Background: A better understanding of the molecular basis of hereditary colorectal cancer syndromes such as hereditary nonpolyposis colorectal cancer syndrome (HNPCC) and familial adenomatous polyposis (FAP) has profound consequences for both the diagnosis and (prophylactic) treatment of (pre)malignant neoplastic lesions.
Discussion: Sequence analysis of the underlying genes for these conditions and the detection of disease-causing genetic alterations in an index patient enable predictive testing for individuals at risk within an affected family. However, the clinical implications of predictive molecular testing depend on the overall penetrance and variability in the expression of pathogenic mutations. The extent of these parameters differs considerably among the various known hereditary colorectal cancer syndromes. Hence the integration of genetic information into the daily surgical practice remains challenging.
Conclusions: This review provides an update on the indications for family assessment, purpose and limitations of the genetic testing and resulting recommendations for prophylactic surgery in FAP and HNPCC.