Single-Nucleotide Polymorphisms rs2253310 and rs4946936 in the forkhead box O3 Gene and Their Correlation with Prognosis in Glioblastoma

BACKGROUND: Glioblastoma is the most aggressive primary brain tumor characterized by poor prognosis and complex molecular alterations. Forkhead box O3 (FOXO3), a transcription factor involved in apoptosis, oxidative stress, and cell cycle regulation, has been implicated in cancer biology. This study aimed to evaluate the association of FOXO3 gene polymorphisms (rs2253310 and rs4946936) with glioblastoma susceptibility and clinical outcomes. MATERIALS AND METHODS: A prospective case-control study was conducted on 66 histologically confirmed glioblastoma patients and 66 healthy controls (n = 132). Genotyping of FOXO3 polymorphisms was performed using TaqMan allelic discrimination real-time polymerase chain reaction (PCR) assays. Clinical parameters were recorded. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier survival analysis and t-tests, with P < 0.05 considered statistically significant. RESULTS: No significant differences in genotype or allele frequencies of rs2253310 (P = 0.4771) and rs4946936 (P = 0.5308) were observed between cases and controls. Survival analysis revealed no significant association of either polymorphism with OS (rs2253310, P = 0.549; rs4946936, P = 0.356). However, the mutant genotypes demonstrated significantly longer PFS for both rs2253310 (mean PFS: 55.5 days, P = 0.022) and rs4946936 (P = 0.022), suggesting a potential protective role in delaying tumor progression. CONCLUSION: FOXO3 rs2253310 and rs4946936 polymorphisms are not significantly associated with glioblastoma susceptibility or OS. Nevertheless, the mutant genotypes correlate with improved PFS, highlighting their possible prognostic relevance. Larger, multicentric studies are warranted to validate these findings and explore the underlying biological mechanisms.