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J BUON ; 21(6): 1459-1465, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28039708

RESUMO

PURPOSE: Polymorphic deletions in glutathione S-transferase (GST) genes are recognized as a risk factor for lymphoma, other hematological and non-hematological malignancies. The purpose of the present study was to investigate whether deletions of GSTT1 and GSTM1 as well as GSTP1 Ile- 105Val single nucleotide polymorphism influence clinical presentation, response to therapy and outcome in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The study included a total of 82 DLBCL patients treated with rituximab-CHOP (R-CHOP) therapy (6-8 cycles). GST genes were analyzed with PCR-based methodology. RESULTS: The obtained frequencies of GSTT1 and GSTM1 null genotypes were 24 and 63%, respectively. The variant GSTP1 Val allele was present in 76% of the patients. No association between GST genotypes and clinical presentation was found. However, a higher frequency of GSTM1 null genotype was observed in patients who developed DLBCL before the age of 60 [odds ratio (OR) 3.12, 95% confidence interval (CI) 1.11-9.17; p=0.03]. Patients carrying at least one GSTP1 Val allele achieved remission in a shorter time period than patients with GSTP1 Ile/Ile genotype (p=0.05). GST genotypes didn't influence the incidence of relapse and survival. There were no toxic effects, life-threatening infections or significant delay in immunochemotherapy in the analyzed group of patients. CONCLUSION: The present study showed the association of GSTM1 null genotype and DLBCL development before the age of 60 (prognostic cutoff). GST genotypes didn't influence survival, but patients with at least one low-producing GSTP1 Val allele achieved clinical remission in a shorter time period.


Assuntos
Biomarcadores Tumorais/genética , Deleção de Genes , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Linfoma Difuso de Grandes Células B/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/enzimologia , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Farmacogenética , Fenótipo , Modelos de Riscos Proporcionais , Fatores de Risco , Sérvia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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