Carcinogenesis, Vol. 20, No. 7, 1225-1229,
July 1999
© 1999 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Genetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasias
Medical Genetics Unit, Faculty of Medicine, University of Coimbra, and
1 Department of Clinical Haematology, University Hospital of Coimbra, 3049 Coimbra Codex, Portugal
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.
Abbreviations: CYP2D6, cytochrome P450 2D6; EM, extensive metabolizer; GSTs, glutathioneS-transferases; GSTM1, glutathioneS-transferase M1; NATs,N-acetyltransferases; NAT2,N-acetyltransferase 2; PM, poor metabolizer.
2 To whom correspondence should be addressed. Email: mlemos{at}cygnus.ci.uc.pt
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