Journal Article

Genetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasias

M.C. Lemos, F.J. Cabrita, H.A. Silva, M. Vivan, F. Plácido and F.J. Regateiro

in Carcinogenesis

Volume 20, issue 7, pages 1225-1229
Published in print July 1999 | ISSN: 0143-3334
Published online July 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.7.1225
Genetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasias

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Xenobiotic-metabolizing enzymes constitute an important line of defence against a variety of carcinogens. Many are polymorphic, constituting the basis for the wide inter-individual variation in metabolic capacity and possibly a source of variation in the susceptibility to chemical-induced carcinogenesis. The aim of this study was to determine the existence of any association between the main genetic polymorphisms of cytochrome P450 2D6 (CYP2D6), glutathione S-transferase M1 (GSTM1) and N-acetyltransferase 2 (NAT2) and an altered risk for haematological neoplasias. A total of 160 patients and 128 controls were genotyped by means of PCR–RFLP-based assays. Mutated alleles comprising CYP2D6*4, GSTM1*0, NAT2*5A, *5B, *5C, *6 and *7 were analysed along with the wild-type alleles. The results showed a higher frequency of CYP2D6 extensive metabolizers carrying two functional alleles in the leukaemia group, when compared with controls (76.6 versus 57.0%, P = 0.008). No differences were found in the case of Hodgkin and non-Hodgkin lymphomas. Analysis of the GSTM1 and NAT2 polymorphisms failed to show an association with any of the neoplasias, although a near significant increase in fast acetylators was also found in the leukaemia group (50.0 versus 35.9%, P = 0.06). The results suggest an association of extensive metabolism with an increased risk for leukaemia, possibly by an increase in the metabolic activation of chemical carcinogens or linkage to another cancer-causing gene. Opposite findings presented in other studies may reflect geographical differences in the type of environmental carcinogens to which different populations are exposed.

Keywords: CYP2D6, cytochrome P450 2D6; EM, extensive metabolizer; GSTs, glutathioneS-transferases; GSTM1, glutathioneS-transferase M1; NATs,N-acetyltransferases; NAT2,N-acetyltransferase 2; PM, poor metabolizer.

Journal Article.  3749 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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