Polyp Genetics.

The genetic events involved in the transformation of normal colonic epithelium to neoplastic polyps to invasive carcinoma, as initially proposed by Fearon and Vogelstein, form the foundation of our understanding of colorectal cancer. The identification of the polyp as the precursor lesion to colorectal cancer is the basis of many of our current practices for screening, surveillance, and prevention. The last three decades have seen a veritable explosion in our understanding of the molecular events involved in the pathogenesis of colorectal cancer. It is now clear that there are multiple genetic pathways in the polyp to carcinoma sequence. Some polyps previously thought to be nonneoplastic have now been shown to have malignant potential. Finally, increased understanding of the sequence of genetic events has led to the development of targeted therapeutics. The clinical translation of these scientific advances has made a significant impact on the management of patients with colorectal cancer. Accordingly, it is imperative that all clinicians caring for these patients have an understanding of the genetics of colorectal polyps and cancer. In this article, we review the etiology and genetic pathways to carcinoma associated with a range of polyps of the colon and rectum.