RESUMO
In this case report, we present genetic differences in two morphine-related gene sequences, UDP-glucuronosyltransferase 2B7 (UGT2B7) and mu opioid receptors (MOR1), in two cancer patients whose clinical responses to morphine were very different [i.e., sensitive (patient 1) and low responder (patient 2)]. In addition, allelic variants in the UGT2B7 gene were analyzed in 46 Japanese individuals. Amplified DNA fragments for the two genes of interest were screened using single strand conformation polymorphism and then sequenced. In the UGT2B7 gene, 12 single nucleotide polymorphisms (SNPs) were newly identified with an allelic frequency ranging from 0.022 to 0.978. Six SNPs in the promoter region (A-1302G, T-1295C, T-1111C, G-899A, A-327G, and T-125C) and two coding SNPs (UGT2B7*2 in exon 2 and C1059G in exon 4) appeared to be consistently linked. Remarkable differences in the nucleotide sequence of UGT2B7 were observed between the two patients; in contrast to patient 1 who had "reference" alleles at almost SNP positions, but a rare ATTGAT*2(AT)C haplotype as homozygosity, patient 2 was a homozygous carrier for the predominant GCCAGC*1(TC)G sequence. Serum morphine and two glucuronide concentrations in patient 2 suggest that the predominant GCCAGC*1G sequence was not associated with a "poor metabolizer" phenotype. In the MOR1 gene, patient 1 had no SNPs, whereas patient 2 was a heterozygous carrier for both the G-1784A and A118G alleles. The present study describes substantial differences in genotype patterns of two genes of interest between the two patients. The results necessitate larger trials to confirm these observations in larger case control studies.
Assuntos
Analgésicos Opioides/metabolismo , Glucuronosiltransferase/genética , Neoplasias Hipofaríngeas/genética , Morfina/metabolismo , Síndrome de Pancoast/genética , Receptores Opioides mu/genética , Idoso , Analgésicos Opioides/uso terapêutico , Fragmentação do DNA , Feminino , Variação Genética , Genótipo , Humanos , Neoplasias Hipofaríngeas/complicações , Masculino , Pessoa de Meia-Idade , Morfina/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Síndrome de Pancoast/complicações , Reação em Cadeia da Polimerase , Resultado do TratamentoRESUMO
Karyotyping and marker analysis of G- and C-banded metaphases from a metastatic bronchial carcinoma revealed a dominant stemline with five markers and four sidelines with additional markers. One to three minute bodies were noted in the majority of cells and these were classified as markers. On the basis of this analysis it was possible to postulate an evolutionary pathway within the tumour whereby the stemline was derived from existing sidelines.
