Pathway-based pharmacogenomics of gemcitabine pharmacokinetics in patients with solid tumors.
Pharmacogenomics
; 13(9): 1009-21, 2012 Jul.
Article
en En
| MEDLINE
| ID: mdl-22838949
ABSTRACT
AIM:
The aim of this study was to evaluate the association of gemcitabine pathway SNPs with detailed pharmacokinetic measures obtained from solid tumor patients receiving gemcitabine-based therapy. MATERIALS &METHODS:
SNPs within nine gemcitabine pathway genes, namely CDA, CMPK, DCK, DCTD, NT5C2, NT5C3, SLC28A1, SLC28A3 and SLC29A1 were analyzed for association with gemcitabine pharmacokinetics.RESULTS:
Significant association of gemcitabine clearance with SNPs in NT5C2 was identified. Clearance of 2´,2´-difluorodeoxyuridine, a gemcitabine metabolite was significantly predicted by CDA, SLC29A1 and NT5C2 SNPs. This study reports an association of formation clearance of 2´,2´-difluoro-2´-deoxycytidine triphosphate, an active form of gemcitabine with SNPs within uptake transporters SLC28A1, SLC28A3 and SLC29A1.CONCLUSION:
Genetic variation in gemcitabine pathway genes is associated with its pharmacokinetics and hence could influence gemcitabine response. Our study identified pharmacogenetic markers that could be further tested in larger patient cohorts and could open up opportunities to individualize therapy in solid tumor patients.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
5'-Nucleotidasa
/
Citidina Desaminasa
/
Tranportador Equilibrativo 1 de Nucleósido
/
Desoxicitidina
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Estudios de Asociación Genética
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Pharmacogenomics
Asunto de la revista:
FARMACOLOGIA
/
GENETICA MEDICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos