The aberrant crypt focus as a colorectal cancer precursor and biomarker of colorectal cancer risk

The aberrant crypt focus (ACF) has been investigated as a potential biomarker of colorectal cancer (CRC) risk. This thesis examines the features of ACF from the colorectums of individuals with CRC and individuals with benign diseases in an effort to validate the ACF as an appropriate biomarker in humans. ACF were found at a significantly higher frequency in persons with CRC compared to controls. Interestingly, dysplasia was uncommon in ACF from CRC and control patients. However, the frequency of ACF exhibiting hyperplastic compared to normal histology was found to be greater in the ACF from CRC patients. It was demonstrated that K-ras and APC mutations occur at this very early histological stage. Taken together, these results suggest that a subset of ACF have the molecular genetic features associated with the development of colorectal neoplasia. Moreover, it is concluded that ACF frequency, in combination with the histological and genetic features of ACF, may serve as a feasible in vitro biomarker of CRC risk.