title: The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Pediatric Clinic II, The Juliane Marie Centre, The University Hospital Rigshospitalet, Copenhagen. louise.borst@rh.regionh.dk
authors.forename: Louise
authors.initials: L
authors.lastname: Borst
authors.forename: Sandra
authors.initials: S
authors.lastname: Wallerek
authors.forename: Kim
authors.initials: K
authors.lastname: Dalhoff
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Rasmussen
authors.forename: Finn
authors.initials: F
authors.lastname: Wesenberg
authors.forename: Peder S
authors.initials: PS
authors.lastname: Wehner
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
mesh_terms: D000293:Adolescent; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D003718:Denmark; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D017931:DNA Primers; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A