Hereditary colorectal cancer syndromes: Who to send for genetic testing

Genetic testing has become a mainstream approach for the diagnosis of a number of gastrointestinal cancer predisposition syndromes. These include familial adenomatous polyposis (FAP), Lynch syndrome, and the rare hamartomatous polyposis conditions of Peutz-Jegher syndrome, juvenile polyposis syndrome and Cowden syndrome. All of these have a marked increased risk for colon and other malignancies. FAP and the hamartomatous polyposis syndromes are most often recognized by clinical features including characteristic polyps of the gastrointestinal tract. Genetic testing verifies the diagnosis in an index case and allows precise genetic testing of family members to determine which of them needs syndrome specific screening and which needs only average risk screening. Lynch syndrome is more difficult as there is not a specific clinical phenotype. Nonetheless there is a high risk of colon cancer that often occurs at a young age. Colorecta and endometrial cancer tumor testing for microsatellite instability and for abnormal expression of the mismatch repair genes (the genes mutated in this disease) is a growing approach to find persons who should have genetic testing for Lynch syndrome. Additionally, risk based genetic testing is often indicated when tumor tissue is not available. Genetic testing is now sufficiently accurate that most persons and families with one of the inherited syndromes can be identified and appropriate cancer surveillance measures applied.