Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements
Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements
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DOI：
10.1038/sj.leu.2403613
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发表时间：
2005-02
期刊：
影响因子：
11.4
通讯作者：
M. Lanciotti;Carlo Dufour;L. Corral;P. D. Michele;Simona Pigullo;G. Rossi;Giuseppe Basso;A. Leszl;Matteo Luciani;L. L. Nigro-L.;C. Micalizzi;M. Valsecchi;A. Biondi;Riccardo Haupt
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文献类型：
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作者：
M. Lanciotti;Carlo Dufour;L. Corral;P. D. Michele;Simona Pigullo;G. Rossi;Giuseppe Basso;A. Leszl;Matteo Luciani;L. L. Nigro-L.;C. Micalizzi;M. Valsecchi;A. Biondi;Riccardo Haupt
NAD（P）H：醌氧化还原酶1（NQO 1）是一种解毒酶，可保护细胞免受氧化应激和有毒醌类的侵害。该基因的多态性（C609 T）在杂合子个体（C/T）中产生NQO 1蛋白活性的降低，而在变异等位基因纯合子个体（T/T）中产生NQO 1蛋白活性的消除。为了评估NQO 1失活多态性（CT/TT）是否是婴儿急性淋巴细胞白血病（iALL）的可能危险因素，我们调查了50例iALL患者的NQO 1基因型分布，其中32例MLL基因重排（MLL+），18例无MLL-。作为对照，106例儿童ALL（pALL）和147例健康受试者也进行了研究。与正常对照组相比，iALL MLL-1中低/无效活性NQO 1基因型的频率显著较高。（72% vs 38%，P= 0.006;比值比（OR）4.22，95%置信区间（CI）1.43-12.49），而iALL MLL+患者中未观察到差异（44 vs 38%，P= 0.553; OR 1.26，95% CI 0.58-2.74）。当pALL用作对照时，观察到类似的结果。我们的研究结果表明，只有没有MLL重排的iALL患者有一个显着较高的频率与低/空活性酶的NQO 1基因型，这表明NQO 1基因作为一个MLL独立的风险因素，在白血病的过程中，这种亚型的iALL。
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.