Biomarkers in colorectal cancer

Epidemiological studies have revealed that the major dietary constituents implicated in colorectal carcinogenesis are fat/red meat (causative) and calcium/fibre (protective). Biomarkers have been used in both animal studies and clinical trials to investigate the effect of dietary factors and chemotherapeutic agents on colon carcinogenesis. They can be used as short-term end-points when investigations based on the development of cancer are not feasible. Although they can help in elucidating dietary or pharmacological effects, important results should be confirmed with longer-term studies. Colon cancer develops through an adenoma-carcinoma sequence. The appearance of colonic polyps in individuals at risk for colon cancer has been used as an end-point in clinical trials to assess diets and pharmacological agents for their effect on colon carcinogenesis. Normal-appearing mucosa can contain small foci of aberrant crypts, which can be dysplastic and thought of as microadenomas. The appearance and growth of such foci have been used to assess the effect of dietary factors and chemopreventive agents in experimental animals. Increased proliferation both increases the sensitivity of the colon to carcinogenesis and may represent an early step in colon carcinogenesis. Etheno-DNA adducts are an end-product of lipid peroxidation processes, and are strongly pro-mutagenic lesions. High dietary levels of n-6 fatty acids appear to be important here and may also increase eicosanoid or isoprostane exposure and provide a selective growth stimulus for tumour precursor cells. Low dietary calcium may lead to inhibition of apoptosis and possibly to an increase in cell proliferation. In three recently completed intervention trials, calcium moderately reduced the recurrence of adenomas, but in one study fibre increased recurrence dramatically.