CALCIUM AND THE PREVENTION OF COLON-CANCER

Chemoprevention studies utilizing calcium have now progressed from bas ic measurements to clinical trials. Calcium's effects on epithelial ce lls have demonstrated decreased proliferation and induced cell differe ntiation with increasing levels of calcium in vitro, similar in vivo e ffects in rodent and human colon, and decreased carcinogen-induced col onic tumor formation in rodents. Current studies are attempting to inh ibit colonic adenoma formation in human subjects. Most but not all epi demiologic studies also link increased dietary calcium with a decrease d risk of colon cancer. In animal models, supplemental dietary calcium has decreased mammary epithelial cell hyperplasia and hyperproliferat ion and colonic cell hyperproliferation when the latter was induced by bile acids, fatty acids, and partial resection of the small intestine . Supplemental dietary calcium also decreased carcinogen-induced colon ic tumors in several rodent models. In normal mice, and in mice carryi ng a targeted ape gene mutation, we recently increased colonic polypoi d hyperplasias by a Western-style diet containing low calcium and vita min D. In human subjects at increased risk for colon cancer, oral calc ium supplementation significantly reduced colonic epithelial cell prol iferation in most of the studies, including four randomized clinical t rials. These studies have now progressed to short-term human clinical trials, including trials that measure the regrowth of transformed aden oma cells. Short-term adenoma-regrowth clinical trials, however, are l imited in their ability to measure whether chemopreventive agents inhi bit early genotoxic events, abnormal cellular metabolic activities inv olved in tumor promotion over many years, or the progression of adenom a cells to carcinoma. (C) 1995 Wiley-Liss, Inc.