Each year colorectal cancer affects 32 000 people in the UK and is responsible for around 22 000 deaths. In males it is second only to lung cancer and in females it falls third behind lung and breast cancer. In the developed world, life-time risk of colorectal cancer is around 1: 25 and this is increased by genetic predisposition and certain conditions such as chronic colitis. Colorectal cancer is mainly a disease of the elderly with a marked rise in incidence after age 70 years, however, 10% of individuals are under age 55 years at diagnosis.
In 1972, Burkitt described the relationship between diet and incidence of bowel cancer; he hypothesised that a diet rich in fibre was associated with regular bulky stools and reduced bowel carcinogenesis, perhaps by reducing exposure of colonic mucosa to dietary carcinogens. It does seem likely that the combination of high fibre and low fat may be protective against bowel cancer. Protection against colorectal carcino-genesis is also derived from dietary supplements of calcium and folate and evidence from the Nurses Health Study (North America) suggested that oestrogen in the form of hormone replacement therapy (HRT) lowers the incidence of colorectal neoplasia. There has been interest in the potential influence of non-steroidal anti-inflammatory drugs in colorectal carcinogenesis. Cyclooxygenase (COX)-2 inhibition appears to have potent effects on the colonic mucosa, increasing apoptosis and reducing cellular proliferation. It is also likely that these drugs function through COX-independent mechanisms. Impressive effects on the growth on adenomas have been described in certain polyposis syndromes and uncontrolled population studies suggest a reduction in colorectal cancer associated mortality. However, these effects may be subject to many confounding factors and the exact influence on colorec-tal cancer incidence has yet to be determined.
Chronic inflammatory conditions often predispose to car-cinogenesis and in the colon and rectum this is best demonstrated by chronic UC. The risk of developing malignancy is related to the duration and extent of colitis. An approximate incidence of 10% per annum after a decade of extensive colitis is often cited. However, careful surveillance for dysplasia and precursor lesions followed by colectomy can reduce this risk. Similar risks and surveillance strategies apply to Crohn's colitis.
Vogelstein has proposed a model for colorectal carcinogenesis; with cancer resulting from an accumulation of somatic genetic defects manifested in the progression from small adenoma to larger adenoma and ultimately cancer. The time course to this endpoint is around 10 years but typically, conditions which lead to familial predisposition hasten this pathway to carcinogenesis with inherited mutations in the critical cancer genes or systems which maintain the integrity of DNA replication and repair. Examples of this are seen in familial adenomatous polyposis where an inheritable inactivating mutation in the antigen presenting cells (APC) gene occurs and hereditary non-polyposis colorectal cancer (HNPCC) where defects in DNA mismatch repair genes result in a high frequency of mutation.
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