Exposure to bisphenol analogues and advanced high-grade serous ovarian cancer survival: An integrative study combining epidemiology and mechanism exploration
The reproductive toxicity and potential carcinogenicity of bisphenol analogs (BPs) has drawn attention, but their role in ovarian cancer prognosis remains unclear. We aimed to explore the association between BPs and advanced high-grade serous ovarian cancer (HGSOC) survival. In the nested case-control study, 318 patients were included. Conditional logistic regression models estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Joint effects were assessed using quantile g-computation and Bayesian kernel machine regression. Targets were obtained from ChEMBL, Swiss Target Predict, STITCH, CTD, OMIM, and Gene-Cards databases, followed by pathway enrichment, molecular docking, and dynamic simulation analyses to explore potential interactions. Exposure to high BPS concentration was associated with worse advanced HGSOC survival (OR = 2.18, 95% CI: 1.01 - 4.71) when compared the highest tertile with the lowest. A dose-response relationship was also discovered between BPS (per SD increment) and decreased advanced HGSOC survival (OR = 1.36, 95% CI: 1.01 - 1.83). Core targets mainly enriched the tumorigenesis, hormone regulation, and cellular adaptation signaling pathways. EGFR and ESR1 exhibited the strongest binding affinities with BPS. High urinary BPs concentrations were associated with worse advanced HGSOC survival, potentially via interactions with EGFR and ESR1 influencing progression.