A major role for Wnt pathway activation in the genesis of these cancers is highlighted by the fact that nearly 100% of all non-hereditary colorectal cancers exhibit inappropriate activation of the Wnt pathway, primarily due to mutations in the destruction complex (e.g., loss-of-function of APC/Axin or gain-of-function of β-catenin). This evidence concerns the gene APC and familial colorectal cancer.