Intermediate effect markers for colorectal cancer

Abstract

Recurrence or regression of adenomatous polyps is considered to be both a biomarker of risk and an intermediate (surrogate) end-point. The observational epidemiology of adenomas resembles closely that of invasive cancer, and the findings in chemoprevention trials that have been completed closely mirror that common epidemiology. Although it is possible that both the clinical trials and the epidemiology may be wrong, these common findings suggest that adenomas in general are valid end-points. Aberrant crypt foci show promise as biomarkers, both as markers of risk and as intermediate end-points for chemoprevention trials. If issues of cost can be overcome, assessment of ras mutations in stool appears to be a promising technique for screening for large bowel neoplasms. The lack of specificity of the technique limits its utility as a sole end-point in prevention studies, however. Mucosal proliferation has been used both as a biomarker of risk and as an intermediate end-point. The utility of these measures is not clear, however, since there has been discordance between the epidemiological findings regarding proliferation and established risk factors for colorectal neoplasia. The inherent variability of the measures and the technical problems associated with their use are further impediments. However, rectal mucosal proliferation may be suitable for studies in single institutions, or in consortia with very aggressive quality control.