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

Xenobiotic-metabolizing enzymes constitute an important line of defence aga inst 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 carcinogen esis. The aim of this study was to determine the existence of any associati on between the main genetic polymorphisms of cytochrome P450 2D6 (CYP2D6), glutathione S-transferase M1 (GSTM1) and N-acetyltransferase 2 (NAT2) and a n altered risk for haematological neoplasias, A total of 160 patients and 1 28 controls were genotyped by means of PCR-RFLP-based assays. Mutated allel es 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 leuka emia 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, An alysis of the GSTM1 and NAT2 polymorphisms failed to show an association wi th any of the neoplasias, although a near significant increase in fast acet ylators 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 increa sed risk for leukaemia, possibly by an increase in the metabolic activation of chemical carcinogens or linkage to another cancer-causing gene. Opposit e findings presented in other studies may reflect geographical differences in the type of environmental carcinogens to which different populations are exposed.