{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:17:49Z","timestamp":1783448269245,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) has raised considerable health concerns worldwide, with increasing incidence rates, specifically among younger populations. Despite remarkable progress in diagnosing and treating various diseases, the genetic basis of CRC remains only partially understood. This paper aims to examine novel genetic variants associated with CRC in Iranian patients. We performed whole\u2010exome sequencing (WES) in two Iranian families with a history of early\u2010onset CRC. Candidate variants were validated by Sanger sequencing and assessed for segregation. Pathogenicity was evaluated through comprehensive in silico analysis and the application of ACMG\/AMP guidelines. Analysis revealed two clinically significant variants. In Family 1, we identified a heterozygous stop\u2010gain variant in\n                    <jats:italic>MLH1<\/jats:italic>\n                    (c.1043T&gt;A, p.Leu348), a known pathogenic mutation consistent with Lynch syndrome. In Family 2, we discovered a previously undocumented heterozygous missense variant in\n                    <jats:italic>ERBB2<\/jats:italic>\n                    (c.2268G&gt;T, p.Arg756Ser). Through a detailed ACMG assessment, this\n                    <jats:italic>ERBB2<\/jats:italic>\n                    variant was classified as Likely Pathogenic based on its location in a critical tyrosine kinase domain, absence from population databases, and concordant deleterious in silico predictions. WES offers a deeper understanding of CRC genetics, suggesting potential biomarkers with promising applications for early diagnosis and targeted treatments, eventually improving patient\u2010related outcomes. The results of this study underscore the significant contribution of genetic screening to the well\u2010being of high\u2010risk families and offer valuable insights for targeted therapeutic approaches.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70166","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T09:24:16Z","timestamp":1767345856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exome Sequencing Identifies Variants in\n                    <i>MLH1<\/i>\n                    and\n                    <i>ERBB2<\/i>\n                    as Potential Cancer\u2010Predisposing Factors in Familial Early\u2010Onset Colorectal Cancer"],"prefix":"10.1002","volume":"42","author":[{"given":"Behnaz","family":"Bagheri","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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Mohsen\u2010Pour","sequence":"additional","affiliation":[{"name":"Zanjan Pharmaceutical Biotechnology Research Center Zanjan University of Medical Sciences  Zanjan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najmeh","family":"Salehi","sequence":"additional","affiliation":[{"name":"School of Biology, College of Science University of Tehran  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-2950","authenticated-orcid":false,"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 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