Pharmacogenetics of ABCB5, ABCC5 and RLIP76 and doxorubicin pharmacokinetics in Asian breast cancer patients
| Autor: | Suman Lal, P.C.S. Ang, Balram Chowbay, L. L Ooi, Z. W. Wong, Natalia Sutiman, N S Wong |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
0301 basic medicine ATP Binding Cassette Transporter Subfamily B Genotype Breast Neoplasms Locus (genetics) Pharmacology Biology 03 medical and health sciences 0302 clinical medicine Breast cancer Asian People Gene Frequency Pharmacokinetics Genetics medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Allele Allele frequency Alleles Genetic Association Studies Aged Antibiotics Antineoplastic Polymorphism Genetic GTPase-Activating Proteins Haplotype Exons Middle Aged medicine.disease 030104 developmental biology Haplotypes Doxorubicin Pharmacogenetics 030220 oncology & carcinogenesis Molecular Medicine ATP-Binding Cassette Transporters Female Multidrug Resistance-Associated Proteins |
| Zdroj: | The Pharmacogenomics Journal. 17:337-343 |
| ISSN: | 1473-1150 1470-269X |
| DOI: | 10.1038/tpj.2016.17 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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