Dietary modulation of colon cancer: Effects on intermediary metabolism, mucosal cell differentiation, and inflammation

We review the profound effects that components of diets commonly consumed in western societies and linked through population studies to risk for colon cancer have on the development of intestinal cancer in humans and in mouse models. Focus is particularly on levels of vitamin D, interactive with calcium and fat, in establishing probability of tumor development even in mouse genetic models in which there is high penetrance of the disease. These dietary factors have also been used to develop a mouse model of dietary-induced sporadic colon cancer which exhibits similar lag, incidence, and frequency of tumor development, and relative incidence of carcinomas and adenomas, as seen for >90% of colon tumors that arise in the general population later in life. Potential mechanisms influenced by diet that alter probability of tumor development are outlined, including altered patterns of intermediary metabolism, differentiation, and inflammation in the intestinal mucosa, all apparent in the histopathologically normal intestinal mucosa well before neoplastic changes become detectable. This includes pathways by which macrophages signal to intestinal epithelial cells, revealing a new paradigm for how vitamin D may influence tumor development.