Defining the clinical phenotype of hereditary nonpolyposis colorectal cancer

Clinically, HNPCC has been defined according to the Amsterdam criteria. HNPCC can now be diagnosed at the molecular level by detecting germline mutations in genes involved in mismatch repair. A current problem is to determine the prevalence of HNPCC mutations in colon cancer patients with limited or no family history. Our data suggest that most HNPCC mutations occur in families and have high or moderate penetrance. New or low penetrance HNPCC mutations probably do not contribute significantly to the risk of colorectal cancer in the general population. Furthermore, germline HNPCC mutations are not responsible for the phenotype of patients with multiple or early-onset colonic adenomas.