The adenoma-carcinoma sequence and prospects for the prevention of colorectal neoplasia.

Colorectal adenomatous polyps are thought to be precursors of colorectal cancer. This article reviews the evidence for the adenoma-carcinoma sequence and possible interventions in regard to the prevention of colorectal cancer. Although there is no direct evidence to support the adenoma-carcinoma sequence, there is considerable indirect evidence from a range of epidemiological, histopathological, and molecular genetic studies. Sigmoidoscopy and fecal occult blood testing may offer the potential for secondary prevention, but screening based on either of these methods in the general population has not yet been shown conclusively to be effective and efficient. Although the importance of dietary factors in the etiology of colorectal lesions suggests that there may be potential for primary prevention through dietary modification or nutrient supplementation, few trials have been completed to date. Although observational studies suggest that the incidence of colorectal cancer may be reduced by as much as 50% by the use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs), further research is needed to determine the effects of individual NSAIDs and the appropriate prophylactic dose and to develop new NSAIDs with reduced gastrointestinal side-effects. Other strategies for primary prevention could focus on interventions to increase physical activity levels, to encourage smoking cessation, and to moderate alcohol consumption. Potential areas for further research are proposed.