Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements.
Leukemia
; 19(2): 214-6, 2005 Feb.
Article
em En
| MEDLINE
| ID: mdl-15618957
ABSTRACT
NAD(P)Hquinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.
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Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Fatores de Transcrição
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Proto-Oncogenes
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Rearranjo Gênico
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NAD(P)H Desidrogenase (Quinona)
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Proteínas de Ligação a DNA
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Leucemia-Linfoma Linfoblástico de Células Precursoras
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article