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Pharmacogenomics J ; 20(2): 213-219, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31624332

RESUMEN

Standard treatment for glioblastoma (GBM) patients is surgery and radiochemotherapy (RCT) with temozolomide (TMZ). TMZ is a substrate for ABCB1, a transmembrane drug transporter. It has been suggested that survival for GBM patients receiving TMZ is influenced by different single-nucleotide variants (SNV) of ABCB1. We therefore examined SNV:s of ABCB1, namely 1199G>A, 1236C>T, 2677G>T/A, and 3435C>T and correlated to survival for GBM patients receiving RCT. In a pilot cohort (97 patients) a significant correlation to survival was found for SNV 1199G>A, with median OS for variant G/G patients being 18.2 months versus 11.5 months for A/G (p = 0.012). We found no correlation to survival for the other SNV:s. We then expanded the cohort to 179 patients (expanded cohort) and also included a confirmatory cohort (49 patients) focusing on SNV 1199G>A. Median OS for G/G versus A/G plus A/A was 15.7 and 11.5 months, respectively (p = 0.085) for the expanded cohort and 13.8 versus 16.8 months (p = 0.19) for the confirmatory. In conclusion, in patients with GBM receiving RCT with TMZ, no correlation with survival was found for the SNV:s 1236C>T, 2677G>T/A, and 3435C>T of ABCB1. Although the SNV 1199G>A might have some impact, a clinically significant role could not be confirmed.


Asunto(s)
Neoplasias Encefálicas/genética , Quimioradioterapia/métodos , Glioblastoma/genética , Polimorfismo de Nucleótido Simple/genética , Temozolomida/administración & dosificación , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Estudios de Cohortes , Femenino , Variación Genética/genética , Glioblastoma/mortalidad , Glioblastoma/terapia , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Tasa de Supervivencia/tendencias , Suecia/epidemiología , Resultado del Tratamiento
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