Genetic hits and mutation rate in colorectal tumorigenesis: versatility of Knudson's theory and implications for cancer prevention.

The multistep model of carcinogenesis is now widely accepted for colorectal cancer and other common epithelial tumors of the adult. The challenges ahead are to define the number of genetic hits necessary for conversion of a normal cell into a cancer cell and to determine whether the observed increase in the mutation rate (mutator phenotype) is required. The beauty of Knudson's two-hit theory is its ability to explain diverse experimental situations and guide specific predictions, including some directly relevant to cancer prevention.