The hypothesis of stem cell overpopulation was originally developed from a mathematical model of colon tumorigenesis [59], in which stem cell overpopulation was found to be the key event at the cellular level that links the initiating molecular event (an APC mutation) to the earliest tissue abnormality, a proliferative change in the mutant colonic crypts of FAP patients [60]. Here, APC is linked to Familial adenomatous polyposis.