Abstract
CYP2B6, CYP2C19, ABCC4, and SOD2 have been implicated in adverse drug reactions and survival after cyclophosphamide (CPA) treatment. 110 BMT patients who received high dose CPA treatment were genotyped for variants in these genes and the results were correlated with toxicity and relapse. CYP2B6 genotype significantly influenced overall toxicity suggesting active CYP2B6 alleles led to higher rates of overall toxicity. The p.R487C deficiency allele was significantly associated with a lower rate of overall toxicity and a higher rate of relapse. SOD2 rs4880 V16A polymorphism was associated with significantly less CPA-related overall toxicity and significantly lower relapse rates by Kaplan-Meier analysis although the SOD2 finding regarding relapse was not significant when evaluated by the cumulative incidence function.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Adolescent
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Adult
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Aryl Hydrocarbon Hydroxylases / genetics*
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Blood Transfusion* / methods
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Bone Marrow Transplantation* / methods
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Child
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Child, Preschool
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Cytochrome P-450 CYP2B6
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Cytochrome P-450 CYP2C19
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Female
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Gene Frequency
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Genetic Association Studies
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Genotype
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Humans
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Infant
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Leukemia / diagnosis
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Leukemia / genetics
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Leukemia / therapy*
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Male
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Middle Aged
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Multidrug Resistance-Associated Proteins / genetics*
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Oxidoreductases, N-Demethylating / genetics*
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Polymorphism, Single Nucleotide / physiology
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Prognosis
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Superoxide Dismutase / genetics*
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Transplantation, Homologous
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Treatment Outcome
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Young Adult
Substances
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ABCC4 protein, human
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Multidrug Resistance-Associated Proteins
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Aryl Hydrocarbon Hydroxylases
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CYP2B6 protein, human
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CYP2C19 protein, human
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Cytochrome P-450 CYP2B6
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Cytochrome P-450 CYP2C19
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Superoxide Dismutase
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superoxide dismutase 2
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Oxidoreductases, N-Demethylating