Intermediate biomarkers of increased risk for colorectal cancer: comparison of different methods of analysis and modifications by chemopreventive interventions.

Intermediate biomarkers of abnormal cell growth and development have recently been used in chemoprevention trials in attempts to identify the efficacy of chemopreventive agents in human subjects. Measurements carried out include those related to cell proliferation, differentiation, and gene structure and expression in the colon. Among modified patterns of cell proliferation identified by microautoradiographic or immunoperoxidase assays, a characteristic expansion in the size of the proliferative compartment has been observed in normal-appearing colorectal mucosa of human subjects with disease increasing cancer risk; the same patterns have been induced by chemical carcinogens in rodents. Moreover, this intermediate biomarker has been modulated by chemopreventive agents in both rodents and humans. Newer intermediate biomarkers being studied for application to human chemopreventive programs include normal and abnormal patterns of expression of mucins, intermediate filaments and cytoskeletal proteins, and the structure and expression of a variety of genes associated with normal and abnormal cell development. The application of these various intermediate biomarkers to chemoprevention studies is increasing the ability of investigators to analyze the effects of novel chemopreventive agents in the colon and in other organs.