 1998;330:175–179.
  29. Board PG: Identification of cDNAs encoding two human Alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4. Biochem J 1998;330:827–831.
  30. Liu S, Stoesz SP, Pickett CB: Identification of a novel human glutathione S-transferase using bioinformatics. Arch Biochem Biophys 1998;352:306–313.
  31. Berhane K, Widersten M, Engström Å, Kozarich JW, Mannervik B: Detoxication of base propenals and other α,β-unsaturated aldehyde products of radical reactions and lipid peroxidation by human glutathione transferases. Proc Natl Acad Sci USA 1994;91:1480–1484.

    External Resources

  32. Comstock KE, Widersten M, Hao X-Y, Henner WD, Mannervik B: A comparison of the enzymatic and physicochemical properties of human glutathione transferase M4-4 and three other human class Mu enzymes. Arch Biochem Biophys 1994;311:487–495.
  33. Baez S, Segura-Aguilar J, Widersten M, Johansson A-S, Mannervik B: Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes. Biochem J 1997;324:25–28.
  34. Patskovsky YV, Patskovska LN, Listowsky I: Functions of His 107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a. Biochemistry 1999;38:1193–1202.

    External Resources

  35. Patskovsky YV, Patskovska LN, Listowsky I: The enhanced affinity for thiolate anion and activation of enzyme-bound glutathione is governed by an arginine residue of human Mu class glutathione S-transferases. J Biol Chem 2000;275:3296–3304. 35 (a) Kanaoka Y, Fujimori K, Kikuno R, Sakaguchi Y, Urade Y, Hayaishi O: Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase. Conservation of the ancestral genomic structure of sigma-class glutathione S-transferase. Eur J Biochem 2000;267:3315–3322.
  36. Board PG, Baker RT, Chelvanayagam G, Jermiin LS: Zeta, a novel class of glutathione transferases in a range of species from plants to humans. Biochem J 1997;328:929–935.

    External Resources

  37. Tong Z, Board PG, Anders MW: Glutathione transferase Zeta catalyses the oxygenation of the carcinogen dichloroacetic acid to glyoxylic acid. Biochem J 1998;331:371–374.

    External Resources

  38. Tong Z, Board PG, Anders MW: Glutathione transferase Zeta-catalyzed biotransformation of dichloroacetic acid and other α-haloacids. Chem Res Toxicol 1998;11:1332–1338.
  39. Tzeng H-F, Blackburn A, Board PG, Anders MW: Selective inactivation of polymorphic variants of glutathione transferase Zeta by dichloroacetate. ISSX abstract, 1999.
  40. Retief JD, Lynch KR, Pearson WR: Panning for genes – a visual strategy for identifying novel gene orthologs and paralogs. Genome Res 1999;9:373–382. 40 (a) Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, Danley DE, Hoth LR, Griffor MC, Komath AV, Rosner MH, Chrunyk BA, Perregaux DE, Gabel CA, Geoghegan KF, Pandit J: Identification, characterization and chrystal structure of the Omega class glutathione transferases. J Biol Chem 2000;275:24798–24806.
  41. Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B: A model for p53-induced apoptosis. Nature 1997;389:300–305.
  42. Johnson WW, Ueng Y-F, Widersten M, Mannervik B, Hayes JD, Sherratt PJ, Ketterer B, Guengerich FP: Conjugation of highly reactive aflatoxin B1 exo-8,9-epoxide catalysed by rat and human glutathione transferases: Estimation of kinetic parameters. Biochemistry 1997;36:3056–3060.

    External Resources

  43. Hu X, Ji X, Srivastava SK, Xia H, Awasthi S, Nanduri B, Awasthi YC, Zimniak P, Singh SV: Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1-1 in the glutathione conjugation of carcinogenic diol epoxides of chrysene. Arch Biochem Biophys 1997;345:32–38.

