Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes

Sapna Syngal, MD, MPH, FACG,1,2,3 Randall E. Brand, MD, FACG,4 James M. Church, MD, FACG,5,6,7 Francis M. Giardiello, MD,8 Heather L. Hampel, MS, CGC9 and Randall W. Burt, MD, FACG10

1Brigham and Women’s Hospital, Boston, Massachusetts, USA; 2Dana Farber Cancer Institute, Boston, Massachusetts, USA; 3Harvard Medical School, Boston, Massachusetts, USA; 4Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA; 5Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio, USA; 6Sanford R Weiss, MD, Center for Hereditary Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, Ohio, USA; 7Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA; 8Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; 9Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA; 10Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Am J Gastroenterol 2015; 110:223–262; doi: 10.1038/ajg.2014.435; published online 3 February 2015
Received 12 September 2014; accepted 10 December 2014

Correspondence: Sapna Syngal, MD, MPH, FACG, Dana Farber Cancer Institute, 450 Brookline Avenue, Dana 1124, Boston, Massachusetts 02215, USA. E-mail:


This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer. Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives. When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives. Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient’s informed decision making. Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndromespecific cancers. This guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer.

Click the "Download PDF" button to read the full guideline.