Genetic testing for inherited colon cancer

The genes associated with each of the inherited syndromes of colon cancer have now been identified, and genetic testing is available for diagnosis. These syndromes include familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and, possibly, Cowden's syndrome. Clinical genetic testing approaches have been developed for each of these syndromes and are now a part of accepted clinical care. Disease-causing mutations can be found in the majority of families affected with one of the inherited syndromes, and, most importantly, once a mutation is found in an index case of the family, relatives can be tested for the presence or absence of that mutation with near 100% accuracy. Cancer screening and management in syndrome families is then based on the results of genetic testing. For the physician to order and properly interpret genetic tests, a basic understanding of the types of mutations that lead to inherited disease and the methods for detecting them is vital. These issues will be presented. Additional clinical issues somewhat unique to genetic testing include genetic counseling and informed consent for genetic testing, both of which will also be reviewed. Often the most difficult aspect of genetic testing is deciding which patients and families should undergo the testing. Furthermore, this issue is quite specific for each of the syndromes. Thus, following presentation of general principles of selection for genetic testing, a detailed approach for identifying persons who should undergo testing for each of the individual syndromes will be given, together with relevant descriptions of the syndromes. Finally, the ongoing work to discover new and possibly more common but less penetrant colon cancer susceptibility genes that cause common familial colon cancer will be presented.