    External Resources

  44. Hu X, Xia H, Srivastava SK, Pal A, Awasthi YC, Zimniak P, Singh SV: Catalytic efficiencies of allelic variants of human glutathione S-transferase P1-1 toward carcinogenic anti-diol epoxides of benzo[c]phenanthrene and benzo[g]chrysene. Cancer Res 1998;58:5340–5343.
  45. Hu X, O’Donnell R, Srivastava SK, Xia H, Zimniak P, Nanduri B, Bleicher RJ, Awasthi S, Awasthi YC, Ji X, Singh SV: Active site architecture of polymorphic forms of human glutathione S-transferase P1-1 accounts for their enantioselectivity and disparate activity in the glutathione conjugation of 7β,8α-dihydroxy-9α,10α-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Biochem Biophys Res Commun 1997;235:424–428.

    External Resources

  46. Hu X, Xia H, Srivastava SK, Herzog C, Awasthi YC, Ji X, Zimniak P, Singh SV: Activity of four allelic forms of glutathione S-transferase hGSTP1-1 for diol epoxides of polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun 1997;238:397–402.

    External Resources

  47. Listowsky I, Abramovitz M, Homma H, Niitsu Y: Intracellular binding and transport of hormones and xenobiotics by glutathione S-transferase. Drug Metab Rev 1988;19:305–318.

    External Resources

  48. Urade Y, Watanabe K, Hayaishi O: Prostaglandin D, E, and F synthases. J Lipid Mediators Cell Signalling 1995;12:257–273.

    External Resources

  49. Reginato MJ, Krakow SL, Bailey ST, Lazar MA: Prostaglandins promote and block adipogenesis through opposing effects on peroxisome proliferator-activated receptor γ. J Biol Chem 1998;273:1855–1858.
  50. Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG: Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 2000;403:103–108.
  51. Bogaards JJP, Venekamp JC, van Bladeren PJ: Stereoselective conjugation of prostaglandin A2 and prostaglandin J2 with glutathione, catalysed by the human glutathione S-transferases A1-1, A2-2. M1a-1a, and P1-1. Chem Res Toxicol 1997;10:310–317.
  52. Plummer SM, Holloway KA, Manson MM, Munks RJL, Kaptein A, Farrow S, Howells L: Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex. Oncogene 1999;18:6013–6021.

    External Resources

  53. Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM: 15-Deoxy-Δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell 1995;83:803–812.
  54. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK: The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 1998;391:79–82.
  55. Adams M, Reginato MJ, Shao D, Lazar MA, Chatterjee VK: Transcriptional activation by peroxisome proliferator-activated receptor γ is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site. J Biol Chem 1997;272:5128–5132.
  56. Camp HS, Tafuri SR: Regulation of peroxisome proliferator-activated receptor γ activity by mitogen-activated protein kinase. J Biol Chem 1997;272:10811–10816.
  57. Adler V, Yin Z, Fuchs SY, Benezra M, Rosario L, Tew KD, Pincus MR, Sardana M, Henderson CJ, Wolf CR, Davis RJ, Ronai Z: Regulation of JNK signaling by GSTp. EMBO J 1999;18:1321–1334. 57 (a) Bernardini S, Bernassola F, Cortese C, Ballerini S, Melino G, Motti C, Bellincampi L, Iori R, Federici G: Modulation of GST P1-1 activity by polymerization during apoptosis. J Cell Biochem 2000;77:645–653.
  58. Scott EM, Wright RC: Variability of glutathione S-transferase of human erythrocytes. Am J Hum Genet 1980;32:115–117.

    External Resources

  59. Warholm M, Guthenberg C, Mannervik B, von Bahr C, Glaumann H: Identification of a new glutathione S-transferase in human liver. Acta Chem Scand 1980;B34:607–610.
  60. Board PG: Biochemical genetics of glutathione S-transferases in man. Am J Hum Genet 1981;33:36–43.
  61. Board PG: Gene deletion and partial deficiency of the glutathione S-transferase (ligandin) system in man. FEBS Lett 1981;135:12–14.
  62. Seidegård J, Pero RW: The hereditary transmission of high glutathione transferase activity towards trans-stilbene oxide in human mononuclear leukocytes. Hum Genet 1985;69:66–68.

