Introduction

Colorectal cancer is the second leading cause of death from cancer at all sites in both sexes; an estimated 148,300 new cases of colorectal cancer and 56,600 deaths from the disease occurred in 2002 in the United States (American Cancer Society, 2003). Incidence rates vary significantly around the world. The highest age-adjusted rates (25 to 35 per 100,000) occur in North America, Western Europe, and Australia. Rates in Asia and Africa are low but are increasing with migration and westernization, largely because of dietary and environmental changes.

The colorectal cancer incidence in the United States and western countries is high among people older than 60 years of age but much lower in people under age 30 (0.86% to 3.2% of cases) and people under age 40 (2% to 6% of cases). The age distribution for colon cancer fits well with the multistage theory of tumorigenesis. This theory predicts an exponential time to onset for cancer, with the age-dependent slope depending on the number of events that are required for tumor development. For colon cancer, the model indicates that for most people, 4 to 6 events are needed for transformation of cells from normal colonic mucosa to carcinoma. Modeling of the different regions of the bowel indicates differences by site, with fewer events needed in models that include younger patients with cancer of the proximal colon (Dubrow et al, 1994).

One approach to identifying novel factors that predispose to colorectal cancer is the search for factors that decrease the age of onset of colorectal cancer. Genetic factors can have a profound effect in decreasing the age of onset of colorectal cancer. In addition, colorectal cancer trends show marked differences by country of origin. Our ongoing international studies have found a high incidence of very early onset colorectal cancer in Egypt not associated with familial or genetic factors (Soliman et al, 2001), suggesting that unique environmental factors predispose this population to colorectal cancer (Soliman et al, 1997). Early-onset cases throughout the world are more likely to show less favorable histologic subtypes, such as mucinous or signet ring cell, suggesting differences in etiology between early-onset cancers and cancers occurring at later ages. Individuals who have carcinomas with an unusual histologic subtype may receive better care in a tertiary care environment, where more of these cancers are treated.

A wide range of environmental and familial risk factors have been implicated as modifying the risk for colorectal cancer (Potter, 1999). In this chapter, we first provide a brief description of the epidemiologic methods used to characterize risk factors. We then summarize data concerning major epidemiologic and genetic risk factors for colorectal cancer. We also provide information about gene-gene and gene-environment interactions in the etiology of colorectal cancer.

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