Reducing the risk of colorectal cancer by intervening in the process of carcinogenesis: a status report.

Risk factors for colorectal cancer have been identified, and significant advances have been made in understanding the process of colorectal carcinogenesis. The transition from normal colonic mucosa to adenomatous polyp to adenocarcinoma is a gradual process involving genetic and epigenetic instability that can take decades, offering numerous opportunities for early detection (e.g., colonoscopy screenings), lifestyle changes (e.g., reduced red meat intake, increased physical activity, and reduced alcohol/ tobacco exposure), and chemopreventive interventions. Aspirin and various other nonsteroidal anti-inflammatory drugs may have chemopreventive benefits for colorectal cancer and other human epithelial carcinomas, butthe long-term use of nonsteroidal anti-inflammatory drugs is associated with serious gastrointestinal side effects. Recently, overexpression of cyclooxygenase-2 has been documented in colorectal tumors and numerous other pre-cancers and cancers. The development of selective cyclooxygenase-2 inhibitors, such as celecoxib, provides an opportunity for preventive intervention in the carcinogenic process. Celecoxib has been approved for the management of familial adenomatous polyposis and is under investigation for the management of sporadic colorectal polyps and for its potential as a chemopreventive agent for other cancers.