title: Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements.
abstract: NAD(P)H:quinone 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.
authors.affiliation: Hematology Unit, Department of Pediatric Hemato-Oncology, G Gaslini Children's Hospital, Genova, Italy. marinalanciotti@ospedale-gaslini.ge.it
authors.forename: M
authors.initials: M
authors.lastname: Lanciotti
authors.forename: C
authors.initials: C
authors.lastname: Dufour
authors.forename: L
authors.initials: L
authors.lastname: Corral
authors.forename: P
authors.initials: P
authors.lastname: Di Michele
authors.forename: S
authors.initials: S
authors.lastname: Pigullo
authors.forename: G
authors.initials: G
authors.lastname: De Rossi
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: A
authors.initials: A
authors.lastname: Leszl
authors.forename: M
authors.initials: M
authors.lastname: Luciani
authors.forename: L
authors.initials: L
authors.lastname: Lo Nigro
authors.forename: C
authors.initials: C
authors.lastname: Micalizzi
authors.forename: M G
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: R
authors.initials: R
authors.lastname: Haupt
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015321:Gene Rearrangement; D005838:Genotype; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D051788:Myeloid-Lymphoid Leukemia Protein; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics*; D011519:Proto-Oncogenes / Q000235:genetics*; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D011495:Histone-Lysine N-Methyltransferase