Rechercher
image du produit
Lancet Oncology, The

S'abonner

Patterns in genomic mutations among patients with early-onset colorectal cancer: an international, multicohort, observational study - 29/07/25

Doi : 10.1016/S1470-2045(25)00239-6 
Jinming Li, MD a, b, *, Yedong Pan, MD a, b, *, Fanying Guo, MD a, b, *, Changzheng Wang, MD a, b, *, Lei Liang, MD a, b, *, Peilong Li, MD c, *, Wenjie Liang, ProfMD d, *, Peng Lian, ProfMD a, b, *, Yikuan Chen, MD a, b, Yongzhi Yang, MD a, b, Wanrun Lin, MD e, Xinxiang Li, ProfMD a, b, †, José Perea, MD PhD f, g, †, Wouter R L Hendrickx, MD h, i, †, Andreana N Holowatyj, PhD MSCI j, k, l, m, †, Xingyi Guo, PhD j, k, †, Lutao Du, ProfMD PhD n, †, Frank A Sinicrope, MD o, †, Yanlei Ma, ProfMD PhD a, b, †, ⁎
a Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China 
b Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 
c Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong, China 
d Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China 
e Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 
f Institute of Biomedical Research of Salamanca, Salamanca, Spain 
g Surgery Department, Vithas Arturo Soria University Hospital, Madrid, Spain 
h Tumor Biology and Immunology Lab, Research Branch, Sidra Medicine, Al-Rayyan, Qatar 
i College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar 
j Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA 
k Vanderbilt–Ingram Cancer Center, Nashville, TN, USA 
l Vanderbilt University School of Medicine, Nashville, TN, USA 
m Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA 
n Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Provincial Key Laboratory of Innovation Technology in Laboratory Medicine, Shandong, China 
o and Division of Medical Oncology, Mayo Clinic Alix School of Medicine, Mayo Comprehensive Cancer Center, Rochester, MN, USA 

*Correspondence to: Prof Yanlei Ma, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghai200032China

Summary

Background

The increasing incidence of early-onset colorectal cancer (age <50 years; EOCRC) shows a dramatic growing trend globally, while late-onset colorectal cancer (LOCRC) is gradually decreasing. We aimed to characterise the distinct mutational landscape of EOCRC in an effort to inform age-specific clinical management.

Methods

In this observational study, we analysed whole-exome sequencing and clinical-grade targeted sequencing data from seven cohorts (the Memorial Sloan Kettering Cancer Center [MSKCC] cohort [the USA], the Leiden University Medical Center cohort [the Netherlands], the Nigerian African Research Group for Oncology [ARGO] cohort [Nigeria], the Genomics Evidence Neoplasia Information Exchange [GENIE] Project [Canada, France, Spain, and the USA], the Sun Yat-sen University Cancer Center (SYSUCC) cohort [China], the Asan Medical Center cohort [South Korea], and the Fudan University Shanghai Cancer Center–Colorectal Cancer [FUSCC-CRC] cohort [China]) across Canada, China, France, Nigeria, South Korea, Spain, the Netherlands, and the USA. Eligible patients were aged 18 years or older with a confirmed diagnosis of colorectal adenocarcinoma or mucinous adenocarcinoma. Samples were categorised into hypermutated (tumour mutational burden [TMB] >15 mutations per megabase) and non-hypermutated (TMB ≤15 mutations per megabase) groups. We evaluated the TMB difference between EOCRC and LOCRC using gamma regression and compared genomic mutation data between EOCRC and LOCRC using multiple logistic regression and pathway enrichment analysis. The primary study objective was to compare genomic mutational patterns between EOCRC and LOCRC, stratified by TMB groups.

Findings

Between Jan 1 and Dec 31, 2024, 17 133 tumour samples from patients with colorectal cancer in eight countries were analysed (Canada [n=218], China [n=3009], France [n=62], Nigeria [n=64], South Korea [n=44], Spain [n=250], the Netherlands [n=281], and the USA [n=13 205]). Among 17 133 patients, 9452 (55·2%) were male, 7681 (44·8%) were female, 10 174 (59·4%) were White, 3904 (22·8%) were Asian or Pacific Islander, 983 (5·7%) were Black, and 4983 (29·1%) had EOCRC. In hypermutated colorectal cancer, EOCRC exhibited a significantly higher TMB compared with LOCRC (mean ratio 1·11 [95% CI 1·06–1·16]; p<0·0001). In non-hypermutated colorectal cancer, EOCRC showed a significantly lower TMB than LOCRC after adjusting for skewness (mean ratio 2·92 [95% CI 2·88–2·96]; p<0·0001). In hypermutated colorectal cancer, a total of 23 genes, including APC (EOCRC 464 [75·0%] of 619 vs LOCRC 891 [58·6%] of 1521; odds ratio [OR] 2·00 [95% CI 1·59–2·51]; adjusted p<0·0001), KRAS (EOCRC 331 [53·3%] of 621 vs LOCRC 488 [32·0%] of 1526; OR 2·35 [95% CI 1·91–2·89]; adjusted p<0·0001), and CTNNB1 (EOCRC 196 [31·6%] of 621 vs LOCRC 274 [18·0%] of 1526; OR 2·15 [95% CI 1·70–2·72]; adjusted p<0·0001), and TCF7L2 (EOCRC 294 [51·2%] of 574 vs LOCRC 489 [35·0%] of 1398; OR 2·01 [95% CI 1·62–2·50]; adjusted p<0·0001), displayed elevated mutation frequencies in EOCRC compared with LOCRC, whereas only BRAF (EOCRC 97 [15·6%] of 621 vs LOCRC 674 [44·2%] of 1526; OR 0·27 [95% CI 0·21–0·35]; adjusted p<0·0001) and RNF43 (EOCRC 225 [39·3%] of 573 vs LOCRC 778 [53·9%] of 1444; OR 0·61 [95% CI 0·49–0·76]; adjusted p=0·0015) were less frequently mutated in EOCRC than in LOCRC. In non-hypermutated colorectal cancer, only TP53 (EOCRC 3468 [79·5%] of 4362 vs LOCRC 7825 [73·7%] of 10 624; OR 1·37 [95% CI 1·25–1·50]; adjusted p<0·0001) showed a higher mutation frequency in EOCRC, while nine genes had lower mutation frequencies, including BRAF (EOCRC 274 [6·3%] of 4362 vs LOCRC 909 [8·6%] of 10 624; OR 0·70 [95% CI 0·60–0·81]; adjusted p=0·00024) and KRAS (EOCRC 1794 [41·1%] of 4362 vs LOCRC 4840 [45·6%] of 10624; OR 0·83 [95% CI 0·77–0·89]; adjusted p=0·00019).

