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Browsing by Author "Silva, HA"

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  • Genetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasias
    Publication . Lemos, MC; Cabrita, FJ; Silva, HA; Vivan, M; Plácido, F; Regateiro, FJ
    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.
    1999Journal article Open access Show more
  • Molecular detection of EGFRvIII-positive cells in the peripheral blood of breast cancer patients
    Publication . Silva, HA; Abraúl, E; Raimundo, D; Dias, MF; Marques, C; Guerra, C; Oliveira, CF; Regateiro, FJ;
    The aim of this study is to evaluate epidermal growth factor receptor variant III, EGFRvIII, a cancer specific mutant, as a possible marker for the diagnosis of breast cancer occult systemic disease. EGFRvIII mRNA was identified by an RT-nested PCR with a high sensitivity. In 102 women studied, the mutant was detected in the peripheral blood of 30% of 33 low risk, early stage patients, in 56% of 18 patients selected for neoadjuvant chemotherapy, in 63.6% of 11 patients with disseminated disease and 0% of 40 control women. In low risk, early stage patients, the presence of one or more tumour characteristics predicting recurrence such as the absence of oestrogen receptors and the presence of ERBB2 or histologic grades G2/G3 was significantly associated with EFGRvIII detection (p<0.05). EGFRvIII mRNA has characteristics to be a useful marker for the diagnosis of occult systemic disease in breast cancer. Follow-up studies will evaluate its clinical value as a decision criterion for systemic therapy.
    2006Journal article Open access Show more