Inherited gastrointestinal cancer syndromes

Abstract

Inherited gastrointestinal (GI) cancer syndromes account for 5–10% of cancers of the GI tract. Surveillance is tailored to prevent cancer or enable its early detection. Lynch syndrome accounts for 3% of colorectal cancers (CRCs). It is caused by a germline pathogenic variant that affects one of four mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with a variant affecting MLH1 have the highest risk of developing CRC. Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a truncating mutation of the APC gene. It is characterized by the development of adenomas in the colon and upper GI tract. Almost 100% of patients who have not undergone a colectomy develop CRC, and 5% of FAP patients develop duodenal cancer. MUTYH-associated polyposis is an autosomal recessive cancer syndrome with a similar phenotype and surveillance strategy to FAP. Peutz–Jeghers syndrome is an autosomal dominant condition characterized by hamartomas of the GI tract; these patients are at increased risk of cancer of the GI tract, breast and pancreas. Juvenile polyposis syndrome is associated with the development of GI tract hamartomas and an associated increased risk of cancer of the colon and stomach.