Year: 2025
Type: article
Study design: Observational Study
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.
DOI: 10.1002/ueg2.70112
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, Collaborators GEOCODE and SECOC Consortia
Institutions: Royal Marsden NHS Foundation Trust, London North West Healthcare NHS Trust, Royal Marsden Hospital, St Mark's Hospital, Imperial College London, Chelsea and Westminster Hospital NHS Foundation Trust, University of Bonn, University Hospital Bonn, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Vall d'Hebron Hospital Universitari, Humanitas University, IRCCS Humanitas Research Hospital, Leiden University, Leiden University Medical Center, MD Anderson Cancer Center Madrid, Hospital General Universitario Gregorio Marañón, Hospital de Galdakao, Hospital Del Mar, Hospital Universitario Infanta Leonor, Hospital Clínico San Carlos, Hospital Universitario Ramón y Cajal, Hospital Universitario Fundación Alcorcón, Hospital Universitario General de Villalba, Instituto de Investigación Biomédica de Salamanca, Hospital Universitario Fundación Jiménez Díaz, Clinica Universidad de Navarra, Universidad de Salamanca, Instituto de Biología Molecular y Celular del Cáncer de Salamanca, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,930
Awards: OMICAS E INTELINGENCIA ARTIFICAL. HERRAMIENTAS PARA ENTENDER LOS MECANISMOS MOLECULARES DE LA RESISTENCA A INSULINA EN NIÑOS OBESOS DURANTE LA PUBERTAD., BUSQUEDA DE MARCADORES DE RIESGO DE CANCER COLORRECTAL EN ADULTO JOVEN: RESPUESTA INMUNE CONGÉNITA Y ADQUIRIDA. ESTUDIO CORRELATE, PAPEL DEL METABOLISMO DE CARBOHIDRATOS EN EL CANCER COLORRECTAL DE APARICION PRECOZ. POSIBLE IMPLICACION DE LA MICROBIOTA.
OpenAlex ID: W4414565242