Sirma Sema, Agaoglu Leyla, Yildiz Inci, Cayli Dilara, Horgusluoglu Emrin, Anak Sema, Yuksel Lebriz, Unuvar Aysegul, Celkan Tiraje, Apak Hilmi, Karakas Zeynep, Devecioglu Omer, Ozbek Ugur
Department of Genetics, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
Pediatr Blood Cancer. 2004 Oct;43(5):568-70. doi: 10.1002/pbc.20098.
NAD(P)H:quinone oxidoreductase1 (NQO1) is a two-electron reductase that detoxifies quinones derived from the oxidation of phenolic metabolites of benzene. Exposure to benzene metabolites increases the risk of hematotoxicity and leukemia. NQO1 enzyme activity protects the cells against metabolites of benzene. C to T base substitution at nucleotide 609 of NQO1 cDNA (C609T) results in loss of enzyme activity. Low NQO1 activity may play a role in etiology of acute leukemia.
We analyzed NQO1 C609T gene polymorphism using the PCR-RFLP method in 273 patients with de novo acute leukemia (189 acute lymphoblastic leukemia (ALL), and 84 acute myeloid leukemia (AML) and 286 healthy volunteers to investigate the role of NQO1 polymorphism in the etiology of acute leukemia.
The frequency of homozygosity for NOQ1 C609T polymorphism was 3.5% in the healthy control population and 2.5% in pediatric acute leukemia. The NQO1 C609T allele frequency was not statistically different in the children with acute leukemia in comparison to the controls (odds ratio (OR), 0.76; 95% confidence interval (CI), 0.58-1.01; P = 0.06). The distribution of NQO1 genotypes among children with acute leukemia was not statistically different from the control group (P = 0.13). These findings do not support the role of NQO1 C609T polymorphism in the etiology of de novo pediatric acute leukemia.
NAD(P)H:醌氧化还原酶1(NQO1)是一种双电子还原酶,可将苯的酚类代谢产物氧化产生的醌解毒。接触苯代谢产物会增加血液毒性和白血病的风险。NQO1酶活性可保护细胞免受苯代谢产物的影响。NQO1 cDNA第609位核苷酸的C到T碱基替换(C609T)导致酶活性丧失。低NQO1活性可能在急性白血病的病因中起作用。
我们采用PCR-RFLP方法分析了273例初发急性白血病患者(189例急性淋巴细胞白血病(ALL)和84例急性髓细胞白血病(AML))及286名健康志愿者的NQO1 C609T基因多态性,以探讨NQO1多态性在急性白血病病因中的作用。
健康对照人群中NQO1 C609T多态性纯合子频率为3.5%,儿童急性白血病患者中为2.5%。与对照组相比,急性白血病患儿的NQO1 C609T等位基因频率无统计学差异(优势比(OR)为0.76;95%置信区间(CI)为0.58-1.01;P = 0.06)。急性白血病患儿中NQO1基因型的分布与对照组无统计学差异(P = 0.13)。这些发现不支持NQO1 C609T多态性在初发儿童急性白血病病因中的作用。