Interference with the adenoma-carcinoma sequence.

Epidemiological, pathological, and genetic studies indicate that most colorectal cancers arise in benign neoplastic polyps (adenomas). The likelihood of malignant change increases with adenoma size and volume of villous tissue. Adenomas are monoclonal products of a single stem cell mutation. Acquired genetic mutations and chromosomal deletions that occur late in the polyp-cancer sequence have been well described, although the initiating events leading to micro-adenoma formation are still unknown. Both inherited and environmental factors are implicated. Although the evidence in support of the adenoma-carcinoma sequence is indirect, it is compelling. Chemoprevention trials have not yet identified effective methods of primary prevention. Colonoscopic resection of adenomas (secondary prevention) plus post-polypectomy surveillance markedly decreases the incidence of colorectal cancer.