Microplastic-Mediated Gene Expression Alterations and Cancer Risk: Insights from Toxicogenomic Analysis

Micro- and nanoplastics (MNPs) are pervasive environmental contaminants that pose significant threats to ecosystems and the health of humans and other organisms. Increasing evidence indicates that MNP exposure can induce various biological disturbances, including cytotoxicity, chronic inflammation, endocrine disruption, oxidative stress, metabolic dysfunction, and cellular impairment. Many of these processes are closely associated with cancer initiation and progression. However, the molecular mechanisms underlying the relationship between MNP exposure and carcinogenesis remain unclear. This review summarizes the current evidence regarding MNP-associated alterations in gene expression and discusses their potential implications in cancer development and progression. We highlight the toxicogenomic insights derived from the Comparative Toxicogenomics Database (CTD), focusing on key microplastics, including polyethylene, polyethylene terephthalate, polystyrene, and polyvinyl chloride. Specifically, we discuss the chemical-gene interactions, disease associations, gene ontology annotations, pathway enrichment profiles, and chemical similarity networks linked to these polymers. Overall, the available toxicogenomic evidence implies that MNP exposure is associated with biological processes involved in oxidative stress responses, inflammatory signaling, immune dysregulation, metabolic alterations, and cell cycle control, all of which are implicated in carcinogenesis. Finally, we discuss the strengths and limitations of CTD-based toxicogenomic approaches and propose research directions to better understand the potential contribution of MNP exposure to cancer risk.