Identification of patients at risk for hereditary colorectal cancer

Abstract

Diagnosis of hereditary colorectal cancer syndromes requires clinical suspicion and knowledge of such syndromes. Lynch syndrome is the most common cause of hereditary colorectal cancer. Other less common causes include familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome, and others. There have been a growing number of clinical and molecular tools used to screen and test at risk individuals. Screening tools include diagnostic clinical criteria, family history, genetic prediction models, and tumor testing. Patients who are high risk based on screening should be referred for genetic testing.

Keywords: Lynch syndrome; Peutz-Jeghers syndrome; familial adenomatous polyposis.

Figure 1

Family history gathering directed at identifying patients at high risk for a colorectal cancer predisposition syndrome. From: Gammon A, Kohlmann W, Burt R. Can we identify the high-risk patients to be screened? A genetic approach. Digestion 2007;76(1):7–19. Copyright: S. Karger AG, Basel, Switzerland.

Figure 2

Algorithm for genetic evaluation of individuals with colorectal cancer based on revised Bethesda guidelines and PREMM score. IHC, immunohistochemistry; MSI, microsatellite instability.*Other models may be used. Each model has its own prespecified cutoff (PREMM_1,2: http://www.dana-farber.org/pat/cancer/gastrointestinal/crc-calculator/default.asp; Barnetson: https://hnpccpredict.hgu.mrc.ac.uk/; MMR pro: http://astor.som.jhmi.edu/Bayes-Mendel/). ^†If loss of MLH1 expression, BRAF analysis should be performed. ^‡Surveillance recommendations based on personal and family history. From Grover S, Syngal S. Genetic testing in gastroenterology: Lynch syndrome. Best Pract Res Clin Gastroentrol 2009; 23:185–196. Reprinted with kind permission of Elsevier.