Convergent mutational processes in esophageal and junctional adenocarcinomas across eight countries
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: ABSTRACT The incidence distribution of esophageal adenocarcinoma (EAC) and gastroesophageal junction (GEJ) cancers presents important geographic variations, yet the causes of these differences remain unclear. We analyzed 520 whole genomes from EAC/GEJ tumors across eight countries to examine the mutational forces shaping these cancers and their geographic variation. The mutational landscape was highly similar between EAC and GEJ tumors, and was dominated by signatures SBS17a/b, previously associated with reflux in EAC/GEJ. SBS17a/b were linked to obesity in EAC, supporting an indirect role in exacerbating reflux-mediated mutagenesis. Other established risk factors, such as tobacco smoking, did not yield a direct mutational footprint, pointing to non-mutagenic effects in EAC/GEJ. Nonetheless, geographic differences were present, with signatures related to endogenous cellular functions enriched in high-incidence populations. These findings provide new insights into the shared mutational forces that shape EAC and GEJ, as well as their geographic distribution.
Source: medRxiv
Authors: Laura Torrens, Sarah Moody, Jiali Pang, Behnoush Abedi-Ardekani, Haoran Zhang, Ammal Abbasi, Charles Nunn, Stephen Fitzgerald, Pilar Gallego-García, Valerie Gaborieau, Thomas Cattiaux, Priscilia Chopard, Saamin Cheema, Emily Thomas, Calli Latimer, Christine Carreira, Marcos Díaz-Gay, Maria Paula Curado, Charles Dzamalala, Felipe Fermandes Coimbra, Lorenzo Ferri, Rebecca C Fitzgerald, Alisa M Goldstein, Antonio Huertas-Salgado, Reza Malekzadeh, Diana Menya, Rui Manuel Reis, Felipe Ribeiro Pinto, Gholamreza Roshandel, Jonathan Yeung, Ana Carolina de Carvalho, Laura Humphreys, Ayesha Noorani, Ludmil B Alexandrov, Paul Brennan, Michael R Stratton, Sandra Perdomo
Institutions: Centre international de recherche sur le cancer, Wellcome Sanger Institute, University of California San Diego, Moores Cancer Center, Spanish National Cancer Research Centre, AC Camargo Hospital, University of Malawi, McGill University, University of Cambridge, National Institutes of Health, Division of Cancer Epidemiology and Genetics, Instituto Nacional de Cancerología, Digestive Disease Research Institute, Tehran University of Medical Sciences, Moi University, Hospital de Câncer de Barretos, University of Minho, Instituto Nacional de Câncer - INCA, Golestan University of Medical Sciences, University Health Network
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223388386