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J Clin Pathol. Apr 1998; 51(4): 294–298.
PMCID: PMC500672

Genetic polymorphism of N-acetyltransferase-2, glutathione S-transferase-M1, and cytochromes P450IIE1 and P450IID6 in the susceptibility to head and neck cancer.

Abstract

AIMS: To analyse the allele frequencies of DNA polymorphisms at the genes for cytochromes P450IIE1 and P450IID6, N-acetyltransferase-2, and glutathione S-transferase-M1 in patients with head and neck squamous cell carcinoma, in an attempt to define genetic factors involved in the susceptibility to this cancer, which is strongly associated with tobacco consumption. METHODS: Determination of restriction fragment length polymorphism (RFLP) at cytochromes P450IIE1/P450IID6 and NAT2 genes, and the presence of homozygous deletion of the GSTM1 gene, in 200 controls and 75 head and neck cancer patients. Allelic frequencies between the two groups were compared using a chi 2 test, and odds ratio with 95% confidence intervals were calculated. RESULTS: There was no evidence of an association between alleles of CYP2D6 and CYP2E1 and head and neck cancer in our population. Similarly, frequencies of individuals lacking the GSTM1 gene did not differ between controls and patients. However, individuals with the NAT2-SA phenotype were at higher risk of developing head and neck cancer. The frequencies of the most common SA genotype (homozygous for the NAT2*5 allele) were higher in patients than in controls (27% v 15%, respectively). Slow acetylators homozygous for the NAT2*6 allele, the second most common SA allele, were also more common in patients than in controls (11% v 5%, respectively). CONCLUSIONS: Slow NAT2 activity is a risk factor possibly leading to the development of head and neck cancer in response to tobacco carcinogens.

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  • Smith CA, Smith G, Wolf CR. Genetic polymorphisms in xenobiotic metabolism. Eur J Cancer. 1994;30A(13):1921–1935. [PubMed]
  • Smith CA, Gough AC, Leigh PN, Summers BA, Harding AE, Maraganore DM, Sturman SG, Schapira AH, Williams AC, Maranganore DM, et al. Debrisoquine hydroxylase gene polymorphism and susceptibility to Parkinson's disease. Lancet. 1992 Jun 6;339(8806):1375–1377. [PubMed]
  • Wolf CR, Smith CA, Bishop T, Forman D, Gough AC, Spurr NK. CYP2D6 genotyping and the association with lung cancer susceptibility. Pharmacogenetics. 1994 Apr;4(2):104–106. [PubMed]
  • Caporaso N, Hayes RB, Dosemeci M, Hoover R, Ayesh R, Hetzel M, Idle J. Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype. Cancer Res. 1989 Jul 1;49(13):3675–3679. [PubMed]
  • Agúndez JA, Ledesma MC, Benítez J, Ladero JM, Rodríguez-Lescure A, Díaz-Rubio E, Díaz-Rubio M. CYP2D6 genes and risk of liver cancer. Lancet. 1995 Apr 1;345(8953):830–831. [PubMed]
  • Kato S, Shields PG, Caporaso NE, Hoover RN, Trump BF, Sugimura H, Weston A, Harris CC. Cytochrome P450IIE1 genetic polymorphisms, racial variation, and lung cancer risk. Cancer Res. 1992 Dec 1;52(23):6712–6715. [PubMed]
  • Hirvonen A, Husgafvel-Pursiainen K, Anttila S, Karjalainen A, Vainio H. The human CYP2E1 gene and lung cancer: DraI and RsaI restriction fragment length polymorphisms in a Finnish study population. Carcinogenesis. 1993 Jan;14(1):85–88. [PubMed]
  • Vineis P, Bartsch H, Caporaso N, Harrington AM, Kadlubar FF, Landi MT, Malaveille C, Shields PG, Skipper P, Talaska G, et al. Genetically based N-acetyltransferase metabolic polymorphism and low-level environmental exposure to carcinogens. Nature. 1994 May 12;369(6476):154–156. [PubMed]
  • Blum M, Demierre A, Grant DM, Heim M, Meyer UA. Molecular mechanism of slow acetylation of drugs and carcinogens in humans. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5237–5241. [PMC free article] [PubMed]
  • Hein DW, Doll MA, Rustan TD, Ferguson RJ. Metabolic activation of N-hydroxyarylamines and N-hydroxyarylamides by 16 recombinant human NAT2 allozymes: effects of 7 specific NAT2 nucleic acid substitutions. Cancer Res. 1995 Aug 15;55(16):3531–3536. [PubMed]
  • Hein DW, Ferguson RJ, Doll MA, Rustan TD, Gray K. Molecular genetics of human polymorphic N-acetyltransferase: enzymatic analysis of 15 recombinant wild-type, mutant, and chimeric NAT2 allozymes. Hum Mol Genet. 1994 May;3(5):729–734. [PubMed]
  • Cascorbi I, Drakoulis N, Brockmöller J, Maurer A, Sperling K, Roots I. Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity. Am J Hum Genet. 1995 Sep;57(3):581–592. [PMC free article] [PubMed]
  • Risch A, Wallace DM, Bathers S, Sim E. Slow N-acetylation genotype is a susceptibility factor in occupational and smoking related bladder cancer. Hum Mol Genet. 1995 Feb;4(2):231–236. [PubMed]
  • Ilett KF, David BM, Detchon P, Castleden WM, Kwa R. Acetylation phenotype in colorectal carcinoma. Cancer Res. 1987 Mar 1;47(5):1466–1469. [PubMed]
  • Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, Michalek AM, Laughlin R, Nemoto T, Gillenwater KA, et al. Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk. JAMA. 1996 Nov 13;276(18):1494–1501. [PubMed]
  • Hein DW. Acetylator genotype and arylamine-induced carcinogenesis. Biochim Biophys Acta. 1988 Aug 3;948(1):37–66. [PubMed]
  • Hayes JD, Wolf CR. Molecular mechanisms of drug resistance. Biochem J. 1990 Dec 1;272(2):281–295. [PMC free article] [PubMed]
  • Drózdz M, Gierek T, Jendryczko A, Pilch J, Piekarska J. N-acetyltransferase phenotype of patients with cancer of the larynx. Neoplasma. 1987;34(4):481–484. [PubMed]
  • Comstock KE, Sanderson BJ, Claflin G, Henner WD. GST1 gene deletion determined by polymerase chain reaction. Nucleic Acids Res. 1990 Jun 25;18(12):3670–3670. [PMC free article] [PubMed]
  • Heckbert SR, Weiss NS, Hornung SK, Eaton DL, Motulsky AG. 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. 1992 Mar 18;84(6):414–422. [PubMed]
  • Seidegård J, Pero RW, Miller DG, Beattie EJ. A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer. Carcinogenesis. 1986 May;7(5):751–753. [PubMed]
  • Cascorbi I, Brockmöller J, Mrozikiewicz PM, Bauer S, Loddenkemper R, Roots I. Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a susceptibility factor for lung cancer. Cancer Res. 1996 Sep 1;56(17):3961–3966. [PubMed]
  • Gonzalez FJ. Genetic polymorphism and cancer susceptibility: fourteenth Sapporo Cancer Seminar. Cancer Res. 1995 Feb 1;55(3):710–715. [PubMed]
  • González MV, Pello MF, López-Larrea C, Suárez C, Menéndez MJ, Coto E. Loss of heterozygosity and mutation analysis of the p16 (9p21) and p53 (17p13) genes in squamous cell carcinoma of the head and neck. Clin Cancer Res. 1995 Sep;1(9):1043–1049. [PubMed]
  • González MV, Pello MF, López-Larrea C, Suárez C, Menéndez MJ, Coto E. Deletion and methylation of the tumour suppressor gene p16/CDKN2 in primary head and neck squamous cell carcinoma. J Clin Pathol. 1997 Jun;50(6):509–512. [PMC free article] [PubMed]
  • Hickman D, Risch A, Buckle V, Spurr NK, Jeremiah SJ, McCarthy A, Sim E. Chromosomal localization of human genes for arylamine N-acetyltransferase. Biochem J. 1994 Feb 1;297(Pt 3):441–445. [PMC free article] [PubMed]

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