Document Detail


The association of a distinctive allele of NAD(P)H:quinone oxidoreductase with pediatric acute lymphoblastic leukemias with MLL fusion genes in Japan.
MedLine Citation:
PMID:  16266898     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVES: The enzyme NAD(P)H:quinone oxidoreductase (NQO1) detoxifies chemicals with quinone rings including benzene metabolites and flavonoids. Previous studies in Caucasian populations have provided evidence that a loss of function allele at nt 609 (C609T, Pro187Ser) is associated with increased risk of infant acute lymphoblastic leukemia (ALL) with MLL-AF4 fusion genes.
DESIGN AND METHODS: We genotyped 103 infants (<18 months) with ALL or acute myeloid leukemia (AML) in Japan and 185 controls for the frequency of allelic variation at nt 609 and 465 in NQO1 using standardized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology.
RESULTS: The C609T polymorphism is very common in Japan but we found no link with altered risk for infant ALL. However, a variant of another allele at nt 465 (C465T, Arg139Trp), also associated with diminished enzyme activity, was strongly associated (OR 6.36; CI 1.84-21.90; p=0.002) with infant ALL, especially in t(4;11)(q21;q23), MLL-AF4. No association was found between this allele and risk of infant AML with MLL gene fusions or infant ALL without MLL gene fusions. The same C465T allele has been linked recently, in an Oriental population, to sensitivity to benzene hematotoxicity.
INTERPRETATION AND CONCLUSIONS: These data endorse the notion that infant ALL with MLL fusion genes have a unique etiology possibly involving transplacental exposure to chemicals.
Authors:
Minenori Eguchi-Ishimae; Mariko Eguchi; Eiichi Ishii; Deborah Knight; Yujirou Sadakane; Keiichi Isoyama; Hiromasa Yabe; Shuki Mizutani; Mel Greaves
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Haematologica     Volume:  90     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-03     Completed Date:  2006-08-24     Revised Date:  2012-05-28    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  1511-5     Citation Subset:  IM    
Affiliation:
Section of Haemato-Oncology, Institute of Cancer Research, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Alleles*
Asian Continental Ancestry Group / genetics*
Gene Frequency / genetics
Genetic Variation / genetics
Humans
Infant
Infant, Newborn
Japan
Myeloid-Lymphoid Leukemia Protein / genetics*
NAD(P)H Dehydrogenase (Quinone) / genetics*
Oncogene Proteins, Fusion / genetics*
Polymorphism, Genetic
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Chemical
Reg. No./Substance:
0/MLL-AF4 fusion protein, human; 0/Oncogene Proteins, Fusion; 149025-06-9/Myeloid-Lymphoid Leukemia Protein; EC 1.6.5.2/NAD(P)H Dehydrogenase (Quinone); EC 1.6.5.2/NQO1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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