Real‐world molecular testing in European early‐onset colorectal cancer
Author(s)
Type
Journal Article
Abstract
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.
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.
Date Issued
2025-12-01
Date Acceptance
2025-09-08
Citation
United European Gastroenterology Journal, 2025, 13 (10), pp.2012-2022
ISSN
2050-6406
Publisher
Wiley
Start Page
2012
End Page
2022
Journal / Book Title
United European Gastroenterology Journal
Volume
13
Issue
10
Copyright Statement
© 2025 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Publication Status
Published
Date Publish Online
2025-09-27