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  • Title: The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia.
    Author: Borst L, Wallerek S, Dalhoff K, Rasmussen KK, Wesenberg F, Wehner PS, Schmiegelow K.
    Journal: Eur J Haematol; 2011 Jun; 86(6):477-83. PubMed ID: 21418106.
    Abstract:
    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.
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