Association Of A Polymorphism Rs4946936 In FOXO3a 3'UTR With An Increased Risk Of Childhood Acute Lymphoblastic Leukemia In A Chinese Population

Background/Aims: FOXO3 a is an essential tumor suppressor that regulates the mechanisms of tumorigenesis and leukemogenesis.FOXO3 a polymorphisms have not been reported previously associated with an increased risk for childhood acute lymphoblastic leukemia(ALL).In this study,the rs4946936 polymorphism located in the3'UTR of FOXO3 a was selected to evaluate its relationship with a risk for ALL in Chinese children.Methods: Questionnaires,SNaPshot genotyping,real-time PCR,cell transfection and dual luciferase reporter assays were used in this study.Results: Parental alcohol consumption and whether the child's house had been painted had significantly different distributions among the cases and controls.In addition,the C to T mutation was significantly associated with the risk for ALL.We determined that FOXO3 a expression levels in patients with the CT or TT genotype were significantly higher than those of patients with the CC genotype.The T allele significantly increased the expression levels in luciferase assays and affected the binding affinity of miR-223 to the FOXO3 a 3'UTR.Conclusion: Rs4946936 in FOXO3 a was highly associated with an increased risk of childhood ALL in a Chinese population.