Vitamin D in Digestive Neoplasms: Molecular Mechanisms and Clinical Evidence

Digestive neoplasms represent a major global health burden, accounting for a substantial proportion of cancer incidence and mortality. Increasing attention has been directed toward modifiable factors that may influence both the onset and progression of these malignancies. Among them, vitamin D has emerged as a potential protective factor, with deficiency frequently associated with elevated risk and unfavorable prognosis in gastrointestinal cancers. This review critically examines the current evidence regarding the role of vitamin D and its receptor (VDR) in digestive tumorigenesis. Beyond its classical function in calcium and bone homeostasis, vitamin D exerts pleiotropic effects on cellular processes fundamental to carcinogenesis, including regulation of proliferation, differentiation, apoptosis, angiogenesis, immune modulation and genomic stability. Experimental studies demonstrate that adequate vitamin D status or administration of its analogues may suppress tumor growth and enhance responsiveness to conventional therapies. Epidemiological and clinical data, however, remain inconsistent across cancer subtypes, geographic populations and methods of vitamin D assessment. The analysis underscores the need for standardized evaluation of vitamin D levels, elucidation of dose–response relationships and clarification of interactions with genetic polymorphisms and environmental exposures. Future large-scale, randomized controlled trials are essential to establish causality and to define the optimal role of vitamin D in prevention and treatment strategies. Taken together, current findings support the hypothesis that vitamin D may serve not only as a biomarker of prognosis but also as a promising adjunctive approach in the management of digestive neoplasms.