Molecular mechanisms of colorectal carcinogenesis
Colorectal cancer (CRC) presents in three major forms: inherited, sporadic, and familial. Although the mechanisms underlying familial CRC are poorly understood, a large body of evidence suggests that inherited and sporadic CRC are caused by sequential genetic and molecular events. There are three distinct pathways of CRC pathogenesis: the chromosomal instability pathway (CIN), the microsatellite instability pathway (MSI), and the serrated pathway. The majority of CRCs arise from the CIN pathway, which is characterized by defects in chromosomal segregation, telomere stability, and the DNA damage response. Microsatellite instability derives from the loss of DNA mismatch repair and is found in about 15 % of all CRCs, 3 % of which are associated with Lynch syndrome. The serrated pathway, recognized only in the last 15 years, describes the progression of serrated polyps to CRC. The goal of this chapter is to discuss the key genetic and molecular elements of each pathway from a historical perspective and to describe the relevance of this knowledge to the care of patients with CRC.
