Abstract
It has become clear that several polymorphisms of human drug-metabolizing enzymes influence an individual’s susceptibility for chemical carcinogenesis. This review gives an overview on relevant polymorphisms of four families of drug-metabolizing enzymes. Rapid acetylators (with respect to N-acetyltransferase NAT2) were shown to have an increased risk of colon cancer, but a decreased risk of bladder cancer. In addition an association between a NAT1 variant allele (NAT⋆10, due to mutations in the polyadenylation site causing ~ two fold higher activity) and colorectal cancer among NAT2 rapid acetylators was observed, suggesting a possible interaction between NAT1 and NAT2. Glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) are polymorphic due to large deletions in the structural gene. Meta-analysis of 12 case-control studies demonstrated a significant association between the homozygous deletion of GSTM1 (GSTM1-0) and lung cancer (odds ratio: 1.41; 95% CI: 1.23-1.61). Combination of GSTM1-0 with two allelic variants of cytochrome P4501A1 (CYP1A1), CYP1A1 m2/m2 and CYP1A1 Val/Val further increases the risk for lung cancer. Indirect mechanisms by which deletion of GSTM1 increases risk for lung cancer may include GSTM1-0 associated decreased expression of GST M3 and increased activity of CYP1A1 and 1A2. Combination of GST M1-0 and NAT2 slow acetylation was associated with markedly increased risk for lung cancer (odds ratio: 7.8; 95% CI: 1.4-78.7). In addition GSTM1-0 is clearly associated with bladder cancer and possibly also with colorectal, hepatocellular, gastric, esophageal (interaction with CYP1A1), head and neck as well as cutaneous cancer. In individuals with the GSTT1-0 genotype more chromosomal aberrations and sister chromatid exchanges (SCEs) were observed after exposure to 1,3-butadiene or various haloalkanes or haloalkenes. Evidence for an association between GSTT1-0 and myelodysplastic syndrome and acute lymphoblastic leukemia has been presented. A polymorphic site of GSTP1 (valine to isoleucine at codon 104) decreases activity to several carcinogenic diol epoxides and was associated with testicular, bladder and lung cancer. Microsomal expoxide hydrolase (mEH) is polymorphic due to amino acid variation at residues 113 and 139. Polymorphic variants of mEH were associated with hepatocellular cancer (His-113 allele), ovarian cancer (Tyr-113 allele) and chronic obstructive pulmonary disease (His-113 allele). Three human sulfotransferases (STs) are regulated by genetic polymorphisms (hDHEAST, hM-PST, TS PST). Since a large number of environmental mutagens are activated by STs an association with human cancer risk might be expected.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Adams JD, LaVoie EJ, Hoffmann D (1982) Analysis of methylated polynuclear aromatic hydrocarbons by capillary gas chromatography. Influence of temperature on the pyrosynthesis of anthracene, phenanthrene and their methylated derivatives. J Chromatogr Sci 20: 274–277
Agundez JA, Olivera M, Ladero JM, Rodriguez-Lescure A, Ledesma MC, Diaz-Rubio M, Meyer UA, Benitez J (1996) Increased risk for hepatocellular carcinoma in NAT2-slow acetylators and CYP2D6-rapid metabolizers. Pharmacogenetics 6: 501–512
Ahmad H, Wilson DE, Fritz RR, Singh SV, Medh RD, Nagle GT, Awasthi YC, Kurosky A (1990) Primary and secondary analyses of glutathione S-transferase Pi from human placenta. Arch Biochem Biophys 287: 398–408
Aksoy IA, Sochorova V, Weinshilboum RM (1993) Human liver dehydroepiandrosterone sulfotransferase: nature and extent of individual variation. Clin Pharmacol Ther 54: 498–506
Alexandrie A-K, Sundberg MI, Seidegard J, Tornling G, Rannug A (1994) Genetic susceptibility to lung cancer with special emphasis on CYP lA1 and GST Ml: a study on host factors in relation to age at onset, gender and histological cancer types. Carcinogenesis 15: 1785–1790
Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, Laughlin R, Nemoto T, Michalek AM, Harrington A, et al. (1995) Cytochrome P4501A1 and glutathione S-transferase ( M1) genetic polymorphisms and postmenopausal breast cancer risk. Cancer Res 55: 3483–3485
Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, Michalek AM, Laughlin R, Nemoto T, Gillenwater KA, Harrington AM, Shields PG (1996) Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk. JAMA 276: 1511–1512
Anttila S, Hirvonen A, Vainio H, Husgafvel-Pursiainen K, Hayes JD, Ketterer B, (1993) Immunohistochemical localization of glutathione S-transferase in human lung. Cancer Res 53: 5643–5648
Anwar WA, Abdel-Rahman SZ, El-Zein RA, Mostafa HM, Au WW (1996) Genetic polymorphisms of GSTM1, CYP2E1 and CYP2D6 in Egyptian bladder cancer patients. Carcinogenesis 17: 1923–1929
Arand M, Mühlbauer R, Hengstler JG, Jäger E, Fuchs J, Winkler L, Oesch F (1996a) A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione S-transferase GSTM1 and GSTT1 polymorphisms. Anal Biochem 236: 184–186
