Genetics of colorectal cancer

Introduction Colorectal cancer is a major public health problem in the developed world and is becoming increasingly prevalent in developing countries. The current annual world incidence is around 950 000 cases (Globocan, 2000). It is the most common cause of early cancer death in the non-smoking population. Recent developments have led to the isolation of a number of moderate- to high-risk cancer susceptibility genes for the disease. Identifying people with high-risk alleles offers real opportunities for application of preventive measures. Intensive surveillance to detect early cancer, or even prevent cancer by polyp removal, can be targeted by genotype information. Surgical intervention and chemoprevention guided by genetic information are also likely to be part of future armaments used to combat the disease. The last ten years has seen a number of exciting developments in understanding key molecular events involved in colorectal cancer susceptibility, which are beginning to provide new insight into the fundamental basis of the disease. In this chapter we will describe the major advances and how they are impacting diagnosis and clinical management of colorectal cancer. Colorectal cancer epidemiology The multifactorial etiology of colorectal cancer involves environmental factors as well as genetic susceptibility (see Chapter 14). There are large differences in global prevalence of the disease, which is generally four times higher in developed countries than in developing countries (IARC, WHO, 1997). Incidence rates also vary according to ethnicity (American Cancer Society, 2002), however the observed variation between countries is primarily due to the role of environmental factors.