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The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia
Author(s) -
Borst Louise,
Wallerek Sandra,
Dalhoff Kim,
Rasmussen Kirsten K.,
Wesenberg Finn,
Wehner Peder S.,
Schmiegelow Kjeld
Publication year - 2011
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2011.01608.x
Subject(s) - odds ratio , hazard ratio , genotype , allele , medicine , cyp3a5 , childhood leukemia , oncology , etiology , single nucleotide polymorphism , leukemia , immunology , confidence interval , genetics , lymphoblastic leukemia , biology , gene
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.