Interpretation

Within hypermutated colorectal cancer, younger patients exhibited a higher mutational burden than older patients. Our study reveals an abnormal accumulation of distinct somatic mutations in hypermutated EOCRC, the pattern of which might be contributing to the alarming rise in the incidence of EOCRC over the past decades. Our results support the need for EOCRC-specific molecular profiling to guide clinical practice.

Funding

National Natural Science Foundation of China and the Shanghai Science and Technology Development Fund.

Le texte complet de cet article est disponible en PDF.

Plan


© 2025  Elsevier Ltd. Tous droits réservés.
Ajouter à ma bibliothèque Retirer de ma bibliothèque Imprimer
Export

    Export citations

  • Fichier

    •

  • Contenu

    •

Vol 26 - N° 8

P. 1055-1066 - août 2025 Retour au numéro
Article précédent Article précédent
  • Total neoadjuvant treatment with short-course radiotherapy followed by sintilimab plus capecitabine–oxaliplatin versus short-course radiotherapy followed by capecitabine–oxaliplatin in patients with locally advanced rectal cancer (SPRING-01): a single-centre, open-label, phase 2, randomised controlled trial
  • Feng Tian, Honghai Dai, Dan Sha, Yuanzi Yu, Haiyan Jing, Cong Sun, Liang Shang, Yubo Liu, Renxiang Feng, Jun Li, Hongjun Liu, Yuezhi Chen, Yulong Shi, Jinshen Wang, Hongqing Zhuo, Xiaoqiao Zhang, Guodong Lian, Wei Chong, Hao Chen, Zhe Yang, Leping Li, Changqing Jing
| Article suivant Article suivant
  • Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial
  • Vania Hungria, Paweł Robak, Marek Hus, Vera Zherebtsova, Christopher Ward, P Joy Ho, Roman Hájek, Kihyun Kim, Sebastian Grosicki, Hanlon Sia, Adam Bryant, Marcelo Pitombeira de Lacerda, Gracia Aparecida Martinez, Anna Sureda Balarí, Irwindeep Sandhu, Claudio Cerchione, Peter Ganly, Meletios A Dimopoulos, Chengcheng Fu, Mamta Garg, Al-Ola Abdallah, Moshe E Gatt, Albert Oriol Rocafiguera, Michele Cavo, Robert Rifkin, Tomoaki Fujisaki, Michał Mielnik, Joseph Ficek, Alejandro Mantero, Nick Pirooz, Sybil Varghese, Joe Lee, Astrid McKeown, Rachel Rogers, Hena Baig, Lydia Eccersley, Sumita Roy-Ghanta, Pralay Mukhopadhyay, Jacqueline Nielsen, Joanna Opalinska, María-Victoria Mateos, DREAMM-7 study investigators

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

Elsevier s'engage à rendre ses eBooks accessibles et à se conformer aux lois applicables. Compte tenu de notre vaste bibliothèque de titres, il existe des cas où rendre un livre électronique entièrement accessible présente des défis uniques et l'inclusion de fonctionnalités complètes pourrait transformer sa nature au point de ne plus servir son objectif principal ou d'entraîner un fardeau disproportionné pour l'éditeur. Par conséquent, l'accessibilité de cet eBook peut être limitée. Voir plus

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL

EM-CONSULTE.COM est déclaré à la CNIL, déclaration n° 1286925.

En application de la loi nº78-17 du 6 janvier 1978 relative à l'informatique, aux fichiers et aux libertés, vous disposez des droits d'opposition (art.26 de la loi), d'accès (art.34 à 38 de la loi), et de rectification (art.36 de la loi) des données vous concernant. Ainsi, vous pouvez exiger que soient rectifiées, complétées, clarifiées, mises à jour ou effacées les informations vous concernant qui sont inexactes, incomplètes, équivoques, périmées ou dont la collecte ou l'utilisation ou la conservation est interdite.
Les informations personnelles concernant les visiteurs de notre site, y compris leur identité, sont confidentielles.
Le responsable du site s'engage sur l'honneur à respecter les conditions légales de confidentialité applicables en France et à ne pas divulguer ces informations à des tiers.

Tout le contenu de ce site: Copyright © 2026 Elsevier, ses concédants de licence et ses contributeurs. Tout les droits sont réservés, y compris ceux relatifs à l'exploration de textes et de données, a la formation en IA et aux technologies similaires. Pour tout contenu en libre accès, les conditions de licence Creative Commons s'appliquent.