Arand M, Wagner H, Oesch F (1996b) Asp333, Asp495, and His523 form the catalytic triad of rat soluble epoxide hydrolase. J Biol Chem 271: 4223–4229
Badawi AF, Stern SJ, Lang NP, Kadlubar FF (1996) Cytochrome P-450 and acetyltransferase expression as biomarkers of carcinogen DNA adduct levels and human cancer susceptibility. Prog Clin Biol Res 395: 109–140
Baker CA, Uno H, Johnson GA (1994) Minoxidil sulfation in the hair follicle. Skin Pharmacol 7: 335–339
Bartsch H, Rojas M, Alexander K, Camus A-M, Castegnaro C, Malaveille S, Antilla S, Hirvonen K, Husgafvel-Pursiainen E, Hietanen E, Vainio H (1995) Metabolic polymorphism affecting DNA binding and excretion of carcinogens in humans Pharmacogenetics 5: 584–590
Beetham JK, Grant D, Arand M, Garbarino J, Kiyosue T, Pinot F, Oesch F, Belknap WR, Shinozaki K, Hammock BD (1995) Gene evolution of epoxide hydrolases and recommended nomenclature. DNA Cell Biol 14: 61–71
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 S-transferase M1 (GST M1) that increases susceptibility to bladder cancer. J Nat Cancer Inst 85: 1159–1163
Bell DA, Badawi AF, Lang NP, Ilett KF, Kadlubar FF, Hirvonen A (1995) Polymorphism in the N-acetyltransferase 1 (NATI) polyadenylation signal: association of NAT*10 allele with higher N-acetylation activity in bladder and colon tissue. Cancer Res 55: 5226–5229
Blum M, Grant DM, McBridge OW, Heim M (1990) Human arylamine N-acetyltransferase genes: Isolation, chromosomal localization, and functional expression. DNA Cell Biol 9: 193–203
Brockmöller J, Kerb R, Drakoulis N, Nitz M, Roots I (1993) Genotype and phenotype of glutathione S-transferase class isoenzymes µ and pp in lung cancer patients and controls. Cancer Res 53: 1004–1011
Brockmöller J, Kerb R, Drakoulis N, Staffeldt B, Roots I (1994) Glutathione S-transferase M1 and its variants A and B as host factors of bladder cancer susceptibility: a case-control study. Cancer Res 54: 4103–4111
Brockmöller J, Cascorbi I, Kerb R, Roots I (1996a) Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases Ml and Ti, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk. Cancer Res 56: 3915–3925
Brockmöller J, Kaiser R, Kerb R, Cascorbi I, Jaeger V, Roots I (1996b) Polymorphic enzymes of xenobiotic metabolism as modulators of acquired p53 mutations in bladder cancer. Pharmacogenetics 6: 535–545
Brüning T, Lammert M, Kempkes M, Thier R, Golka K, Bolt HM (1997) Influence of polymorphisms of GSTM1 and GSTT1 for risk of renal cell cancer in workers with long-term high occupational exposure to trichloroethene. Arch Toxicol 71: 596–599
Buehler BA, Delimont D, VanWaes M, Finnell RH (1990) Prenatal prediction of risk of the fetal hydantoin syndrome. N Engl J Med 322: 1567–1572
Burchell B, Coughtrie MWH (1997) Genetic and environmental factors associated with variation of human xenobiotic glucuronidation and sulfation. Environ Health Perspect 105: 739–747
Cartwright RA (1984) Epidemiological studies on N-acetylation and C-center ring oxidation in neoplasia. In: Omenn GS, Gelboin HV (eds) Genetic variability in responses to chemical exposure. Cold Spring Harbor Laboratory New York, pp 359–369
Cascorbi I, Brockmöller J, Mrozikiewicz PM, Bauer S, Loddenkemper R, Roots I (1996) Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a susceptibility factor for lung cancer. Cancer Res 56: 3961–3966
Chen CJ, Yu MW, Liaw YF, Wang LW, Chiamprasert S, Matin F, Hirvonen A, Bell DA (1996) Chronic hepatitis B carriers with null genotypes of glutathione S-transferase M1 and Tl polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carcinoma. Am J Hum Genet 59: 128–134
Chen CL, Liu Q, Pui CH, Rivera GK, Sandlund JT, Ribeiro R, Evans WE, Relling MV (1997) Higher frequency of glutathione S-transferase deletions in black children with acute lymphoblastic leukemia. Blood 89: 1701–1707
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 theta 1 (GSTT1) gene defect. Lancet 347: 295–297
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
Chou HC, Lang NP, Kadlubar FF (1995) Metabolic activation of N-hydroxy arylamines and N-hydroxy heterocyclic amines by human sulfotransferases. Cancer Res 55: 525–529
Coutelle C, Ward PJ, Fleury B, Quattrocchi P, Chambrin H, Iron A, Couzigou P, Cassaigne A (1997) Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms. Hum-Genet 99: 319–325
Daly AK, Cholerton S, Gregory W, Idle JR (1993) Metabolic polymorphisms. Pharmacol Ther 57: 129–160
Deakin M, Eider J, Hendricksen C, Peckham D, Baldwin D, Pantin C, Wild N, Leopard P, Bell D, Jones P, Duncan H, Brannigan K, Alldersen J, Fryer AA, Strange RC (1996) Glutathione S-transferase GSTT1 genotype and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers. Carcinogenesis 17: 881–884
