Risk factors for colon neoplasia--epidemiology and biology.

Epidemiological, physiological and molecular models of colon carcinogenesis have been proposed. Consistent epidemiological risk factors include reduced plant-food intake (increased risk); elevated meat intake (increased risk); higher physical activity (reduced risk); and increased alcohol intake (increased risk). At the physiological level, these lifestyle variables may trigger processes that provide explanations for the associations: higher meat, fat and alcohol means more heterocyclic amines and higher levels of bile acids; higher plant food means higher intake of several anticarcinogens and fibre fermentation that produces volatile fatty acids; exercise has a variety of beneficial effects. This complexity is elaborated further in the context of the colonic milieu where interactions among digesta, bacteria and epithelial cells occur. The long-term likelihood of cancer is the summation of moment-to-moment changes in the colonic milieu brought about by this interaction. Possible relationships between established epidemiological risk factors, genetic susceptibility and somatic genetic changes are outlined.