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Epidemiological data indicate that EOCRC incidence is increasing, despite the observed heterogeneity among countries. Although the cause for such increase remains obscure, \u224813% (range: 9\u201326%) of EOCRC patients carry pathogenic germline variants in known cancer predisposition genes, including 2.5% of patients with germline pathogenic variants in hereditary cancer genes traditionally not associated with CRC predisposition. Approximately 28% of EOCRC patients have family history of the disease. This article recapitulates current evidence on the inherited syndromes that predispose to EOCRC and its familial component. The evidence gathered support that all patients diagnosed with an EOCRC should be referred to a specialized genetic counseling service and offered somatic and germline pancancer multigene panel testing. The identification of a germline pathogenic variant in a known hereditary cancer gene has relevant implications for the clinical management of the patient and his\/her relatives, and it may guide surgical and therapeutic decisions. The relative high prevalence of hereditary cancer syndromes and familial component among EOCRC patients supports further research that helps understand the genetic background, either monogenic or polygenic, behind this increasingly common disease.<\/jats:p>","DOI":"10.3390\/cells10030710","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T14:08:16Z","timestamp":1616508496000},"page":"710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["The Inherited and Familial Component of Early-Onset Colorectal Cancer"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5636-8865","authenticated-orcid":false,"given":"Maria","family":"Daca Alvarez","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hospital Cl\u00ednic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-3033","authenticated-orcid":false,"given":"Isabel","family":"Quintana","sequence":"additional","affiliation":[{"name":"Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7813-1172","authenticated-orcid":false,"given":"Mariona","family":"Terradas","sequence":"additional","affiliation":[{"name":"Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-926X","authenticated-orcid":false,"given":"Pilar","family":"Mur","sequence":"additional","affiliation":[{"name":"Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0206-0539","authenticated-orcid":false,"given":"Francesc","family":"Balaguer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital Cl\u00ednic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0371-0844","authenticated-orcid":false,"given":"Laura","family":"Valle","sequence":"additional","affiliation":[{"name":"Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1053\/j.gastro.2019.07.055","article-title":"Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults","volume":"158","author":"Stoffel","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1136\/gutjnl-2019-319511","article-title":"Global patterns and trends in colorectal cancer incidence in young adults","volume":"68","author":"Siegel","year":"2019","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1053\/j.gastro.2010.01.054","article-title":"Hereditary and familial colon cancer","volume":"138","author":"Jasperson","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.giec.2020.03.001","article-title":"Colorectal Cancer in Persons Under Age 50: Seeking Causes and Solutions","volume":"30","author":"Patel","year":"2020","journal-title":"Gastrointest Endosc. 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