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Biallelic\n                    <jats:italic>MUTYH<\/jats:italic>\n                    inactivation leads to a somatic mutational signature with frequent\n                    <jats:italic>KRAS<\/jats:italic>\n                    \u2010G12C mutations; however, despite being proposed as a marker for MAP, germline\n                    <jats:italic>MUTYH<\/jats:italic>\n                    testing in these patients remains limited. We assessed the utility of screening germline pathogenic variants (GPVs) in\n                    <jats:italic>MUTYH<\/jats:italic>\n                    among CRC cases with\n                    <jats:italic>KRAS<\/jats:italic>\n                    \u2010G12C. A cohort of 220\n                    <jats:italic>KRAS<\/jats:italic>\n                    \u2010G12C CRC patients from two Brazilian oncology centers underwent targeted amplicon sequencing for the most prevalent\n                    <jats:italic>MUTYH<\/jats:italic>\n                    GPVs in Brazil. Comprehensive\n                    <jats:italic>MUTYH<\/jats:italic>\n                    sequencing was subsequently performed for monoallelic carriers. Overall, 25 (11.4%) patients carried at least one\n                    <jats:italic>MUTYH<\/jats:italic>\n                    GPV; among these, 15 (6.8%) were biallelic and classified as MAP and 10 (4.5%) were monoallelic. The MAP detection rate was 10.9% in patients &lt;60\u2009years. Compared with non\u2010carriers, MAP patients had an earlier CRC onset (49 vs. 59\u2009years,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008), a higher prevalence of polyps (OR\u2009=\u20095.26; CI 95% 1.49\u201318.59;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.036) and a family history of cancers (84.6% vs. 48.9%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.014), but fewer occurrences of metastasis (30.7% vs. 68.3%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006) and stage IV tumors (30.8% vs. 68.3%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.029). Notably, most MAP cases (11\/15) were not previously diagnosed, demonstrating that the strong association between\n                    <jats:italic>KRAS<\/jats:italic>\n                    \u2010G12C mutations and the presence of\n                    <jats:italic>MUTYH<\/jats:italic>\n                    GPVs supports its use as a biomarker for referring patients to germline\n                    <jats:italic>MUTYH<\/jats:italic>\n                    testing, enabling appropriate follow\u2010up, surveillance and preventive strategies for individuals at risk.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70281","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:39:32Z","timestamp":1764941972000},"page":"1588-1598","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>KRAS<\/i>\n                    <\/scp>\n                    \u2010\n                    <scp>G12C<\/scp>\n                    : The neglected biomarker to detect patients with\n                    <scp>\n                      <i>MUTYH<\/i>\n                    <\/scp>\n                    \u2010associated polyposis"],"prefix":"10.1002","volume":"158","author":[{"given":"Ana Beatriz Deleame","family":"Medeiros","sequence":"first","affiliation":[{"name":"Clinical and Functional Genomics, A. C. Camargo Cancer Center  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Oliveira","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology A. C. Camargo Cancer Center  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Claudio","family":"Casali\u2010da\u2010Rocha","sequence":"additional","affiliation":[{"name":"Oncogenetics Department A. C. Camargo Cancer Center  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Aguiar","family":"Junior","sequence":"additional","affiliation":[{"name":"Colorectal Tumors Reference Center, A. C. Camargo Cancer Center  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virgilio","family":"Souza e Silva","sequence":"additional","affiliation":[{"name":"Colorectal Tumors Reference Center, A. C. 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