Dekant W, Vamvakas S (1993) Glutathione-dependent bioactivation of xenobiotics. Xenobiotica 23: 873–887
Dipple A (1995) DNA adducts of chemical carcinogens. Carcinogenesis 16: 437–441
Elexpuru-Camiruaga J, Buxton N, Kandula V, Dias PS, Campbell D, McIntosh J, Broome J, Jones P, Inskip A, Alldersea J et al (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: 4237–4239
Esteller M, Garcia A, Martinez-Palones JM, Xercavins J, Reventos J (1997) Susceptibility to endometrial cancer: influence of allelism at p53, glutathione S-transferase (GSTM1 and GSTT1) and cytochrome P-450 (CYP1A1) loci. Br J Cancer 75: 1385–1388
Evans DA (1968) Genetic variations in the acetylation of isoniazid and other drugs. Ann N Y Acad Sci 151: 723–733
Falany JL, Falany CN (1996) Regulation of estrogen sulfotransferase in human endometrial adenocarcinoma cells by progesterone. Endocrinology 137: 1395–1401
Feng Y, Wagner RJ, Fretland AJ, Becker WK, Cooley AM, Pretlow TP, Lee KJ, Hei DW (1996) Acetylator genotype (NAT2)-dependent formation of aberrant crypts in congenic Syrian hamsters administered 3,2’-dimethyl-4-aminobiphenyl. Cancer Res. 56: 527–531
Fost U, Tornqvist M, Leutbrecher M, Granath F, Hallier E, Ehrenberg L (1995) Effects of variation in detoxification rate on dose monitoring through adducts. Hum Exp Toxicol 14: 201–203
Fryer AA, Zhao L, Alldersea J, Boggild MD, Perrett CW, Clayton RN, Jones PW, Strange RC (1993) The glutathione S-transferases: polymerase chain reaction studies on the frequency of the GSTM1–0 genotype in patients with pituitary adenomas. Carcinogenesis 14: 563–566
Gaedigk A, Spielberg SP, Grant DM (1994) Characterization of the microsomal epoxide hydrolase gene in patients with anticonvulsant adverse drug reactions. Pharmacogenetics 4: 142–153
Garcia-Closas M, Kelsey KT, Wiencke JK, Xu X, Wain JC, Christiani DC (1997) A case-control study of cytochrome P450 1A1, glutathione S-transferase Ml, cigarette smoking and lung cancer susceptibility. 8: 544–553
Garcia-Saez I, Parraga A, Phillips MF, Mantle TJ, Coll M (1994) Molecular structure of 1.8 A of mouse liver class pi glutathione S-transferase complex with S-(p-nitrobenzyl)glutathione and other inhibitors. J Mol Biol 237: 298–314
Glatt H (1997) Bioactivation of mutagens via sulfation. FASEB J 11: 314–321
Glatt H, Henschler R, Frank H, Seidel A, ChengXi Y, Abu-Shqara E, Harvey RG (1993) Sulfotransferase-mediated mutagenicity of 1-hydroxymethylpyrene and 4H-cyclopenta[def]chrysen-4-ol and its enhancement by chloride anions. Carcinogenesis 14: 599–602
Glatt H, Pauly K, Frank H, Seidel A, Oesch F, Harvey RG, Werle-Schneider G (1994) Substance dependent sex differences in the activation of benzylic alcohols to mutagens by hepatic sulfotransferases of the rat. Carcinogenesis 15: 2605–2611
Glatt H, Christoph S, Czich A, Pauly K, Schwierzok A, Seidel A, Coughtrie MWH, Doehmer J, Falany CN, Phillips DH, Yamazoe Y, Bartsch I (1996) Rat and human sulfotransferases expressed in Ames’s Salmonella typhimurium strains and Chinese hamster V79 cells for the activation of mutagens. In: Hengstler JG, Oesch F (eds) Control mechanisms of carcinogenesis. Mainz, pp 98–115 (publishing by editors)
Golka K, Prior V, Blaszkewicz M, Cascorbi I, Schops W, Kierfeld G, Roots I, Bolt HM (1996) Occupational history and genetic N-acetyltransferase polymorphism in urothelial cancer patients of Leverkusen, Germany Scand J Work Environ Health 22: 332–338
Gonzalez FJ, Idle JR (1994) Pharmacogenetic phenotyping and genotyping: present status and future potential. Clin Pharmacokinet 26: 59–70
Grant DM, Josephy PD, Lord HL, Morrison LD (1992) Salmonella typhimurium strains expressing human arylamines N-acetyltransferases: metabolism and mutagenic activation of arylamines. Cancer Res 52: 3961–3964
Green VJ, Pirmohamed M, Kitteringham NR, Gaedigk A, Grant DM, Boxer M, Burchell B, Park BK (1995) Genetic analysis of microsomal epoxide hydrolase in patients with carbamazepine hypersensitivity. Biochem Pharmacol 50: 1353–1359
Guengerich FP (1996) Metabolic control of carcinogens. In: Hengstler JG, Oesch F (eds) Control mechanisms of carcinogenesis. Publishing House of the Editors, Mainz, pp 12–35
Guengerich FP, Johnson WW, Y-F Ueng, Yamazaki H, Shimada T (1996) Involvement of cytochrome P450 glutathione S-transferase, and epoxide hydrolase in the metabolism of aflatoxin 131 and relevance to risk of human liver cancer. Environ Health Perspect 104: 557–562
Hallier E, Langhof T, Dannappel D, Leutbrecher M, Schröder K, Goergens HW, Müller A, Bolt H (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: 173–178
Hand PA, Inskip A, Gilford J, Alldersea J, Elexpuru-Camiruaga J, Hayes JD, Jones PW, Strange RC, Fryer AA (1996) Allelism at the glutathione S-transferase GSTM3 locus: interactions with GSTM1 and GSTT1 as risk factors for astrocytoma. Carcinogenesis 17: 1919–1922
