Nutrigenomics and Epigenetic Regulation in Cancer Prevention: Molecular Mechanisms, Dietary Bioactives, and Translational Perspectives

Cancer development is influenced not only by genetic alterations but also by epigenetic dysregulation driven by environmental and lifestyle factors, particularly diet. Nutrigenomics investigates how dietary components interact with the genome to influence gene expression, while nutritional epigenetics focuses on diet-induced modifications such as DNA methylation, histone modifications and non-coding RNA regulation. Increasing evidence indicates that bioactive dietary compounds can modulate epigenetic mechanisms involved in carcinogenesis, highlighting their potential role in cancer prevention. This narrative review synthesizes recent evidence, with emphasis on literature published between 2015 and 2025 and an updated search through September 2026 on the molecular interplay between diet, epigenetic regulation and cancer risk. We examine how key dietary factors—including methyl donors involved in one-carbon metabolism, polyphenols, short-chain fatty acids and omega-3 fatty acids—modulate epigenetic regulators such as DNA methyltransferases and histone deacetylases. Particular emphasis is placed on the emerging Nutrigenomics–Microbiome–Epigenome Axis, whereby microbiota-derived metabolites influence host chromatin architecture and gene expression pathways relevant to tumor suppression and inflammation. In addition, we discuss current evidence linking dietary patterns, including Mediterranean and Western diets, with distinct epigenomic signatures associated with cancer susceptibility. The review further explores the potential of epigenetic biomarkers and epigenome-wide association studies to support precision nutrition strategies for cancer prevention. Collectively, accumulating evidence suggests that diet-driven epigenetic plasticity may contribute to cancer prevention. However, the human evidence remains heterogeneous, and large, well-designed intervention studies with standardized epigenetic endpoints are required before mechanistic findings can be translated into clinically actionable precision nutrition strategies.