    External Resources

  63. Hussey AJ, Hayes JD, Beckett GJ: The polymorphic expression of neutral glutathione S-transferases in human mononuclear leukocytes as measured by specific radioimmunoassay. Biochem Pharmacol 1987;36:4013–4015.
  64. Juronen E, Tasa G, Uusküla M, Pooga M, Mikelsaar A-V: Production and characterization of monoclonal antibodies against class Theta glutathione S-transferase T1-1. Hybridoma 1996;15:77–82.

    External Resources

  65. Forsberg L, de Faire U, Morgenstern R: Low yield of polymorphisms from EST blast searching: Analysis of genes related to oxidative stress and verification of the P197L polymorphism in GPX1. Human Mut 1999;13:294–300. 65 (a) Forsberg L: Genetic variation and regulation of oxidative stress related genes. PhD Thesis 2000; Karolinska Institutet, University of Stockholm, Sweden.
  66. Blackburn AC, Tzeng H-F, Anders MW, Board PG: Discovery of a functional polymorphism in human glutathione transferase Zeta by expressed sequence tag database analysis. Pharmacogenetics 2000;10:49–57.
  67. Rhoads DM, Zarlengo RP, Tu C-PD: The basic glutathione S-transferases from human livers are products of separate genes. Biochem Biophys Res Commun 1987;145:474–481.
  68. Chen LZ, Board PG: Hgi AI restriction fragment length polymorphism at the human glutathione S-transferase 2 locus. Nucl Acids Res 1987;15:6306.

    External Resources

  69. Hayes JD, Kerr LA, Cronshaw AD: Evidence that glutathione S-transferases B1B1 and B2B2 are the products of separate genes and that their expression in human liver is subject to inter-individual variation. Molecular relationships between the B1 and B2 subunits and other Alpha class glutathione S-transferases. Biochem J 1989;264:437–445.

    External Resources

  70. Röhrdanz E, Nguyen T, Pickett CB: Isolation and characterization of the human glutathione S-transferase A2 subunit gene. Arch Biochem Biophys 1992;298:747–752.

    External Resources

  71. Seidegård J, De Pierre JW, Pero RW: Hereditary interindividual differences in the glutathione transferase activity towards trans-stilbene oxide in resting human mononuclear leukocytes are due to a particular isozyme(s). Carcinogenesis 1985;6:1211–1216.

    External Resources

  72. Widersten M, Pearson WR, Engström Å, Mannervik B: Heterologous expression of the allelic variant Mu-class glutathione transferases μ and ψ. Biochem J 1991;276:519–524.

    External Resources

  73. Seidegård J, Vorachek WR, Pero RW, Pearson WR: Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion. Proc Natl Acad Sci USA 1988;85:7293–7297.
  74. Xu S, Wang Y, Pearson WR: Characterization of the human class Mu glutathione S-transferase gene cluster and the GSTM1 deletion. J Biol Chem 1998;273:3517–3527.
  75. McLellan RA, Oscarson M, Alexandrie A-K, Seidegård J, Price Evans DA, Rannug A, Ingelman-Sundberg M: Characterization of a human glutathione S-transferase μ cluster containing a duplicated GSTM1 gene that causes ultrarapid enzyme activity. Mol Pharmacol 1997;52:958–965.

    External Resources

  76. Inskip A, Elexperu-Camiruaga J, Buxton N, Dias PS, MacIntosh J, Campbell D, Jones PW, Yengi L, Talbot JA, Strange RC, Fryer AA: Identification of polymorphism at the glutathione S-transferase, GSTM3 locus: evidence for linkage with GSTM1*A. Biochem J 1995;312:713–716. 76 (a) Emahazion YV, Jobs M, Howell WM, Siegfried M, Wyöni P-I, Prince JA, Brookes AJ: Identification of 167 polymorphisms in 88 genes from candidate neurodegeneration pathways. Gene 1999;238:315–324.

