Several groups have an increased risk of developing colorectal cancer: those with inflammatory bowel disease or colorectal polyps, individuals in families affected by the autosomal dominant conditions hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), and individuals who have a family history of colorectal neoplasia but are not part of families affected by HNPCC or FAP families.

The risk of cancer in patients with longstanding ulcerative colitis or Crohn’s disease is hard to quantify, but is thought to be similar for patients with the two conditions (28). A meta-analysis of 116 studies estimated that the cumulative probability of cancer in a patient with ulcerative colitis was 2% by 10 years, 8% by 20 years, and 18% by 30 years (29).

Studies have shown that adenomatous polyps left in situ progress from adenoma to cancer [reviewed in (30)]. These observations, coupled with indirect evidence, support the view that most colorectal carcinomas develop from adenomas. Although these lesions are usually removed when detected, the risk for recurrence three years after colonoscopic polypectomy is 30% to 40% (31,32). Investigation of factors related to occurrence and recurrence of polyps may provide information about the roles of exposures in the earlier stages of the adenoma–carcinoma sequence and, in turn, give clues as to likely routes for prevention of colorectal cancer. Adenoma recurrence is frequently used as a “model system” in intervention studies, the assumption being that an intervention that is effective in preventing recurrence in individuals with adenomas may also be effective in the prevention of colorectal cancer. Hyperplastic polyps also may exhibit malignant potential. These, and serrated adenomas, may be precursors of some right-sided colon cancers (33). Where pertinent, examples of studies of adenoma occurrence or recurrence are discussed later in this section.

Fewer than 10% of incident colorectal cancers are due to HNPCC and FAP (34). Excluding these syndromes, carcinomas and adenomas aggregate in families. Individuals who have a first-degree relative with colorectal cancer have around a twofold increased risk of developing the disease themselves (35–37). This pattern is probably not entirely explained by familial clustering of environmental factors (38). This points to the potential importance of genetic susceptibility factors, and the interaction of these with each other and with environmental factors, in causing the disease. Genetic susceptibility is discussed further later in this section.

Rebecca A. Barnetson and Malcolm G. Dunlop
Colon Cancer Genetics Group, University of Edinburgh, School of Molecular and Clinical Medicine and MRC Human Genetics Unit, Western General Hospital, Edinburgh, U.K.

References