Mycotoxin-induced DNA damage response and its association with carcinogenesis

Fungal species produce various secondary metabolites with carcinogenic and genotoxic properties, including aflatoxins, ochratoxins, fumonisins, sterigmatocystin, and griseofulvin. Acute or chronic exposure to these mycotoxins through contaminated food and feed can cause DNA damage, chromosomal instability, and epigenetic changes, ultimately leading to cancer. This review focuses on IARC-classified carcinogenic mycotoxins and their contribution to cancer development by disrupting the DNA damage response (DDR), thereby affecting apoptosis, cell cycle regulation, and genomic stability. Current knowledge of co-exposure to mycotoxins, host susceptibility, and validated biomarkers remains limited, particularly regarding the regulation of DDR genes. This necessitates more in-depth mechanistic and epidemiological research. Network analysis of host genes associated with mycotoxins in the CTD, integrated with DDR-related genes curated from CancerSEA, identified candidate DDR-associated genes implicated in pathways related to cell cycle regulation, DNA repair, oxidative stress response, and apoptosis. These findings represent database-derived associations and computational prioritization, rather than evidence of causal mechanistic roles in mycotoxin-induced carcinogenesis. Enrichment analysis using the Enrichr tool further identified the association between mycotoxin-associated DDR genes and cancer. In brief, this review enhances the understanding of the role of mycotoxins in DDR mechanisms and their potential contribution to cancer development, thereby providing a basis for improved molecular and translational approaches to address the associated health risks.