    External Resources

  77. Patskovsky YV, Huang M-Q, Takayama T, Listowsky I, Pearson WR: Distinctive structure of the human GSTM3 gene-inverted orientation relative to the Mu class glutathione transferase gene cluster. Arch Biochem Biophys 1999;361:85–93.
  78. Ali-Osman F, Akande O, Antoun G, Mao J-X, Buolamwini J: Molecular cloning, characterisation and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. J Biol Chem 1997;272:10004–10012.
  79. Srivastava SK, Singhal SS, Hu X, Awasthi YC, Zimniak P, Singh SV: Differential catalytic efficiency of allelic variants of human glutathione S-transferase Pi in catalyzing the glutathione conjugation of thiotepa. Arch Biochem Biophys 1999;366:89–94.

    External Resources

  80. Harries LW, Stubbins MJ, Forman D, Howard GCW, Wolf CR: Identification of genetic polymorphism at the GSTP1 locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 1997;18:641–644.
  81. Watson MA, Stewart RK, Smith GBJ, Massey TE, Bell DA: Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 1998;19:275–280.
  82. Ji X, Blaszczyk J, Xiao B, O’Donnell R, Hu X, Herzog C, Singh SV, Zimniak P: Structure and function of residue 104 and water molecules in the xenobiotic substrate-binding site in human glutathione S-transferase P1-1. Biochemistry 1999;38:10231–10238.

    External Resources

  83. Henderson CJ, Smith AG, Ure J, Brown K, Bacon EJ, Wolf CR: Increased skin tumorigenesis in mice lacking pi class glutathione S-transferases. Proc Natl Acad Sci USA 1998;95:5275–5280.
  84. Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB: Human glutathione S-transferase Theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 1994;300:271–276.
  85. Guengerich FP, Their R, Persmark M, Taylor JB, Pemble SE, Ketterer B: Conjugation of carcinogens by Θ class glutathione S-transferases: Mechanisms and relevance to variations in human risk. Pharmacogenetics 1995;5:S103–S107.

    External Resources

  86. Coggan M, Whitbread L, Whittington A, Board P: Structure and organization of the human Theta-class glutathione S-transferase and D-dopachrome tautomerase gene complex. Biochem J 1998;334:617–623.

    External Resources

  87. Blackburn AC, Tzeng H-f, Anders MW, Board PG: Activity of four allelic forms of human glutathione S-transferase Zeta: GSTZ1a-1a possesses higher activity towards dichloroacetic acid. ISSX abstract 1999. 87 (a) Blackburn AC, Tzeng HF, Anders MW, Board PG: Discovery of a functional polymorphism in human glutathione transferase zeta by expressed sequence tag database analysis. Pharmacogenetics 2000;10:49–57. 87 (b) Sanak M, Simon HU, Szczeklik A: Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet 1997;350:1599–1600. 87 (c) Kennedy BP, Diehl RE, Boie Y, Adam M, Dixon RA: Gene characterization and promoter analysis of the human 5-lipoxygenase-activating protein (FLAP). J Biol Chem 1991;266:8511–8516.
  88. Rebbeck TR: Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1997;6:733–743.
  89. Strange RC, Fryer AA: The glutathione S-transferases: Influence of polymorphism on susceptibility to cancer; in Boffetta P, Caporaso N, Cuzick J, Lang M, Vineis P (eds): Metabolic Polymorphisms and Cancer. Lyon, IARC Scientific Publications, 1999, vol 148, pp 231–249.
  90. Esteller M, Corn PG, Urena JM, Gabrielson E, Baylin SB, Herman JG: Inactivation of glutathione S-transferase P1 gene by promoter hypermethylation in human neoplasia. Cancer Res 1998;58:4515–4518.

