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Int J Hematol ; 108(3): 246-253, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29737460


Recent studies have shown that tumors of relapsed acute myeloid leukemia (AML) present additional genetic mutations compared to the primary tumors. The base excision repair (BER) pathway corrects oxidatively damaged mutagenic bases and plays an important role in maintaining genetic stability. The purpose of the present study was to investigate the relationship between BER functional polymorphisms and AML relapse. We focused on five major polymorphisms: OGG1 S326C, MUTYH Q324H, APE1 D148E, XRCC1 R194W, and XRCC1 R399Q. Ninety-four adults with AML who achieved first complete remission were recruited. Genotyping was performed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The OGG1 S326C CC genotype (associated with lower OGG1 activity) was observed more frequently in patients with AML relapse [28.9 vs. 8.9%, odds ratio (OR) = 4.10, 95% confidence interval (CI) = 1.35-12.70, P = 0.01]. Patients with the CC genotype exhibited shorter relapse-free survival (RFS). Moreover, the TCGA database suggested that low OGG1 expression in AML cells is associated with a higher frequency of mutations. The present findings suggest that the OGG1 S326C polymorphism increased the probability of AML relapse and may be useful as a prognostic factor for AML relapse risk.

ADN Glicosilasas/genética , Reparación del ADN/genética , Reparación del ADN/fisiología , Estudios de Asociación Genética , Genotipo , Leucemia Mieloide Aguda/genética , Mutación , Polimorfismo Genético , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Daño del ADN , Supervivencia sin Enfermedad , Femenino , Expresión Génica , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Especies Reactivas de Oxígeno , Recurrencia , Riesgo , Tasa de Supervivencia , Adulto Joven