Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Genetic variations,
particularly gene polymorphisms, have been closely linked to increased susceptibility to ALL. One of those
genes is Forkhead box O3 (FOXO3), which is considered a potential tumor suppressor gene.
Aim: This study intended to examine the potential significance of the FOXO3 (rs17069665) single nucleotide
polymorphism (SNP) as a risk factor for childhood ALL, in addition to its effect on the laboratory results, clinical
manifestations and the clinical outcome after induction of chemotherapy.
Subjects and methods: Sixty-six newly diagnosed ALL children and 70 healthy children of matched age and sex as
controls were recruited. FOXO3 (rs17069665) polymorphism was detected using TaqMan real time PCR.
Results: Higher frequencies of the (AG) genotype and G-allele of FOXO3 (rs17069665) variant were present in
ALL patients in comparing with the controls (16.7 % vs. 4.3 %, p = 0.017 and 11.4 % vs. 2.1 %, p = 0.003,
respectively). The frequencies of the FOXO3 (rs17069665) SNP reflected a noticeably higher risk of ALL under
diverse genetic models, including the co-dominant model (AG vs. AA, OR = 2.55), dominant (AG + GG vs. AA,
OR = 2.81), and allelic (G-allele vs. A-allele, OR = 2.9) models. The single case of c-MYC mutation was observed
with the (GG) genotype. No significant association between FOXO3 (rs17069665) SNP polymorphism and
response to chemotherapy was found.
Conclusion: Our findings showed that the FOXO3 (rs17069665) polymorphism was associated with a greater
incidence of ALL in Egyptian children, which might be a potential biomarker for ALL susceptibility.