LncRNAs at the Crossroads of Precision Nutrition and Cancer Chemoprevention

Cancer remains a leading cause of morbidity and mortality worldwide, and effective strategies for cancer prevention are urgently needed to complement therapeutic ad-vances. While dietary factors are known to influence cancer risk, the molecular mecha-nisms that mediate inter-individual responses to nutritional exposures remain poorly defined. Emerging evidence identifies long non-coding RNAs (lncRNAs) as pivotal regulators of gene expression, chromatin organization, metabolic homeostasis, immune signaling, and cellular stress responses, core processes that drive cancer initiation and progression and are highly sensitive to nutritional status. In parallel, advances in pre-cision nutrition have highlighted how variability in genetics, metabolism, microbiome composition, and epigenetic landscapes shapes dietary influences on cancer susceptibility. This review integrates these rapidly evolving fields by positioning lncRNAs as molecular conduits that translate dietary exposures into transcriptional and epigenetic programs governing cancer development, progression, and therapeutic vulnerability. We provide mechanistic evidence demonstrating how dietary bioactive compounds and micronu-trients, including polyphenols (curcumin, resveratrol, EGCG), flavonoids, alkaloids such as berberine, omega-3 fatty acids, folate, vitamin D, probiotic metabolites (such as bu-tyrate and propionate), and trace elements (such as selenium, and zinc), modulate on-cogenic and tumor-suppressive lncRNAs. These nutrient-lncRNA interactions influence cancer-relevant pathways controlling proliferation, epithelial-mesenchymal transition, inflammation, oxidative stress, and metabolic rewiring. We further discuss emerging lncRNA signatures that reflect nutritional and metabolic states, their potential utility as biomarkers for individualized dietary interventions, and their integration into liquid biopsy platforms. Leveraging multi-omics datasets and systems biology, we outline AI-driven frameworks to map nutrient-lncRNA regulatory networks and identify tar-getable nodes for cancer chemoprevention. Finally, we address translational challenges, including compound bioavailability, inter-individual variability, and limited clinical validation, and propose future directions for incorporating lncRNA profiling into preci-sion nutrition-guided cancer prevention trials. Together, these insights position lncRNAs at the nexus of diet and cancer biology and establish a foundation for mechanistically informed precision nutrition strategies in cancer chemoprevention.