{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T21:36:09Z","timestamp":1768080969891,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR\u2010112\u2010233"],"award-info":[{"award-number":["DMR\u2010112\u2010233"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The incidence of early\u2010onset colorectal cancer (CRC), which affects people under 50, is increasing for unknown reasons. Additionally, no underlying genetic cause is found in 20%\u201330% of patients suspected of having familial CRC syndrome. Whole exome sequencing (WES) has generated evidence for new genes associated with CRC susceptibility, but many patients remain undiagnosed. This study applied WES in five early\u2010onset CRC patients from three unrelated families to identify novel genetic variants that could be linked to rapid disease development. Furthermore, the candidate variants were validated using Sanger sequencing. Two heterozygote variations, c.1077\u20102A&gt;G and c.199G&gt;A, were found in the <jats:italic>MSH2<\/jats:italic> and the <jats:italic>MLH1<\/jats:italic> genes, respectively. Sanger sequencing analysis confirmed that these (likely) pathogenic mutations segregated in all the affected families' members. In addition, we identified a rare heterozygote variant (c.175C&gt;T) with suspected pathogenic potential in the <jats:italic>MAP3K1<\/jats:italic> gene; formally the variant is of uncertain significance (VUS). Our findings support the hypothesis that CRC onset may be oligogenic and molecularly heterogeneous. Larger and more robust studies are needed to understand the genetic basis of early\u2010onset CRC development, combined with novel functional analyses and omics approaches.<\/jats:p>","DOI":"10.1002\/kjm2.12715","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T13:25:45Z","timestamp":1686749145000},"page":"896-903","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Whole exome sequencing identifies <scp><i>MAP3K1<\/i><\/scp>, <scp><i>MSH2<\/i><\/scp>, and <scp><i>MLH1<\/i><\/scp> as potential cancer\u2010predisposing genes in familial early\u2010onset colorectal cancer"],"prefix":"10.1002","volume":"39","author":[{"given":"Nayeralsadat","family":"Fatemi","sequence":"first","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siang\u2010Jyun","family":"Tu","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine China Medical University Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin\u2010Chun","family":"Chung","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine China Medical University Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pardis Ketabi","family":"Moghadam","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehsan Nazemalhosseini","family":"Mojarad","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehdi","family":"Totonchi","sequence":"additional","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences  Tehran Iran"},{"name":"Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid 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