P12.19.B TOXICITY AND MECHANISMS OF BISPHENOL A IN GLIOBLASTOMA: INSIGHTS FROM MENDELIAN RANDOMIZATION AND NETWORK TOXICOLOGY

Abstract BACKGROUND The increasing prevalence of environmental pollutants has raised concerns about their potential role in cancer development. This study aimed to elucidate the molecular mechanisms by which bisphenol A (BPA), a widely used industrial compound, may contribute to glioblastoma (GBM) pathogenesis. MATERIAL AND METHODS Mendelian randomization (MR) analysis was conducted to assess the causal relationship between BPA exposure and GBM risk. The BPA-associated GBM targets were identified by integrating the GBM-related targets, differential expressed genes from the GEO database, and BPArelated targets. Target protein interaction networks were constructed using STRING and Cytoscape, followed by GO and KEGG pathway enrichment analyses. The expression of hub genes in GBM was validated using the GEPIA and HPA databases. Molecular docking studies were performed using CB-Dock2 to evaluate BPA-binding affinity to proteins encoded by hub genes. RESULTS MR analysis revealed a significant causal association between BPA exposure and increased GBM risk (p = 0.046; OR = 1.38). A total of 34 BPA-associated GBM targets were identified, among which TP53, MMP2, and KDR emerged as hub genes. Enrichment analysis linked these genes to key oncogenic pathways. Expression validation confirmed their significant upregulation in GBM tissues. Molecular docking analysis further demonstrated strong binding interactions between BPA and these targets. CONCLUSION This study provides evidence supporting a causal link between BPA exposure and GBM risk, with TP53, MMP2, and KDR identified as critical mediators. These findings offer new insights into the contribution of environmental pollutants to GBM pathogenesis, highlighting potential molecular targets for further investigation.