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Pharmacogenetics of ABCB5, ABCC5 and RLIP76 and doxorubicin pharmacokinetics in Asian breast cancer patients.
Lal, S; Sutiman, N; Ooi, L L; Wong, Z W; Wong, N S; Ang, P C S; Chowbay, B.
Afiliación
  • Lal S; Laboratory of Clinical Pharmacology, Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore.
  • Sutiman N; Clinical Pharmacology, SingHealth, Singapore.
  • Ooi LL; Division of Surgical Oncology, National Cancer Center, Singapore.
  • Wong ZW; Division of Medical Oncology, National Cancer Center, Singapore.
  • Wong NS; Division of Medical Oncology, National Cancer Center, Singapore.
  • Ang PCS; Division of Medical Oncology, National Cancer Center, Singapore.
  • Chowbay B; Laboratory of Clinical Pharmacology, Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore.
Pharmacogenomics J ; 17(4): 337-343, 2017 07.
Article en En | MEDLINE | ID: mdl-26975227
This study investigated the impact of ABCB5, ABCC5 and RLIP76 polymorphisms on doxorubicin pharmacokinetics in Asian breast cancer patients (N=62). Direct sequencing was performed to screen for previously identified ABCC5 polymorphisms as well as polymorphisms in the exons and exon-intron boundaries of ABCB5 and RLIP76 genes. Genotype-phenotype correlations were analyzed using Mann-Whitney U-test. The homozygous variant allele at the ABCC5 g.+7161G>A (rs1533682) locus was significantly associated with higher doxorubicin clearance (g.+7161AA vs g.+7161GG, CL/BSA (Lh-1m-2): 30.34 (25.41-33.60) vs 22.46 (15.04-49.4), P=0.04). Homozygosity for the reference allele at the ABCC5 g.-1679T>A locus was associated with significantly higher doxorubicinol exposure (g.-1679TT vs g.-1679TA, AUC0-∞/dose/BSA (hm-5): 15.48 (6.18-67.17) vs 8.88 (3.68-21.71), P=0.0001). No significant influence of the three newly identified ABCB5 polymorphisms (c.2T>C, c.343A>G and c.1573G>A) on doxorubicin pharmacokinetics was observed. No polymorphisms were identified in the RLIP76 gene. These findings suggest that ABCC5 polymorphisms may explain partially the interpatient variability in doxorubicin disposition.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Doxorrubicina / Miembro 1 de la Subfamilia B de Casetes de Unión a ATP / Transportadoras de Casetes de Unión a ATP / Proteínas Activadoras de GTPasa / Proteínas Asociadas a Resistencia a Múltiples Medicamentos / Pueblo Asiatico Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Pharmacogenomics J Asunto de la revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Doxorrubicina / Miembro 1 de la Subfamilia B de Casetes de Unión a ATP / Transportadoras de Casetes de Unión a ATP / Proteínas Activadoras de GTPasa / Proteínas Asociadas a Resistencia a Múltiples Medicamentos / Pueblo Asiatico Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Pharmacogenomics J Asunto de la revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos