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Real-World Molecular Testing in European Early-Onset Colorectal Cancer.

Penelope V Edwards1,2,3, Kussai Giuma Ali Eloussta3, Andrew Latchford1

  • 1The Centre for Familial Intestinal Cancer, St Mark's Hospital, London Northwest Healthcare Trust, London, UK.

United European Gastroenterology Journal
|September 27, 2025
PubMed
Summary
This summary is machine-generated.

Early-age onset colorectal cancer (EOCRC) molecular profiles reveal high rates of Lynch syndrome and actionable variants. Universal somatic and germline testing is recommended for all EOCRC patients to improve outcomes.

Keywords:
colorectal cancerearly onsetgermlinelynch syndromemismatch repairreal‐world datasomatic

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Global incidence and mortality of early-age onset colorectal cancer (EOCRC) are rising.
  • Personalized oncological treatment and high-risk surveillance are crucial for improving EOCRC patient outcomes.

Purpose of the Study:

  • To characterize the real-world somatic and germline molecular profiles of European EOCRC patients.
  • To identify potential targets for personalized treatment strategies in EOCRC.

Main Methods:

  • Retrospective analysis of consecutive EOCRC patients from UK, Spain, Germany, and Italy.
  • Collection of clinicopathological, somatic, and germline testing data, including mismatch repair (MMR) status, next-generation sequencing (NGS), and multi-gene panels.
  • Data from GEOCODE and SECOC consortia were utilized.

Main Results:

  • 893 EOCRC patients were analyzed (median age 42).
  • Somatic analysis revealed 16.5% dMMR tumors. Among tested patients, 64.9% had detectable somatic variants.
  • Germline testing identified variants in 63.3% of patients, with Lynch syndrome diagnosed in 44.2% of those tested.
  • Family history recording was variable, with 31.4% reporting a family history of CRC.

Conclusions:

  • Universal paired somatic and germline multi-gene panel testing is supported for all EOCRC patients.
  • Systematic molecular testing is essential to address disparities in EOCRC care.
  • Further research with larger cohorts is needed to validate predictive models and assess variant actionability.