The multistep model of colorectal carcinogenesis

Over the past decade, dramatic advances have been made in our understanding of the molecular biology of colorectal cancer. Based initially on detection of accumulating genetic abnormalities as normal colonocytes progress through the adenoma to carcinoma sequence, these observations have been refined to describe in considerable detail the molecular consequences of specific mutations. This report summarizes the current model of multistep molecular carcinogenesis in the large intestine, and emphasizes the consequences of mutation of the APC (gatekeeper of colonic epithelial proliferation) and p53 (guardian of the genome) genes. Clinical applications of these laboratory advances are discussed in the areas of colorectal cancer screening, prognostication, and therapy.