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Region Hovedstaden - en del af Københavns Universitetshospital
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The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

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Objectives:  Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites and toxic substances, including chemotherapeutic agents. The aim of this study was to investigate the role of a single-nucleotide polymorphism (CYP3A5*3 6986A>G), which renders low enzyme activity, in the risk of developing ALL and in the outcome for children with ALL. Patients and methods:  Six hundred and sixteen childhood patients with ALL and 203 controls were genotyped by allelic discrimination. Results:  Individuals with the A allele had a 64% increased risk of developing childhood ALL (odds ratio = 1.64; 95% CI, 1.009-2.657). In general, event-free survival (EFS) did not differ in relation to CYP3A5 genotype. However, for patients with T-ALL, presence of the A allele was associated with better prognosis (EFS = 94.1%), while patients with the low-activity GG genotype only had an EFS of 61.5% (P = 0.015). Thus, for patients with T-ALL having no A allele and therefore low expression of CYP3A5, the risk of experiencing an event was almost eight times higher compared to those having at least one A allele (P = 0.045, hazard ratio = 7.749; 95% CI, 1.044-57.52). Conclusions:  This study shows that genetics may play a role in the risk of developing childhood ALL and indicates that improved treatment stratification of childhood patients with ALL may require addition of host genetic information.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Haematology
Vol/bind86
Udgave nummer6
Sider (fra-til)477-83
Antal sider7
ISSN0902-4441
DOI
StatusUdgivet - 2011

ID: 34568121