Source:http://linkedlifedata.com/resource/pubmed/id/21418106
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2011-5-18
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1600-0609
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pubmed:author | |
pubmed:copyrightInfo |
© 2011 John Wiley & Sons A/S.
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pubmed:issnType |
Electronic
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pubmed:volume |
86
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
477-83
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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
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pubmed:year |
2011
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pubmed:articleTitle |
The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia.
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pubmed:affiliation |
Pediatric Clinic II, The Juliane Marie Centre, The University Hospital Rigshospitalet, Copenhagen. louise.borst@rh.regionh.dk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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