Dietary calcium and gastrointestinal cancer: risk or protection

Calcium is an essential inorganic element that acts as a crucial intracellular second messenger, regulating numerous cellular signaling pathways. Variations in calcium concentrations significantly influence a wide array of physiological and pathological processes. Nearly all human physiological activities are intricately linked to calcium signal regulation, with different cell types executing specific functions through distinct calcium signaling patterns. Dysregulation of calcium metabolism can lead to hypercalcemia or hypocalcemia, and hypercalcemia is often associated with various malignancies, where it facilitates cancer cell proliferation and metastasis, particularly in gastroesophageal and colorectal cancers. Conversely, studies indicate that dietary calcium and vitamin D supplements can reduce the risk of several cancers. In colorectal cancer, for instance, intracellular Ca²⁺ signaling can paradoxically promote both tumor initiation and progression, as well as induce tumor cell death. Similarly, in gastroesophageal carcinoma, specific calcium signals are critical for processes such as proliferation, migration, and invasion. This review elucidates the dual role of calcium signaling in gastrointestinal carcinomas, highlighting the paradox of its context-dependent, both promotive and protective, effects.