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Colorectal cancer is a major cause of cancer-related mortality in the United States and many other regions of the world. It is currently the second most common cause of cancer death in the United States for men and women combined (nearly 150,000 new cases and 50,000 deaths each year), accounting for about 10% of cancer mortality (1). The incidence of colorectal cancer declined by 2.1% between 1992 and 1996, and current data suggest that mortality rates may also be declining. These trends may be attributable to increased screening efforts, early intervention with prophylactic polypectomy, and improved adjuvant therapies. This has encouraged further research in prevention, detection, and treatment of colorectal cancer.

During the recent past, investigators from a variety of disciplines have made important discoveries in the areas of carcinogenesis, screening and prevention, and anticancer therapy. Over time, these advances should contribute to continued reduction in the overall incidence and mortality of colorectal cancer. As an example, standard therapy for stages III and IV colorectal cancer, which remained stagnant for many years, has continuously evolved since 2000. The number of drugs and drug combinations available for treatment and prevention has continued to grow and now includes targeted agents.

This chapter reviews our current understanding of colorectal cancer, describes the known genetic mutations and risk factors, and outlines emerging screening, prevention, and therapeutic strategies, with particular emphasis on the approach taken at the University of Texas MD Anderson Cancer Center (MDACC).

Geographic Distribution

Colorectal cancer is more common in Western industrialized countries (ie, the United States, Canada, Scandinavia, northern and western Europe, and New Zealand) than in Asia, most of South America, and Africa (2). Since 1978, colon cancer mortality has declined in some western European countries and in the United States, while the incidence and mortality rates for colorectal cancer continues to rise in Japan and China (2). Individuals who migrate from known low-incidence regions assume the colon cancer risk of their adopted country, implicating interplay of environmental and genetic factors in the development of this disease. The age-specific incidence of colorectal cancer in the United States rises steadily, with more than 90% of cases diagnosed in patients 50 years of age or older. The male/female ratio for colon cancer is 1.34 while the ratio for rectal cancer is 1.73 (3).

Carcinogenesis: The Adenoma–Adenocarcinoma Sequence

Results from numerous studies, including those of Vogelstein group (4) and the National Polyp Study (5,6), suggest that colorectal neoplasia results from sequential accumulation of genetic and molecular alterations over many years, ultimately causing normal epithelium to transform into intraepithelial neoplasia (dysplasia) and then malignant epithelium. The morphologic adenoma–adenocarcinoma sequence that was recognized over 40 years ago is now known to begin with aberrant crypt foci and includes serrated lesions as well as traditional adenomas. Many distinct genetic ...

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