Investigating the potential causal link between BPA and ovarian carcinogenesis: a network toxicology and mendelian randomization study on the CTRC/PRDX1/SKP1 pathway.

This study elucidates the association between Bisphenol A (BPA) exposure and ovarian cancer development, along with its underlying mechanisms. We employed a 'Toxicological Prediction-Causal Inference-Structural Validation' framework, integrating network toxicology and Mendelian Randomization (MR) analysis, enabling insights into BPA's carcinogenic effects. This approach used network toxicology to predict molecular targets of BPA in the ovary, MR to establish genetic evidence for the causal link, and molecular docking to validate structural basis of interaction with key pathways. Our findings indicate BPA may influence cellular processes, including homeostasis, stress, and cycle regulation, while activating PI3K/Akt signaling. Enrichment analysis revealed pathways associated with amoebic infection, suggesting interactions between infection status and chemical exposure. With evidence that emetine enhances cancer cell sensitivity, we hypothesize BPA may activate inflammation pathways shared with amoebic infection, particularly in predisposed individuals. Consequently, BPA might induce inflammatory microenvironment, thereby influencing progression and treatment response. This study identifies CTRC/PRDX1/SKP1 as crucial and proposes hypothesis of synergistic effects between exposure and infection history. These findings underscore incorporating environmental exposure into risk assessment, offering perspectives on carcinogenesis and avenues for prevention.