Harries LW, Stubbins MJ, Forman D, Howard GCW, Wolf CR (1997) Identification of genetic polymorphism at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 18: 641–644
Harrison DJ, Cantlay AM, Rae F, Lamb D, Smith CA (1997) Frequency of glutathione Stransferase M1 deletion in smokers with emphysema and lung cancer. Hum Exp Toxicol 16: 356–360
Hassett C, Aicher L, Sidhu JS, Omiecinski CJ (1994) Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants. Hum Mol Genet 3: 412–428
Hassett C, Lin J, Carty CL, Laurenzana EM, Omiecinski CJ (1997) Human hepatic microsomal epoxide hydrolase: comparative analysis of polymorphic expression. Arch Biochem Biophys 337: 275–283
Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST* and the contribution of the enzyme to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30: 445–600
Heagerty AHM, Fitzgerald D, Smith A, Bowers B, Jones P, Fryer AA, Zhao L, Alldersea J, Strange RC (1994) Glutathione S-transferase GST M1 phenotypes and protection against cutaneous tumours. Lancet 343: 266–268
Heckbert SR, Weiss NS, Hornung SK, Eaton DL, Motusky AG (1992) Glutathione S-transferase and epoxide hydrolase activity in human leukocytes in relation to risk of lung cancer and other smoking-related cancers. J Natl Cancer Inst 84: 414–422
Hein DW, Rustan TD, Ferguson RJ, Doll MA, Gray K (1994) Metabolic activation of aromatic and heterocyclic N-hydroxyarylamines by wild-type and mutant recombinant human NAT1 and NAT2 acetyltransferases. Arch Toxicol 68: 129–133
Hengstler JG, Fuchs J, Oesch F (1992) DNA strand breaks and DNA cross-links in peripheral mononuclear blood cells of ovarian cancer patients during chemotherapy with cyclophosphamide/carboplatin. Cancer Res 52: 5622–5626
Hengstler JG, Fuchs J, Oesch F (1992) DNA strand breaks and DNA cross-links in peripheral mononuclear blood cells of ovarian cancer patients during chemotherapy with cyclophosphamide/carboplatin. Cancer Res 52: 5622–5626
Hengstler JG, Fuchs J, Oesch F (1992) DNA strand breaks and DNA cross-links in peripheral mononuclear blood cells of ovarian cancer patients during chemotherapy with cyclophosphamide/carboplatin. Cancer Res 52: 5622–5626
Herrero ME, Arand M, Hengstler JG, Oesch F (1997) Recombinant expression of human microsomal epoxide hydrolase protects V79 Chinese hamster cells from styrene oxide-induced but not from ethylene oxide-induced DNA strand breaks. Environ Molecul Mutag 30: 429–439
Hickman D, Sim E (1991) N-Acetyltransferase polymorphism. Comparison of phenotype and genotype in humans. Biochem Pharmacol 42: 1007–1014
Hirvonen A, Nylund L, Kociba P, Husgafvel-Pursiainen K, Vainio H (1994) Modulation of urinary mutagenicity by genetically determined carcinogen metabolism in smokers. Carcinogenesis 15: 813–815
Hirvonen A, Pelin K, Tammilehto L, Karjalainen A, Mattson K, Linnainmaa K (1995) Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res 55: 2981–2983
Hirvonen A, Saarikoski ST, Linnainmaa K, Koskinen K, Husgafvel-Pursiainen K, Mattson K, Vainio H (1996) Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders. J Natl Cancer Inst 88: 1853–1856
Holler R, Arand M, Mecky A, Oesch F, Friedberg T (1997) The membrane anchor of microsomal epoxide hydrolase from human, rat, and rabbit displays an unexpected membrane topology. Biochem Biophys Res Commun 236: 754–759
Hsieh LL, Huang RC, Yu MW, Chen CJ, Liaw YF (1996) L-myc, GST Ml genetic polymorphism and hepatocellular carcinoma risk among chronic hepatitis B carriers. Cancer Lett 103: 171–176
Hu X, O’Donnell R, Srivastava SK, Xia H, Zimniak P, Nanduri B, Bleicher RJ, Awasthi S, Awasthi YC, Ji X, Singh SV (1997a) 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 7beta, 8alpha-dihydroxy-9alpha, 10alpha-oxy7,8,9,10-tetrahydrobenzo[a]pyrene. Biochem. Biophys Res Commun 235: 424–428
Hu X, Ji X, Srivastava SK, Xia H, Awasthi S, Nanduri B, Awasthi YC, Zimniak P, Singh SV (1997b) Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1–1 in the glutathione conjugation of carcinogenic diol epoxide of chrysene. Arch Biochem Biophys 345: 32–38
Izawa I, Ali-Osman F (1993) Structure of glutathione S-transferase Pi gene cloned from a malignant glioma cell line ( Abstr ). Proc Ann Meet Assoc Cancer Res 34: A2030
Jahnke V, Strange R, Matthias C, Fryer A (1997) Glutathione S-transferase and cytochrome P450 genotypes as risk factors for laryngeal carcinoma. Eur Arch Otorhinolaryngol Suppl 1: 147–149
Johnson WW, Yamazaki H, Shimada T, Ueng Y-F, Guengerich FP (1997) Aflatoxin B1 8,9-epoxide hydrolysis in the presence of rat and human epoxide hydrolase. Chem Res Toxicol 10: 672–676
Kadlubar FF, Badawi AF (1995) Genetic susceptibility and carcinogen-DNA adduct formation in human urinary bladder carcinogenesis. Toxicol Lett 82 /83: 627–632
Karakaya AE, Cok I, Sardas S, Gogus OS (1989) N-Acetyltransferase phenotype of patients with bladder cancer. Hum Toxicol 5: 333–335
