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Knowledge of genetic susceptibility to gastrointestinal cancers is constantly evolving with identification of new genes. Similarly, a better understanding of the genotype/phenotype relationship in patients with Lynch syndrome (LS) or familial adenomatous polyposis (FAP) is leading to more individualised surveillance recommendations. In addition, molecular profiling of patients with cancer has been shown to guide targeted therapies, such as immunotherapy. Specialists involved in the care of patients with gastrointestinal cancer should be familiar with the main hereditary cancer syndromes and refer patients to specialised cancer genetic units for adequate genetic counselling and to address specific concerns associated to each genetic susceptibility. These guidelines aim to summarise the evidence-based data on hereditary colorectal cancer (CRC), gastric cancer (GC) and pancreatic cancer (PC) and provide useful clinical recommendations for identification and management of patients with hereditary gastrointestinal cancers. LS accounts for 1%–3% of all CRC diagnoses [1.Lynch H.T. de la Chapelle A. Hereditary colorectal cancer.N Engl J Med. 2003; 348: 919-932Crossref PubMed Scopus (1536) Google Scholar]. It is caused by germline mutations in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6 or PMS2) or epithelial cell adhesion molecule (EPCAM, which causes epigenetic silencing of MSH2) and has an autosomal dominant inheritance. More than 70% of mutations are identified in MLH1, MSH2 or EPCAM in tumours with microsatellite instability (MSI)-high. LS is characterised by an increased lifetime risk of CRC (30%–73%) and extracolonic malignancies such as endometrial (30%–51%), ovarian (4%–15%), gastric (up to 18%), small bowel (3%–5%), urinary tract (2%–20%), pancreatic (4%), brain or cutaneous gland tumours [2.Engel C. Loeffler M. Steinke V. et al.Risks of less common cancers in proven mutation carriers with Lynch syndrome.J Clin Oncol. 2012; 30: 4409-4415Crossref PubMed Scopus (187) Google Scholar, 3.Win A.K. Young J.P. Lindor N.M. et al.Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study.J Clin Oncol. 2012; 30: 958-964Crossref PubMed Scopus (227) Google Scholar, 4.Samadder N.J. Smith K.R. Wong J. et al.Cancer risk in families fulfilling the Amsterdam criteria for Lynch syndrome.JAMA Oncol. 2017; 3: 1697-1701Crossref PubMed Scopus (12) Google Scholar]. The carriers of pathogenic variants in MLH1 and MSH2 genes have a substantially higher risk of CRC cancer with younger age at diagnosis compared with carriers of MSH6 or PMS2 pathogenic variants. The cumulative incidence of endometrial and urinary tract cancers is higher in MSH2 carriers [5.Moller P. Seppala T. Bernstein I. et al.Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database.Gut. 2017; 66: 464-472Crossref PubMed Scopus (223) Google Scholar]. Data on cancer risk estimates for carriers of an EPCAM deletion is still limited. Historically, two LS clinical phenotypes have been described in those individuals with germline gene pathogenic variants with the of tumours or of cutaneous gland tumours et molecular of Engl J Med. PubMed Scopus Google Scholar, in J PubMed Scopus Google Scholar]. a or has been described in those individuals are or for pathogenic variants in the gene and is characterised by and tumours et criteria for mismatch repair of the for PubMed Scopus Google Scholar, M. et and of mismatch repair J PubMed Scopus Google Scholar]. in the genes to of DNA in as in the to the in the the LS tumours the of the by on CRC tumours has a and of and and is to et of for Lynch syndrome patients with colorectal Clin Oncol. PubMed Scopus Google Scholar]. of of of MLH1 and to of the MLH1 associated with mutation in of MLH1 or with of PMS2 is of the MLH1 in the for mutation should be first Similarly, of MLH1 or with of PMS2 is in of the MLH1 should be first mutations in CRC and endometrial cancer have been by with mutations in genes have a molecular LS as with and the of M. et of as a for Lynch syndrome and molecular for patients with colorectal Oncol. 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