Bisphenol A and prostate cancer: from population exposure to context-dependent mechanisms and translational implications

Abstract

Bisphenol A (BPA) is a widespread endocrine-disrupting chemical with potential relevance to prostate cancer. This review provides a BPA-centered synthesis of evidence from human epidemiological studies, animal models, human prostate tissue and human-derived systems, and mechanistic investigations, while considering major BPA substitutes only where they inform substitution safety and class-informed assessment. Human studies provide limited and heterogeneous signals linking BPA exposure to prostate cancer incidence, prostate-specific antigen concentrations, and post-diagnosis outcomes, but causal inference is constrained by single-sample exposure assessment, cross-sectional or diagnosis-period designs, and heterogeneous endpoints. Experimental evidence supports a context-dependent model in which exposure timing, internal dose, hormonal milieu, androgen receptor status, cellular state, and subsequent biological challenge shape BPA-associated responses involving receptor signaling, epigenetic regulation, metabolism, redox homeostasis, and tissue organization. Rather than supporting uniform direct carcinogenicity, current evidence is more consistent with context-dependent modification of prostate biology, with distinct implications for cancer initiation, disease progression, hormone or treatment responsiveness, and biomarker alterations. These evidence domains should not be considered interchangeable. BPA measurements are not currently validated for prostate cancer screening, prognostic assessment, or treatment decisions. Progress will require repeated prospective biomonitoring, exposure-anchored human-relevant models, causal testing of proposed mediators, clinically verified outcomes, and targeted evaluation of major BPA substitutes such as bisphenol S (BPS) and bisphenol F (BPF), for which prostate-specific evidence remains comparatively limited.