Klin Onkol 2019; 32(Suppl 2): 97-108. DOI: 10.14735/amko2019S97.
Background: It is estimated that 5–10% of colorectal cancers arise due to a known genetic syndrome. Individuals with these cancer syndromes are also at risk of extracolonic cancers. Polyposis and nonpolyposis hereditary syndromes are generally recognized. Inclusion of next-generation sequencing technology, especially multiple-gene panel testing, in routine laboratory practice has made identifying the causes of these diseases significantly easier. Purpose: To summarize current knowledge of the causes, clinical manifestations, diagnostic criteria, and recommendations for presymptomatic screening of individuals at risk of hereditary gastrointestinal polyposis and colorectal cancer syndromes. We dicuss currently defined syndromes detected by multiple-gene panel next-generation sequencing; these include constitutional mismatch repair deficiency (biallelic MLH1, MSH2, MSH6, PMS2 gene mutations), gastric adenocarcinoma and proximal polyposis of the stomach (APC gene), NTHL1-associated polyposis, polymerase proofreading-associated polyposis (POLD1, POLE genes), juvenile polyposis (SMAD4, BMPR1A genes), and serrated polyposis syndromes. Another aim is to summarize recent knowledge about well-known syndromes, including hereditary nonpolyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, MUTYH-associated polyposis, and Peutz–Jeghers and Cowden/PTEN hamartoma tumor syndromes. Conclusion: Awareness of hereditary polyposis/colon cancer syndromes enables early diagnosis and prevention of cancer in affected individuals and their relatives. Genetic counseling, presymptomatic testing of at-risk individuals, and efficient screening may be beneficial for affected families.
