Genetics of Familial Colorectal Cancer Syndromes

There are three main familial colorectal syndromes: familial adenomatous polyposis (FAP), MYH-associated polyposis (MAP), and Lynch syndrome. FAP and MAP are characterized by numerous colonic adenomatous polyps. FAP is a dominantly inherited condition due to germline mutations in the APC gene, while MAP is a recessive condition caused by germline mutations in the MYH gene. Extra-colonic manifestations occur in both syndromes. Lynch syndrome (formerly known as hereditary non-polyposis colorectal cancer, or HNPCC) is a dominantly inherited syndrome characterized by early onset, usually proximally located, colorectal cancer, and a variety of extra-colonic tumors as well. It is caused by germline mutations in one of four mismatch repair genes: MLH1, MSH2, MSH6 and PMS2. The Lynch syndrome phenotype is typically not as obvious as that for FAP or MAP; fortunately, the molecular characteristics of Lynch-associated tumors can be used to identify affected individuals. Finally, it is now thought that the hamartomatous polyposis syndromes, namely Peutz-Jegher’s syndrome, juvenile polyposis, and Cowden’s syndrome, may also be associated with an increased risk of colorectal cancer.

Originally presented August 29, 2011 in Salt Lake City, Utah.

Lecture Presenter

Wade Samowitz, MD Wade Samowitz, MD
Professor, Department of Pathology, University of Utah School of Medicine
Pathologist, Anatomic Pathology, ARUP Laboratories

Dr. Samowitz is a staff pathologist for the Anatomic Pathology Division at ARUP, with a special interest in microsatellite instability testing. He is a professor of pathology at the University of Utah, specializing in gastrointestinal and hepatic pathology. He received his BA from Cornell University and his MD from SUNY Downstate. Dr. Samowitz completed residency training in anatomic pathology at the University of Chicago and fellowships in gastrointestinal pathology at Johns Hopkins Hospital. Dr. Samowitz is board certified in anatomic pathology. His research interests are in the genetics and molecular epidemiology of colorectal neoplasia.


After this presentation, participants will be able to:

  • Identify the phenotype and genetic basis for familial colorectal cancer syndromes.
  • Apply the molecular biology of mismatch repair deficiency in the work-up of Lynch syndrome.
  • Identify different strategies for Lynch syndrome screening.
  • Identify the phenotype and genetic basis for hamartomatous polyposes.

Sponsored by:

University of Utah School of Medicine, and ARUP Laboratories