Molecular Genetics of Colorectal Cancer

Introduction

Cancer is a disorder of cellular growth and differentiation that is due to a loss of function of regulatory pathways and feedback loops. Colorectal cancer is an excellent example of this mechanism because access via colonoscopy to the spectrum of premalignant lesions in the colon and rectum allows demonstration and study of the process. Sporadic colorectal cancer arises from pre-existing benign lesions that begin small and gradually enlarge as they transition histologically and biologically toward cancer via an adenoma-carcinoma or a serrated polyp-carcinoma sequence. In 1988, Bert Vogelstein published a sequence of genetic abnormalities that appeared to correlate with the histologic adenoma to carcinoma sequence. Subsequent research has confirmed Vogelstein’s observations and has expanded knowledge and understanding of the genetics of colorectal carcinogenesis. It is now known that at least three different genetic mechanisms lead to colorectal cancer, producing cancers of different biology. Understanding the molecular genetics of colorectal neoplasia is important. Fostering an understanding of the molecular genetics of colorectal neoplasia is the purpose of this chapter.