Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Approximately half of all pancreatic cancers cannot be explained by known risk factors. Here we present the results of mutational signature analysis in 495 cases of pancreatic cancer from nine countries to explore whether there are previously unknown mutagenic exposures acting on pancreatic cancer genomes. The mutational signature landscape was consistent between countries. We identified one signature not previously found in pancreatic cancer, SBS111, which does not have a confirmed aetiology but is present in >99% of cases and contributes on average 26% of the total mutation burden. No evidence was found for mutational signatures known to be caused by exogenous exposures, nor was any mutational signature capable of explaining differences in incidence rates between countries. These results suggest that the unexplained causes of pancreatic cancer are unlikely to be strongly mutagenic and that non-mutagenic mechanisms may have a prominent role in explaining pancreatic cancer incidence.
Source: medRxiv
Authors: Sarah Moody, Thomas Cattiaux, Jiali Pang, Haoran Zhang, Charles Nunn, Stephen Fitzgerald, Pilar Gallego-Garcia, Priscilia Chopard, Arash Nikmanesh, Valerie Gaborieau, Christine Carreira, Calli Latimer, Saamin Cheema, Sergey Senkin, Giovana Tardin Torrezan, Anh Phuong Le, Aida Ferreiro-Iglesias, Ilinca Lungu, Marcos Diaz-Gay, Stefano Serra, Rui Manuel Reis, Denise Peixoto Guimaraes, Patricia Ashton-Prolla, Alessandro Bersch Osvaldt, Andre de Moricz, Adhemar Monteiro Pacheco Junior, Maria Paula Curado, Felipe Jose Fernandez Coimbra, Vladimir Dugalic, Simona Ognjanovic, Tatsuhiro Shibata, Satoshi Shiba, Reza Malekzadeh, Saman Nikeghbalian, Ahmadreza Niavarani, Fatemeh Shafighian, Beata Swiatkowska, Janusz Strzelczyk, Katarzyna Roszkowska-Purska, Jolanta Lissowska, Ivana Holcatova, Pavel Zaruba, Anush Mukeria, Oksana Shangina, David Zaridze, Samuel O Antwi, Ann L Oberg, Steven Gallinger, Julie M Wilson, Ana Carolina de Carvalho, Laura Humphreys, Sandra Perdomo, Behnoush Abedi-Ardekani, Ludmil B Alexandrov, Paul Brennan, Michael R Stratton
Institutions: Wellcome Sanger Institute, World Health Organization, Centre international de recherche sur le cancer, University of California San Diego, Spanish National Cancer Research Centre, Tehran University of Medical Sciences, AC Camargo Hospital, Ontario Institute for Cancer Research, University of Toronto, Hospital de Câncer de Barretos, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, University of Belgrade, The University of Tokyo, National Cancer Center Research Institute, Shiraz University of Medical Sciences, Nofer Institute of Occupational Medicine, Medical University of Lodz, The Maria Sklodowska-Curie National Research Institute of Oncology, Charles University, Russian Cancer Research Center NN Blokhin, Mayo Clinic
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Awards: G1105844351, Structural and biophysical mechanism of microRNA nuclear export, G318412399, Wellcome Sanger Institute Quinquennial Review 2021-2026, G410571670, G451917667, G491712853, G4993905653, Wellcome Sanger Institute Quinquennial Review 2021-2026, G5539308778, G5635532810, G5967599077, G6520718613, G6571368241, G717256432, G7483984754, Wellcome Trust Sanger Institute - generic account for deposition of all core- funded research papers., G7805626310, G7863371703, G8497050386, G9000285489
OpenAlex ID: W7223275677