Targeting the hallmarks of cancer: A nutritional epigenetics framework for prevention and intervention

Nearly 38% of cancer cases worldwide are attributable to modifiable risk factors. Emerging evidences suggest that nutrient-sensitive regulatory networks serve as molecular intermediaries connecting the exposome to cancer hallmark acquisition. Epigenetic plasticity positions diet as a modifiable determinant of cancer susceptibility, with phytochemicals, caloric restriction, and microbiome-derived metabolites modulating chromatin-modifying enzymes. However, context-dependent dual effects complicate nutritional intervention. We propose an integrative framework unifying modifiable risk factors, epigenetic regulation, and nutritional interventions within the Hallmarks of Cancer paradigm, repositioning nutrition as an upstream determinant of hallmark acquisition rather than an adjunctive consideration. This framework supports precision nutrition strategies in cancer prevention, though challenges in biomarker validation, accessibility, and patient adherence remain.