Early
cancer chemoprevention clinical trials in human subjects had to be carried out with large numbers of subjects studied for long durations, measuring
cancer as an end point. However new findings on abnormal epithelial cell growth and development during the multistage evolution of colonic
tumors made it possible to carry out
chemoprevention clinical trials in several stages, with fewer subjects studied for shorter durations, thus enabling investigators to analyze increasing numbers of chemopreventive agents and nutritional regimens in clinical trials. Supplemental
dietary calcium was the first candidate chemopreventive agent studied in this multistage approach in human subjects, as a putative agent for
colon cancer prevention. Early- and late-stage intermediate
biomarker studies in humans have strongly suggested utility for supplemental
dietary calcium to inhibit the development of benign and subsequent malignant
colonic neoplasms. Preclinical experimental studies have further demonstrated the ability of increased
dietary calcium to inhibit the evolution of colonic
tumors when they were induced by targeted mutations, dietary factors, and particularly when given over a long duration of lifespan.