Abstract
Gastrointestinal (GI) cancers, including colorectal, gastric, esophageal, pancreatic, and liver cancers, represent a significant global health burden, with high prevalence and mortality rates driven by aging, lifestyle factors, and infections. Emerging research highlights the role of vitamin D in cancer biology, particularly its potential in the prevention and management of GI cancers. Through its active form, calcitriol, vitamin D regulates cell proliferation, apoptosis, angiogenesis, and immune responses via the vitamin D receptor (VDR). Epidemiological studies suggest an inverse association between vitamin D deficiency and cancer risk, while experimental models demonstrate its anti-tumor effects. Additionally, vitamin D influences gut microbiota composition and immune regulation, potentially enhancing cancer immunity and response to immunotherapy. Despite promising evidence, clinical trials have yielded mixed results, underscoring the need for further research to determine optimal supplementation strategies, individual responses, and genetic influences. This review explores vitamin D's mechanisms, epidemiological evidence, and therapeutic potential in GI cancers, advocating for personalized approaches in cancer prevention and treatment.