Ambient aromatic hydrocarbons and prostate cancer: mechanistic evidence linking benzene and PAH exposure to tumor progression
TL;DR
Current evidence supports a biologically plausible framework in which AH exposure may contribute to PCa initiation and progression and may intersect with pathways implicated in therapy resistance, although causal inference remains constrained by exposure misclassification, mixture complexity, and limited longitudinal biomarker data.
Abstract
Prostate cancer (PCa) remains one of the most common malignancies in men worldwide, yet modifiable environmental contributors remain incompletely defined. Aromatic hydrocarbons (AHs), particularly benzene and polycyclic aromatic hydrocarbons (PAHs), are widespread pollutants in ambient air, occupational settings, tobacco smoke, and high-temperature cooking emissions. In this review, we synthesize evidence from population-based and occupational epidemiology, dietary exposure proxies, animal carcinogenesis models, organoid systems, and cell-based mechanistic studies to assess the biological plausibility of AH-related prostate carcinogenesis. Human studies support modest but recurrent associations between long-term exposure to traffic-related mixtures, benzene-containing emissions, PAH-generating cooking practices, and increased PCa risk, with stronger duration–response signals in occupational settings. Experimental evidence further indicates that benzo[a]pyrene and related PAHs can induce prostatic mutagenesis, oxidative and genotoxic stress, endocrine perturbation, epigenetic remodeling, and immunosuppressive changes in the tumor microenvironment. The most coherent mechanisms involve AhR–AR crosstalk, CYP1A1/1B1-mediated bioactivation, ROS generation, DNA-adduct formation, DNMT1/HDAC6-associated epigenetic regulation, JAK2/STAT3-linked survival signaling, epithelial–mesenchymal transition, and IDO/TDO–kynurenine–AhR-mediated immune suppression. Collectively, current evidence supports a biologically plausible framework in which AH exposure may contribute to PCa initiation and progression and may intersect with pathways implicated in therapy resistance, although causal inference remains constrained by exposure misclassification, mixture complexity, and limited longitudinal biomarker data. Future studies should integrate precise exposure assessment with prostate-specific molecular studies, organoid systems, animal models, and prospective human cohorts.