Chemoprevention of colorectal cancer: problems, progress, and prospects.

Chemoprevention holds great promise as a complement to traditional CRC screening and treatment. Effective chemopreventive agents might improve patient outcomes by reducing the number of missed lesions, the morbidity associated with their identification and treatment, and their malignant potential. In addition, chemoprevention may reduce neoplastic potential simultaneously in several organs and improve clinical outcomes for persons at risk for cancers at multiple sites (e.g., colorectal and extracolonic cancers in HNPCC cohorts). Complex molecular circuits underlie the disease mosaic that is associated with aging. Several of these diseases share common mechanisms against which preventive interventions appear to be effective, such as NSAIDs for colorectal neoplasia and neurodegenerative disease, and statins for cardiovascular disease and colorectal neoplasia. Understanding these mechanisms and effects could raise prevention science to an entirely new level. The number of trials that are investigating chemopreventives against CR neoplasia is relatively small; if these agents live up to a fraction of their promise, the public health impact may be great (see Table 6).