{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:16:42Z","timestamp":1787062602046,"version":"build-2736575974"},"reference-count":81,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) incidence in young adults is rising. Identifying genetic risk factors is fundamental for the clinical management of patients and their families. This study aimed to identify clinically significant germline variants among young adults with CRC. Whole\u2010exome sequencing data of blood\u2010derived DNA from 133 unrelated young CRC patients (&lt;55\u2009years of age) underwent a comprehensive analysis of 133 cancer\u2010predisposition\/implicated genes. All patient tumors were evaluated for mismatch repair deficiency (dMMR). Among 133 patients (aged 16\u201354\u2009years), 15% (20\/133) had clinically actionable pathogenic or likely pathogenic (P\/LP) variants in at least 1 well established cancer\u2010predisposing gene: dMMR genes (6),\n                    <jats:italic>MUTYH<\/jats:italic>\n                    [bi\u2010allelic (2), mono\u2010allelic (3)],\n                    <jats:italic>RNF43<\/jats:italic>\n                    (1),\n                    <jats:italic>BMPR1A<\/jats:italic>\n                    (1),\n                    <jats:italic>BRCA2<\/jats:italic>\n                    (4),\n                    <jats:italic>ATM<\/jats:italic>\n                    (1),\n                    <jats:italic>RAD51C<\/jats:italic>\n                    (1), and\n                    <jats:italic>BRIP1<\/jats:italic>\n                    (1). Five patients (4%) had variants in genes implicated in cancer but where the significance of germline variants in CRC risk is uncertain:\n                    <jats:italic>GATA2<\/jats:italic>\n                    (1),\n                    <jats:italic>ERCC2<\/jats:italic>\n                    (mono\u2010allelic) (1),\n                    <jats:italic>ERCC4<\/jats:italic>\n                    (mono\u2010allelic) (1),\n                    <jats:italic>CFTR<\/jats:italic>\n                    (2). Fourteen (11%) had dMMR tumors. Eighteen (14%) reported a first\u2010degree relative with CRC, but only three of these carried P\/LP variants. Three patients with variants in polyposis\u2010associated genes showed no polyposis (one each in\n                    <jats:italic>MUTYH<\/jats:italic>\n                    [bi\u2010allelic],\n                    <jats:italic>RNF43<\/jats:italic>\n                    , and\n                    <jats:italic>BMPR1A<\/jats:italic>\n                    ). Approximately one in five young adults in our series carried at least one P\/LP variant in a cancer\u2010predisposing\/implicated gene; 80% of these variants are currently considered clinically actionable in a familial cancer setting. Family history and phenotype have limitations for genetic risk prediction; therefore multigene panel testing and genetic counseling are warranted for all young adults with CRC regardless of those two factors.\n                  <\/jats:p>","DOI":"10.1002\/gcc.23011","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T03:04:40Z","timestamp":1636599880000},"page":"105-113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Survey of germline variants in cancer\u2010associated genes in young adults with colorectal cancer"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-0619","authenticated-orcid":false,"given":"Reger R.","family":"Mikaeel","sequence":"first","affiliation":[{"name":"Department of Haematology and Oncology The Queen Elizabeth Hospital  Woodville South South Australia Australia"},{"name":"SAHMRI Colorectal Node Basil Hetzel 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