Katoh T, Inatomi H, Nagaoka A, Sugita A (1995) Cytochrome P4501A1 gene polymorphism and homozygous deletion of the glutathione S-transferase MI gene in urothelial cancer patients. Carcinogenesis 16: 655–657
Katoh T, Nagata N, Kuroda Y, Itoh H, Kawahara A, Kuroki N, Ookuma R, Bell DA (1996) Glutathione S-transferase MI (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. Carcinogenesis 17: 1855–1859
Kawajiri K, Nakachi K, Imai K, Watanabe J, Hayashi S (1993) The CYP1A1 gene and cancer susceptibility. Crit Rev Oncol Hematol 14: 77–87
Kelsey KT, Spitz MR, Zuo ZF, Wiencke JK (1997a) Polymorphisms in the glutathione Stransferase class mu and theta genes interact and increase susceptibility to lung cancer in minority populations. Cancer Causes Control 8: 554–559
Kelsey KT, Hankinson SE, Colditz GA, Springer K, Garcia-Closas M, Spiegelman D, Manson JE, Garland M, Stampfer MJ, Willett WC, Speizer FE, Hunter DJ (1997b) Glutathione Stransferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases. Cancer Epidemiol Biomarkers Prey 6: 511–515
Kempkes M, Wiebel FA, Golka K, Heitmann P, Bolt HM (1996a) Comparative genotyping and phenotyping of glutathione S-transferase GST Ti. Arch Toxicol 70: 306–309
Kempkes M, Golka K, Reich S, Reckwitz T, Bolt (1996b) Glutathione S-transferase GSTM1 and GSTT1 null genotypes as potential risk factors for urothelial cancer of the bladder. Arch Toxicol 71: 123–126
Kerdar RS, Fasshauer I, Probst M, Blum M, Meyer UA, Wild D (1993) 32P-postlabelling studies on the DNA adducts of the food mutagens/carcinogens IQ and PhIP-adduct formation in a chemical system, and by rat and human metabolism. IARC Sci Publ 124:173–179
Kihara M, Kihara M, Noda K (1995a) Risk of smoking for squamous and small cell carcinomas of the lung modulated by combinations of CYP 1A1 and GST Ml gene polymorph-isms in a Japanese population. Carcinogenesis 16: 2331–2336
Kihara M, Noda K, Kihara M (1995b) Distribution of GST Ml null genotype in relation to gender, age and smoking status in Japanese lung cancer patients. Pharmacogenetics 5: 74–79
Kihara M, Kihara M, Kubota A, Furukawa M, Kimura H (1997) GSTM1 gene polymorphism as a possible marker for susceptibility to head and neck cancers among Japanese smokers. Cancer Lett 112: 257–262
Kiyohara C, Hirohata T (1994) A role of hydrocarbon hydroxylase inducibility in susceptibility to lung carcinogenesis. Jpn J Hyg 48: 1027–1036
Kroetz DL, McFarland LV, Kerr BM, Levy RH (1990) Distribution of microsomal epoxide hydrolase (mEH) activity in healthy Caucasian subjects. Clin Pharmacol Ther 47: 160
Lacourciere GM, Armstrong RN (1994) Microsomal and soluble epoxide hydrolases are mem- bers of the same family of C-X bond hydrolase enzymes. Chem Res Toxicol 7: 121–124
Lancaster JM, Brownlee HA, Bell DA, Futreal A, Marks JR, Berchuck A, Wiseman RW, Taylor JA (1996) Microsomal epoxide hydrolase polymorphism as a risk factor for ovarian cancer. Mol Carcinog 17: 160–162
Lear JT, Smith AG, Heagerty AH, Bowers B, Jones PW, Gilford J, Alldersea J, Strange RC, Fryer AA (1997) Truncal site and detoxifying enzyme polymorphisms significantly reduce time to presentation of further primary cutaneous basal cell carcinoma. Carcinogenesis 18: 1499–1503
Lin HJ, Han C-Y, Bernstein DA, Hsiao W, Lin BK, Hardy S (1994) Ethnic distribution of the glutathione transferase Mu 1–1 (GSTM1) null genotype in 1473 individuals and application to bladder cancer susceptibility. Carcinogenesis 15: 1077–1081
Lin HJ, Probst-Hensch M, Ingles SA, Han C, Lin BK, Lee DB, Frankl HD, Lee ER, Longnecker MP, Haile RW (1995) Glutathione S-transferase (GST M1) null genotype, smoking, and prevalence of colorectal adenomas. Cancer Res 55: 1224–1226
London SJ, Daly AK, Cooper J, Navidi WC, Carpenter CL, Idle JR (1995) Polymorphism of glutathione S-transferase Ml and lung cancer risk among African-Americans and Caucasians in Los Angeles County, California. J Natl Cancer Inst 87: 1246–1253
MacLeod S, Sinha R, Kadlubar FF, Lang NP (1997) Polymorphisms of CYP1A1 and GSTM1 influence the in vivo function of CYP1A2. Mutat Res 376: 135–142
Martinez C, Agundez JA, Olivera M, Martin R, Ladero JM, Benitez J (1995) Lung cancer and mutations at the polymorphic NAT2 gene locus. Pharmacogenetics 5: 207–214
McGlynn KA, Rosvold EA, Lustbader ED, Hu Y, Clapper ML, Zhou T, Wild C, Xia X-L, Baffoe-Bonnie A, Ofori-Adjei D, Chen G-C, London WT, Sheen F-M, Buetow KH (1995) Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1. Proc Natl Acad Sci USA 92: 2384–2387
McWilliams JE, Sanderson BJ, Harris EL, Richert-Boe KE, Henner-WD (1995) Glutathione S-transferase Ml (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prey 4: 589–594
Medina JF, Wetterholm A, Radmark O, Shapiro R, Haeggstrom JZ, Vallee BL, Samuelsson B (1991) Leukotriene A4 hydrolase: determination of the three zinc-binding ligands by site-directed mutagenesis and zinc analysis. Proc Natl Acad Sci USA 88: 7620–7624