    External Resources

  91. Cheng L, Sturgis EM, Eicher SA, Char D, Spitz MR, Wei Q: Glutathione S-transferase polymorphisms and risk of squamous-cell carcinoma of the head and neck. Int J Cancer 1999;84:220–224.
  92. Matthias C, Jahnke V, Jones PW, Hoban PR, Alldersea JE, Worrall SF, Fryer AA, Strange RC: Cyclin D1, glutathione S-transferase and cytochrome P450 genotypes and outcome in patients with upper aerodigestive tract cancers: Assessment of the importance of individual genes using multivariate analysis. Cancer Epidemiol Biomarkers Prev 1999;8:815–823.
  93. Park JY, Muscat JE, Ren Q, Schantz SP, Harwick RD, Stern RED, Stern JC, Pike V, Richie JP, Lazarus P: CYP1A1 and GSTM1 polymorphisms and oral cancer risk. Cancer Epidemiol Biomarkers Prev 1997;6:791–797.
  94. Cotton SC, Sharp L, Little J, Brockton N; Glutathione S-transferase polymorphisms and colorectal cancer: A HuGE review. Am J Epidemiol 2000;151:7–32.1
  95. Welfare M, Adeokun M, Bassendine MF, Daly A: Polymorphisms in GSTP1, GSTM1, and GSTT1 and susceptibility to colorectal cancer. Cancer Epidemiol Biomarkers Prev 1999;8:289–292.
  96. Gertig DM, Stampfer M, Haiman C, Hennekens CH, Kelsey K, Hunter DJ: Glutathione S-transferase GSTM1 and GSTT1 polymorphisms and colorectal cancer risk: A prospective study. Cancer Epidemiol Biomarkers Prev 1998;7:1001–1005.
  97. Moisio AL, Sistonen P, Mecklin JP, Jarvinen H, Peltomaki P: Genetic polymorphisms in carcinogen metabolism and their association to hereditary nonpolyposis colon cancer. Gastroenterology 1998;115:1387–1394.
  98. Mann CLA, Davies MB, Boggild MD, Alldersea J, Fryer AA, Jones PW, Ko Ko C, Young C, Strange RC, Hawkins CP: Glutathione S-transferase polymorphisms in multiple sclerosis: Their relationship to disability. Neurology 2000;54:552–557.
  99. Howells REJ, Redman CWE, Dhar KK, Sarhanis P, Musgrove C, Jones PW, Alldersea J, Fryer AA, Hoban PR, Strange RC: Association of glutathione S-transferase GSTM1 and GSTT1 null genotypes with clinical outcome in epithelial ovarian cancer. Clin Cancer Res 1998;4:2439–2445.
  100. Layton MA, Jones PW, Alldersea J, Strange RC, Fryer AA, Dawes PT, Mattey DL: The therapeutic response to D-pencillamine in rheumatoid arthritis: Influence of glutathione S-transferase polymorphisms. Rheumatology 1999;38:43–47.
  101. Stanulla M, Schrappe M, Brechlin AM, Zimmerman M, Welte K: Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursors acute lymphoblastic leukemia: A case control study. Blood 2000;95:1222–1228.
  102. Goto I, Yoneda S, Yamamoto M, Kawajiri K: Prognostic significance of germ line polymorphisms of the CYP1A1 and glutathione S-transferase genes in patients with non-small cell lung cancer. Cancer Res 1996;56:3725–3730.

    External Resources

  103. Ramachandran S, Lear JT, Ramsay H, Smith AG, Bowers B, Hutchinson PE, Jones PW, Fryer AA, Strange RC: Presentation with multiple cutaneous basal cell carcinomas: Association of glutathione S-transferase and cytochrome P450 genotypes with clinical phenotype. Cancer Epidemiol Biomarkers Prev 1999;8:61–67.

    External Resources

  104. Fryer AA, Bianco A, Hepple M, Jones PW, Strange RC, Spiteri MA: Polymorphism at the glutathione S-transferase, GSTP1 locus: A new marker for bronchial hyperresponsiveness and asthma. Am J Respir Crit Care Med 2000;161:1437–1442.
  105. Fryer AA, Jones PW: Interactions between detoxifying enzyme polymorphisms and susceptibility to cancer; in Boffetta P, Caporaso N, Cuzick J, Lang M, Vineis P (eds): Metabolic Polymorphisms and Cancer. Lyon, IARC Scientific Publications, 1999, vol. 148, pp 303–322.


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