Calcium, vitamin D, and colon cancer.
Calcium contributes to the progression of epithelial cells through all phases of the proliferative cycle and into stages of cell differentiation; intracellular concentrations of calcium that are required for cell renewal, however, are lower than those required for epithelial-cell differentiation. These effects of calcium are modulated by interactions with 1,25-dihydroxy-vitamin D3, phosphate, and fatty acids, all of which are partly dependent on dietary intake. In rodent models, increased dietary calcium inhibited hyperproliferation of colon epithelial cells induced by increased levels of fatty acids or bile acids present in the colon. When carcinogens induced hyperproliferation of colon epithelial cells the hyperproliferation was decreased by added dietary calcium, and in several animal models the occurrence of carcinogen-induced carcinomas of the colon decreased with increased dietary calcium. A nutritional stress diet, designed to represent human Western dietary intake of calcium, phosphate, vitamin D, and fat, produced hyperproliferation and hyperplasia in the colons of rodents; these effects were reduced by increasing dietary levels of calcium. Decreased levels of ornithine decarboxylase also were reported in human and rodent colon mucosa exposed to increasing levels of calcium. In human subjects at increased risk for familial colon cancer, hyperproliferation of colon epithelial cells was reduced after oral dietary supplementation with calcium. In epidemiological studies, several investigators reported inverse correlations between levels of dietary calcium intake and the incidence of colon cancer. Extrapolation of the data have suggested a protective effect of total calcium intakes above 1500 to 1800 mg/day.
Newmark
H L
HL
Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Lipkin
M
M
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D003840:Deoxycholic Acid / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004127:Dimethylhydrazines; D006801:Humans; D051379:Mice; D051381:Rats; D014807:Vitamin D / Q000008:administration & dosage
D002136:Calcium, Dietary; D002273:Carcinogens; D004127:Dimethylhydrazines; D003840:Deoxycholic Acid; D014807:Vitamin D; D019813:1,2-Dimethylhydrazine; D002118:Calcium