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

dc.contributor.authorLemos, MC
dc.contributor.authorCabrita, FJ
dc.contributor.authorSilva, HA
dc.contributor.authorVivan, M
dc.contributor.authorPlácido, F
dc.contributor.authorRegateiro, FJ
dc.date.accessioned2008-12-02T17:04:51Z
dc.date.available2008-12-02T17:04:51Z
dc.date.issued1999
dc.description.abstractXenobiotic-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.en
dc.identifier.citationCarcinogenesis. 1999 Jul;20(7):1225-9en
dc.identifier.urihttp://hdl.handle.net/10400.4/247
dc.language.isoengen
dc.publisherOxforden
dc.subjectNeoplasias Hematológicasen
dc.subjectPredisposição Genética para Doençaen
dc.subjectCitocromo P-450 CYP2D6en
dc.titleGenetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasiasen
dc.typejournal article
dspace.entity.typePublication
rcaap.rightsopenAccess
rcaap.typearticleen

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