Current Surgical Concepts in Lynch Syndrome and Familial Adenomatous Polyposis.

Abstract

Background: Approximately 5% of colorectal cancers (CRCs) are associated with hereditary cancer syndromes. The natural history of these syndromes differs from sporadic cancers, and due to their increased risk of metachronous carcinomas, surgical approaches also differ. This review focuses on the current recommendations for surgical treatment and what evidence has led to these recommendations in the most clinically relevant hereditary CRC syndromes: Lynch syndrome (LS) and (attenuated) familial adenomatous polyposis (FAP).

Summary: LS has no common phenotype and is caused by individual germline variants in one of the mismatch repair genes (MLH1, MSH2, MSH6, or PMS2). Because each gene is associated with a different risk of metachronous cancer, guidelines now differentiate between genes in their recommendations for oncology interventions. Classical and attenuated FAP are caused by germline mutations in the APC gene and have a characteristic phenotype. Although correlations exist between phenotype and genotype, the indication for surgery is predominantly based on clinical manifestation rather than specific gene mutations.

Key message: Currently, the recommendation on the two diseases tends to go in opposite directions: while some forms of FAP may require less extensive surgery, in some LS patients, more sophisticated knowledge of metachronous carcinoma risk leads to more extensive surgery.