A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469.
Pharmacogenet Genomics
; 24(2): 129-32, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24300566
ABSTRACT
XK469 (NSC 697887) is a selective topoisomerase II ß inhibitor eliminated mainly by aldehyde oxidase I (AOX1). We performed a candidate gene study to investigate whether AOX1 genetic variation contributes to interindividual variability in XK469 clearance. Forty-one AOX1 single nucleotide polymorphisms (SNPs) and seven liver expression quantitative trait loci were genotyped in White patients with advanced refractory solid tumors (n=59) and leukemia (n=33). We found a significant decrease in clearance (τ=-0.32, P=0.003) in solid tumor patients with rs10931910, although it failed to replicate in the leukemia cohort (τ=0.18, P=0.20). Four other AOX1 SNPs were associated with clearance (P=0.01-0.02) in only one of the two cohorts. Our study provides a starting point for future investigations on the functionality of AOX1 SNPs. However, variability in XK469 clearance cannot be attributed to polymorphisms in AOX1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinoxalinas
/
Aldeído Oxidase
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Fígado
/
Neoplasias
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Antineoplásicos
Tipo de estudo:
Etiology_studies
/
Incidence_studies
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Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article