Mertes I, Fleischmann R, Glatt HR, Oesch F (1985) Interindividual variations in the activities of cytosolic and microsomal epoxide hydrolase in human liver. Carcinogenesis 6: 219–223
Miller JA (1994) Sulfonation in chemical carcinogenesis–history and present status. Chem Biol Interact 92: 329–341
Minchin RF, Reeves PT, Teitel CH, McManus ME, Mojarabbi B, Ilett KF, Kadlubar FF (1992) N- and 0-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells. Biochem. Biophys Res Commun 185: 839–844
Moreira A, Martins G, Monteiro MJ, Alves M, Dias J, DaCosta JD, Melo MJ, Matias D, Costa A, Cristovao M, Rueff J, Monteiro C (1996) Glutathione S-transferase mu polymorphism and susceptibility to lung cancer in the Portuguese population. Teratogenesis Carcinog Mutagen 16: 269–274
Morita S, Yano M, Shiozaki H, Tsujinaka T, Ebisui C, Morimoto T, Kishibuti M et al (1997) CYP1A1, CYP2E1 and GSTM1 polymorphisms are not associated with susceptibility to squamous-cell carcinoma of the esophagus. Int J Cancer 71: 192–195
Nakajima T, Elovaara E, Anttila S, Hirvonen A, Camus A-M, Hayes JD, Ketterer B, Vainio H (1995) Expression and polymorphism of glutathione S-transferase in human lungs: risk factors in smoking-related lung cancer. Carcinogenesis 16: 707–711
Nazar-Stewart V, Motulsky AG, Eaton DL, White E, Hornung SK, Long ZT, Stapelton P, Weiss NS (1993) The glutathione S-transferase u polymorphism as a marker for susceptibility to lung carcinoma. Cancer Res 53: 2313–2318
Nebert DW (1991) Identification of genetic differences in drug metabolism: prediction of individual risk of toxicity or cancer. Hepatology 14: 398–401
Nebert DW, McKinnon RA, Puga A (1996) Human drug-metabolizing polymorphisms: effects on risk of toxicology and cancer. DNA Cell Biol 15: 273–280
Nerurkar PV, Schutt HA, Anderson LM, Riggs CW, Snyderwine EG, Thorgeirsson SS, Weber WW, Rice JM, Levy GN (1995) DNA adducts of 2-amino-3-methylimidazo[4,5-quinoline ( IQ) in colon, bladder, and kidney of congenic mice differing in Ah responsiveness and N-acetyltransferase genotype. Cancer Res 55: 3043–3049
Nimura Y, Yokoyama S, Fujimori M, Aoki T, Adachi W, Nasu T, He M, Ping YM, Iida F (1997) Genotyping of the CYP1A1 and GSTM1 genes in esophageal carcinoma patients with special reference to smoking. Cancer 80: 852–857
Oesch F (1988) Antimutagenesis by shift in monooxygenase isoenzymes and induction of microsomal epoxide hydrolase. Mutat Res 202: 335–342
Oesch F, Timms CW, Walker CH, Guenther TM, Sparrow A, Watabe T, Wolf CR (1984) Existance of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities. Carcinogenesis 5: 7–9
Oesch F, Fuchs J, Arand M, Gebhard S, Hallier A, Oesch-Bartlomowicz B, Jung D, Tanner B, Bolm-Audorff U, Hiltl G, Bienfait G, Konietzko J, Hengstler JG (1997) Möglichkeiten and Grenzen der alkalischen Filterelution zum Biomonitoring gentoxischer Belastungen. In: Bundesanstalt für Arbeitsschutz and Arbeitsmedizin (ed) Molekulare Marker bei beruflich verursachten Tumoren. Bundesanstalt für Arbeitsschutz, Berlin
Okkels H, Sigsgaard T, Wolf H, Autrup H (1996) Glutathione S-transferase (as a risk factor in bladder tumours. Pharmacogenetics 6: 251–256
Okkels H, Sigsgaard T, Wolf H, Autrup H (1997) Arylamine N-acetyltransferase u (NATO and 2 (NAT2) polymorphisms in susceptibility to bladder cancer: the influence of smoking. Cancer Epidemiol Biomarkers Prey 6: 225–231
Pemble S, Schroeder 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: 271–276
Perrett CW, Clayton RN, Pistorello M, Boscaro M, Scanarini M, Bates AS, Buckley N, Jones P, Fryer AA, Gilford J et al (1995) GSTM1 and CYP2D6 genotype frequencies in patients with pituitary tumours: effects on p53 and ras. Carcinogenesis 16: 1643–1645
Peter H, Deutschmann S, Reichel C, Hallier E (1989) Metabolism of methyl chloride by human erythrocytes. Arch Toxicol 63: 351–355
Preudhomme C, Nisse C, Hebbar M, Vanrumbeke M, Brizard A, Lai JL, Fenaux P (1997) Glutathione S-transferase theta 1 gene defects in myelodysplastic syndromes and their correlation with karyotype and exposure to potential carcinogens. Leukemia 11: 1580–1582
Price RA, Cox NJ, Spielman RS, Van Loon J, Maidak BL, Weinshilboum RM (1988) Inheritance of human platelet thermolabile phenol sulfotransferase ( TL PST) activity. Genet Epidemiol 5: 1–15
Probst-Hensch NM, Haile RW, Li DS, Sakamoto GT, Louie AD, Lin BK, Frankl HD, Lee ER, Lin HL (1996) Lack of association between the polyadenylation polymorphism in the NAT1 (acetyltransferase 1) gene and colorectal adenomas. Carcinogenesis 17: 2125–2129
Ramdahl T (1985) Polycyclic aromatic ketones in source emissions and ambient air. In: Cooke M, Dennis AJ (eds) Polynuclear aromatic hydrocarbons: mechanisms, methods and metabolism. Battelle, Columbus, OH, pp 1075–1087
