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

United European gastroenterology journal

Authors: Penelope V Edwards, Kussai Giuma Ali Eloussta, Andrew Latchford, Omar Faiz, Huw Thomas, Filomena Liccardo, Nikhil Pawa, Robert Hüneburg, Jacob Nattermann, Andrew George, Francesc Balaguer, Marc Martí, Antonino Spinelli, Caterina Foppa, Noel F F C de Miranda, Irene López, Elena Hurtado, Fernando Jiménez, Marta Jiménez-Toscano, Edurne Álvaro, Gonzalo Sanz, Araceli Ballestero, José A Rueda, Cristina Viyuela, Lorena Brandáriz, Rosario Vidal-Tocino, Damián García-Olmo, Carlos Pastor, Rogelio González-Sarmiento, Andreana N Holowatyj, Terri McVeigh, José Perea, Kevin J Monahan

PURPOSE: The global incidence and mortality of early-age onset colorectal cancer (EOCRC, or CRC diagnosed under 50 years) has increased in recent decades. High-risk surveillance and personalised oncological treatment may improve patients' outcomes. This study aims to characterise real-world somatic and germline molecular profiles in European EOCRC patients.

PATIENTS AND METHODS: Consecutive patients across the UK, Spain, Germany and Italy from the GEOCODE and SECOC consortia were identified using electronic patient records. Clinicopathological, somatic and germline testing data were collected on EOCRC patients. Tests included mismatch repair (MMR), somatic next generation sequencing (NGS) and germline multi-gene panels.

RESULTS: Eight hundred ninety-three EOCRC patients were identified from 23 European centres (45.7% female, median age 42, range 14-49), predominantly in the distal colorectum: 205/893 (22.9%) patients with right-sided tumours, 302/893 (33.8%) left-sided tumours, 288/893 (32.2%) rectal tumours and 97/893 (10.8%) unknown. On somatic analysis, 735/893 (82.3%) of patients had pMMR tumours and 148/893 (16.5%) dMMR. Although 534/893 (59.7%) did not receive NGS somatic testing, somatic variants were detected in 233/359 (64.9%) of those tested. Germline variants were detected in 133/210 (63.3%) patients tested. Lynch syndrome was diagnosed in 93/210 (44.2%), of whom 17/93 (18.2%) presented with pMMR tumours. Systematic recording of family history in these real-world data was variable. In all patients with family history recorded, 153/484 (31.4%) patients reported a relative with CRC.

CONCLUSIONS: Our results support universal and paired somatic and germline multi-gene panels for all EOCRC patients, regardless of MMR status or family history. Systematic molecular testing approaches are necessary to address disparities in people with EOCRC. Larger unselected cohort studies would support validation of testing prediction models and estimates of clinically relevant variant actionability.

© 2025 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.

PMID: 41014296

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