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Pharmacogenet Genomics. 2014 Feb;24(2):129-32. doi: 10.1097/FPC.0000000000000023.

A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469.

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aDepartment of Medicine, The University of Chicago, Chicago, Illinois bDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA.


XK469 (NSC 697887) is a selective topoisomerase II β 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.

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