Rebbeck TR (1997) Molecular epidemiology of the human glutathione S-transferase genotypes GST M1 and GST T1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prey 6: 733–743
Roberts-Thomson IC, Ryan P, Khoo KK, Hart WJ, McMichael AJ, Butler RN (1996) Diet, acetylator phenotype, and risk of colorectal neoplasia. Lancet 347: 1372–1374
Ross RK, Jones PA, Yu MC (1996) Bladder cancer epidemiology and pathogenesis. Semin Oncol 23: 536–545
Rothman N, Hayes RB, Zenser TV, DeMarini DM, Bi W, Hirvonen A, Talaska G, Bhatnagar VK, Caporaso NE, Brooks LR, Lakshmi VM, Feng P, Kashyap SK, You X, Eischen BT, Kashyap R, Shelton ML, Hsu FF, Jaeger M, Parikh DJ, Davis BB, Yin S, Bell DA (1996) The glutathione S-transferase M1 (GSTM1) null genotype and benzidine-associated bladder cancer, urine mutagenicity, and exfoliated urothelial cell DNA adducts. Cancer Epidemiol. Biomarkers Prey 5: 979–983
Ryberg D, Skaug V, Hewer A, Phillips DH, Harries LW, Wolf CR, Ogreid D, Ulvik A, Vu P, Haugen A (1997) Genotypes of glutathione transferase Mi and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis 18: 1285–1289
Sabbioni G, Skipper PL, Büchi G, Tannenbaum SR (1987) Isolation and characterization of the major serum albumin adduct formed by aflatoxin B1 in vivo in rats. Carcinogenesis 8: 819–824
Sadrieh N, Davis CD, Snyderwine EG (1996) N-acetyltransferase expression and metabolic activation of the food-derived heterocyclic amines in the mammary gland. Cancer Res 56: 2683–2687
Sarhanis P, Redman C, Perrett C, Brannigan K, Clayton RN, Hand P, Musgrove C, Suarez V, Jones P, Fryer AA, Farrell WE, Strange RC (1996) Epithelial ovarian cancer: influence of polymorphism at the glutathione S-transferase GSTM1 and GSTT1 loci on p53 expression. Br J Cancer 74: 1757–1761
Schröder KR, Wiebel FA, Reich S, Dannappel D, Bolt HM, Hallier E (1995) Glutathione-Stransferase ( GST) theta polymorphism influences background SCE rate. Arch Toxicol 69: 505–507
Schröder KR, Hallier E, Meyer DJ, Wiebel FA, Muller AM, Bolt HM (1996) Purification and characterization of a new glutathione S-transferase, class theta, from human erythrocytes. Arch Toxicol 70: 559–566
Seidegard J, Ekström G (1997) The role of human glutathione transferases and epoxide hydrolases in the metabolism of xenobiotics. Environ Health Perspect 105: 791–799
Seidegard J, DePierre JW, Pero RW (1984) Measurement and characterization of membrane-bound and soluble epoxide hydrolase activities in resting mononuclear leucocytes from human blood. Cancer Res 44: 3654–3660
Seidegard J, Pero RW, Miller DG, Beattie EJ (1986) A glutathione transferase in human leucocytes as a marker for the susceptibility to lung cancer. Carcinogenesis 7: 751–753
Seidegard J, Vorachek WR, Pero RW, Pearson WR (1988) Hereditary difference in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion. Proc Natl Acad Sci USA 85: 7203–7207
Seidegard J, Pero RW, Markowitz MM, Roush G, Miller DG, Beattie EJ (1990) Isoenzymes of glutathione transferase (class tt) as a marker for the susceptibility to lung cancer: a follow up study. Carcinogenesis 11: 33–36
Silverman DT, Hartge P, Morrison AS et al (1992) Epidemiology of bladder cancer. Hematol Oncol Clin North Am 6: 1–30
Sinha R, Rothman N, Brown ED, Mark SD, Hoover RN, Caporaso NE, Levander OA, Knize MG, Lang NP, Kadlubar FF (1994) Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501A2 activity in humans. Cancer Res 54: 6154–6159
Smith CAD, Harrison DJ (1997) Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema. Lancet 350: 630–633
Sorsa M, Osterman-Golkar S, Peltonen K, Saarikoski ST, Sram R (1996) Assessment of exposure to butadiene in the process industry. Toxicology 113: 77–83
Stahl F, Schnorr D, Pilz C, Dorner G (1992) Dehydroepiandrosterone ( DHEA) levels in patients with prostatic cancer, heart diseases and under surgery stress. Exp Clin Endocrinol 92: 68–70
Sundaram RS, Van Loon JA, Tucker R, Weinshilboum RM (1989) Sulfation pharmacogenetics: correlation of human platelet and small intestinal phenol sulfotransferase. Clin Pharmacol Ther 46: 501–509
Tanner B, Hengstler JG, Dietrich B, Henrich M, Steinberg P, Weikel W, Meinert R, Kaina B, Oesch F, Knapstein PG (1997) Glutathione, glutathione S-transferase a and n, and aldehyde dehydrogenase content in relationship to drug resistance in ovarian cancer. Gynecol Oncol 65: 54–62
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: 163166
To-Figueras J, Gene M, Gomez-Catalan J, Galan C, Firvida J, Fuentes M, Rodamilans M, Huguet E, Estape J, Corbella J (1996) Glutathione-S-transferase M1 and codon 72 p53 polymorphisms in a northwestern Mediterranean population and their relation to lung cancer susceptibility. Cancer Epidemiol Biomarkers Prey 5: 337–342
To-Figueras J, Gene M, Gomez-Catalan J, Galan MC, Fuentes M, Ramon JM, Rodamilans M, Huguet E, Corbella J (1997) Glutathione S-transferase M1 and T1 polymorphisms and lung cancer risk among Northwestern Mediterraneans. Carcinogenesis 18: 1529–1533
Trizna Z, Clayman GL, Spitz MR, Briggs KL, Goepfert H (1995) Glutathione S-transferase genotypes as risk factors for head and neck cancer. Am J Surg 170: 499–501
Turesky R, Lang NP, Butler MA, Teitel CH, Kadlubar FF (1991) Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon. Carcinogenesis 12: 1839–1845
Van Loon JA, Weinshilboum RM (1984) Human platelet phenol sulfotransferase: familial variation in the thermal stability of the TS form. Biochem Genet 22: 997–1014
Vatsis KP, Martelli KJ, Weber WW (1991) Diverse point mutations in the human gene for polymorphic N-acetyltransferase. Proc Natl Acad Sci USA 88: 6333–6337
Vaury C, Laine R, Noguiez P, DeCoppet P, Jaulitz C, Praz F, Pompon D, Amor-Gueret M (1995) Human glutathione S-transferase M1 null genotype is associated with a high inducibility of cytochrome P450 lAl gene transcription. Cancer Res 55: 5520–5523
Vineis P, McMichael A (1996) Interplay between heterocyclic amines in cooked meat and metabolic phenotype in the etiology of colon cancer. Cancer Causes Control 7: 479–478
Warwick A, Sarhanis P, Redman C, Pemble S, Taylor JB, Ketterer B, Jones P, Alldersea J, Gil-ford J, Yengi L et al (1994) Theta class glutathione S-transferase GSTT1 genotypes and susceptibility to cervical neoplasia: interactions with GSTM1, CYP2D6 and smoking. Carcinogenesis 15: 2841–2845
Weber WW, Hein DW (1985) N-Acetylation pharmacogenetics. Pharmacol Rev 37:25–79
Weinshilboum RM, Otterness DM, Aksoy IA, Wood TC, Her C, Raftogianis RB (1997) FASEB J 11: 3–14
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 Prey 4: 253–259
Wiencke JK, Wrench MR, Mike R, Zuo Z, Kelsey KT (1997) Population-based study of glutathione S-transferase mu gene deletion in adult glioma cases and controls. Carcinogenesis 18: 1431–1433
Wild D, Feser W, Michel S, Lord HL, Josephy PD (1995) Metabolic activation of heterocyclic aromatic amines catalyzed by human arylamine N-acetyltransferase isozymes (NAT1 and NAT2) expressed in Salmonella typhimurium. Carcinogenesis 16: 643–648
Wood TC, Her C, Aksoy I, Otterness DM, Weinshilboum RM (1996) Human dehydroepiandrosterone sulfotransferase pharmacogenetics: quantitative Western analysis and gene sequence polymorphisms. J Steroid Biochem Molec Biol 59: 467–478
Wu RW, Tucker JD, Sorensen KJ, Thompson LH, Felton JS (1997) Differential effects of acetyltransferase expression on the genotoxicity of heterocyclic amines in CHO cells. Mutat Res 390: 93–103
Yamazoe Y, Nagata K, Ozawa S, Kato R (1994) Structural similarity and diversity of sulfotransferases. Chem Biol Interact 92: 107–117
Yanagawa Y, Sawada M, Deguchi T, Gonzalez FJ, Kamataki T (1994) Stable expression of human CYP1A2 and N-acetyltransferases in Chinese hamster CHL cells: mutagenic activation of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-flquinoxaline Cancer Res 54: 3422–3427
Yengi L, Inskip A, Gilford J, Alldersea J, Bailey L, Smith A, Lear JT, Heagerty AH, Bowers B, Hand P, Hayes JD, Jones PW, Strange RC, Fryer AA (1996) Polymorphism at the glutathione S-transferase locus GSTM3: interaction with cytochrome P450 and glutathione Stransferase genotypes as risk factors for multiple cutaneous basal cell carcinoma. Cancer Res 56: 1974–1979
Young WF, Laws ER, Sharbrough FW, Weinshilboum RM (1985) Human phenol sulfotransferase: correlation of brain and platelet activities. J Neurochem 44: 1131–1137
Yu MW, Gladek-Yarborough A, Chiamprasert S, Santella RM, Liaw YF, Chen CJ (1995) Cytochrome P450 2E1 and glutathione S-transferase Ml polymorphisms and susceptibility to hepatocellular carcinoma. Gastroenterology 109: 1266–1273
Zhong S, Howie AF, Ketterer B, Taylor J, Hayes JD, Beckett GJ, Wathen CG, Wolf CR, Spurr NK (1991) Glutathione S-transferase yc locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility. Carcinogenesis 12: 1533–1537
Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK (1993) Relationship between GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14: 1821–1824
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer-Verlag Berlin · Heidelberg
About this paper
Cite this paper
Hengstler, J.G., Arand, M., Herrero, M.E., Oesch, F. (1998). Polymorphisms of N-Acetyltransferases, Glutathione S-Transferases, Microsomal Epoxide Hydrolase and Sulfotransferases: Influence on Cancer Susceptibility. In: Schwab, M., Rabes, H.M., Munk, K., Hofschneider, H.P. (eds) Genes and Environment in Cancer. Recent Results in Cancer Research, vol 154. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-46870-4_4
Download citation
DOI: https://doi.org/10.1007/978-3-642-46870-4_4
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-46872-8
Online ISBN: 978-3-642-46870-4
eBook Packages: Springer Book Archive