Influence of dietary calcium and vitamin D on diet-induced epithelial cellhyperproliferation in mice

Background: Previous epidemiologic and laboratory studies, including some f rom our own laboratory, have suggested that a high-fat diet increases risk of cancer development in the pancreas, prostate, colon, and breast and that carcinogenesis in some of these organs may be influenced by alterations in dietary calcium and vitamin D, In this study, we sought to investigate the effect of added dietary calcium or vitamin D on the development of epithel ial cell hyperproliferation induced by a Western-style diet in the exocrine pancreas, prostate, and mammary gland of mice. Methods: Four-meek-old C57B L/65 mice were given either a control diet (American Institute of Nutrition [AIN]-76A), a Western-style diet (containing reduced calcium and vitamin D and the fat level of the average human Western diet), or a putative chemop reventive diet (a Western-style diet with the addition of dietary calcium a nd vitamin D), Nine weeks after dietary intervention, osmotic pumps were im planted in the mice to provide 3 days of bromodeoxyuridine (BrdU) infusion. All P values are two-sided. Results: Mice on the Western-style diet had st atistically significant increases in BrdU-labeling indices of epithelial ce lls in the interlobular (P = .015) and intralobular (P = .012) ducts and ce ntroacinar cells (P = .001) of the pancreatic duct system, the dorsal lobe of the prostate (P = .045), and the terminal ducts of the mammary gland (P = .032), compared with mice in the respective control diet groups. Adding d ietary calcium and vitamin D markedly suppressed the Western-style diet-ind uced hyperproliferation of epithelial cells in those tissues (P = .001-.033 ). Conclusions: This study confirms previous findings that a Western-style diet produces hyperproliferation of epithelial cells in several organs and that the changes can be prevented by increasing dietary calcium and vitamin D alone.