Commentary (Burt): Genetics of Colorectal Cancer

Colorectal cancer is undoubtedly one of the most genetically studied malignancies. In the past 20 years, substantial progress has been made in understanding the genetic and molecular pathogenesis of this cancer. It is instructive that the genes involved in the inherited colon cancer syndromes are the same genes involved in the etiology of most colorectal cancers. Familial adenomatous polyposis (FAP) and hereditatry nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) arise from mutations of the adenomatous polyposis coli (APC) gene and mismatch repair genes, respectively. Approximately 80% of sporadic colorectal cancers begin with APC mutations, while another 15% have a mismatch repair mutation occurring early in their pathogenesis. Additional mutations in different genes accumulate as polyps progress in both size and histopathology to colon cancer.