ArticleInternational journal of cancer2026
KRAS-G12C: The neglected biomarker to detect patients with MUTYH-associated polyposis.
Article in International journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- KRAS-G12C: The neglected biomarker to detect patients with MUTYH-associated polyposis.International journal of cancer · 2026Article
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10 authors.
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Abstract
MUTYH-associated polyposis (MAP) is an underdiagnosed recessive syndrome that predisposes individuals to colorectal cancer (CRC) and exhibits phenotypic variability. Biallelic MUTYH inactivation leads to a somatic mutational signature with frequent KRAS-G12C mutations; however, despite being proposed as a marker for MAP, germline MUTYH testing in these patients remains limited. We assessed the utility of screening germline pathogenic variants (GPVs) in MUTYH among CRC cases with KRAS-G12C. A cohort of 220 KRAS-G12C CRC patients from two Brazilian oncology centers underwent targeted amplicon sequencing for the most prevalent MUTYH GPVs in Brazil. Comprehensive MUTYH sequencing was subsequently performed for monoallelic carriers. Overall, 25 (11.4%) patients carried at least one MUTYH 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 <60 years. Compared with non-carriers, MAP patients had an earlier CRC onset (49 vs. 59 years, p = 0.008), a higher prevalence of polyps (OR = 5.26; CI 95% 1.49-18.59; p = 0.036) and a family history of cancers (84.6% vs. 48.9%, p = 0.014), but fewer occurrences of metastasis (30.7% vs. 68.3%, p = 0.006) and stage IV tumors (30.8% vs. 68.3%, p = 0.029). Notably, most MAP cases (11/15) were not previously diagnosed, demonstrating that the strong association between KRAS-G12C mutations and the presence of MUTYH GPVs supports its use as a biomarker for referring patients to germline MUTYH testing, enabling appropriate follow-up, surveillance and preventive strategies for individuals at risk.
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