Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-5-18
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1600-0609
pubmed:author
pubmed:copyrightInfo
© 2011 John Wiley & Sons A/S.
pubmed:issnType
Electronic
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
477-83
pubmed:meshHeading
pubmed-meshheading:21418106-Adolescent, pubmed-meshheading:21418106-Alleles, pubmed-meshheading:21418106-Base Sequence, pubmed-meshheading:21418106-Case-Control Studies, pubmed-meshheading:21418106-Child, pubmed-meshheading:21418106-Child, Preschool, pubmed-meshheading:21418106-Cytochrome P-450 CYP3A, pubmed-meshheading:21418106-DNA Primers, pubmed-meshheading:21418106-Denmark, pubmed-meshheading:21418106-Disease-Free Survival, pubmed-meshheading:21418106-Female, pubmed-meshheading:21418106-Gene Frequency, pubmed-meshheading:21418106-Genetic Predisposition to Disease, pubmed-meshheading:21418106-Humans, pubmed-meshheading:21418106-Infant, pubmed-meshheading:21418106-Male, pubmed-meshheading:21418106-Pharmacogenetics, pubmed-meshheading:21418106-Polymorphism, Single Nucleotide, pubmed-meshheading:21418106-Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:21418106-Precursor Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:21418106-Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:21418106-Prognosis, pubmed-meshheading:21418106-Risk Factors, pubmed-meshheading:21418106-Treatment Outcome
pubmed:year
2011
pubmed:articleTitle
The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia.
pubmed:affiliation
Pediatric Clinic II, The Juliane Marie Centre, The University Hospital Rigshospitalet, Copenhagen. louise.borst@rh.regionh.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't