The Association of NAD(P)H:quinine Oxidoreductase Gene Polymorphisms With Pediatric Acute Lymphoblastic Leukemia

Abstract

Objectives: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme that protects cells against mutagenicity of free radicals and toxic oxygen metabolites. C to T base substitution at nucleotides 609 and 465 of NQO1 cDNA, results in loss of enzyme activity. Low NQO1 activity may play a role in etiology of ALL. In the present study, we investigated the association between the NQO1 polymorphisms and increased risk of ALL in children. Methods: C609T and C465T polymorphisms of NQO1 were explored using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay in 100 pediatric ALL patients and 135 healthy controls. Results: Although C609T polymorphism is very common among the Iranian population, we found no association between this variant and increased risk for pediatric ALL [odds ratio (OR) = 0.95; 95% confidence interval (95% CI) = 0.55–1.64]. Interestingly the other polymorphic allele of NQO1 (C465T) was strongly associated with pediatric ALL (OR = 7.83; 95% CI= 3.27-18.75). Conclusion: These findings do not support the predisposing role of NQO1 C609T polymorphism for pediatric ALL. However, The C465T polymorphism was associated with increased risk of pediatric ALL. Further studies with larger sample including evaluating multiple gene– gene interactions seem necessary to validate the exact role of these mutations.