Year: 2023
Type: article
Study design: Observational Study
Abstract: Background Early-onset pancreatic cancer (EOPC) represents 5–10% of all pancreatic ductal adenocarcinoma (PDAC) cases, and the etiology of this form is poorly understood. It is not clear if established PDAC risk factors have the same relevance for younger patients. This study aims to identify genetic and non-genetic risk factors specific to EOPC. Methods A genome-wide association study was performed, analysing 912 EOPC cases and 10 222 controls, divided into discovery and replication phases. Furthermore, the associations between a polygenic risk score (PRS), smoking, alcohol consumption, type 2 diabetes and PDAC risk were also assessed. Results Six novel SNPs were associated with EOPC risk in the discovery phase, but not in the replication phase. The PRS, smoking, and diabetes affected EOPC risk. The OR comparing current smokers to never-smokers was 2.92 (95% CI 1.69–5.04, P = 1.44 × 10 −4 ). For diabetes, the corresponding OR was 14.95 (95% CI 3.41–65.50, P = 3.58 × 10 −4 ). Conclusion In conclusion, we did not identify novel genetic variants associated specifically with EOPC, and we found that established PDAC risk variants do not have a strong age-dependent effect. Furthermore, we add to the evidence pointing to the role of smoking and diabetes in EOPC.
Source: Digestive and Liver Disease
Authors: Ylenia Nodari, Manuel Gentiluomo, Beatrice Mohelnikova-Duchonova, Edita Kreivenaite, Anna Caterina Milanetto, Jurgita Skieceviciene, Stefano Landi, Rita T Lawlor, Maria Chiara Petrone, Paolo Giorgio Arcidiacono, Martin Lovecek, Maria Gazouli, Maarten F. Bijlsma, Luca Morelli, Vytautas Kiudelis, Matteo Tacelli, Dalila Lucíola Zanette, Pavel Soucek, Faik Uzunoglu, Rudolf Kaaks, Jakob Izbicki, Ugo Boggi, Raffaele Pezzilli, Andrea Mambrini, Claudio Pasquali, Hanneke W. van Laarhoven, Verena Katzke, Giulia Martina Cavestro, Cosimo Sperti, Martin Loos, Anna Latiano, Bálint Erőss, Martin Oliverius, Theron Johnson, Daniela Basso, John P. Neoptolemos, Mateus Nóbrega Aoki, William Greenhalf, Pavel Vodicka, Livia Archibugi, Giuseppe Vanella, Maurizio Lucchesi, Renata Talar-Wojnarowska, Krzysztof Jamroziak, Mohammed Al Saeedi, Casper H.J. van Eijck, Juozas Kupcinskas, Tamás Hussein, Marta Puzzono, Stefania Bunduc, Mara Götz, Silvia Carrara, Andrea Szentesi, Francesca Tavano, Stefania Moz, Péter Hegyi, Claudio Luchini, Gabriele Capurso, Francesco Perri, Stefano Ermini, George Theodoropoulos, Giovanni Capretti, Orazio Palmieri, Laura Ginocchi, Niccolò Furbetta, Federico Canzian, Daniele Campa
Institutions: University of Pisa, Palacký University Olomouc, Lithuanian University of Health Sciences, University of Padua, University of Verona, Vita-Salute San Raffaele University, University Hospital Olomouc, National and Kapodistrian University of Athens, Amsterdam UMC Location University of Amsterdam, Cancer Center Amsterdam, University of Amsterdam, Fundação Oswaldo Cruz, Charles University, University Medical Center Hamburg-Eppendorf, German Cancer Research Center, Azienda USL Toscana Nord Ovest, Amsterdam University Medical Centers, IRCCS Ospedale San Raffaele, University Hospital Heidelberg, Casa Sollievo della Sofferenza, Semmelweis University, University of Pecs, University Hospital Kralovske Vinohrady, University of Liverpool, Czech Academy of Sciences, Czech Academy of Sciences, Institute of Experimental Medicine, Azienda Ospedaliera Sant'Andrea, Istituti di Ricovero e Cura a Carattere Scientifico, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, Sapienza University of Rome, Medical University of Lodz, Medical University of Warsaw, Erasmus MC, Carol Davila University of Medicine and Pharmacy, IRCCS Humanitas Research Hospital, University of Szeged, Meyer Children's Hospital, Hippocration General Hospital, Humanitas University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,300
Funders: Cancer Research UK, European Cooperation in Science and Technology, Universität Heidelberg, Ministerstvo Školství, Mládeže a Tělovýchovy, Universiteit Utrecht, Ministero della Salute, Associazione Italiana per la Ricerca sul Cancro, Agentura Pro Zdravotnický Výzkum České Republiky, Fondazione Arpa, National Institutes of Health, Medical Research Council, European Regional Development Fund
Awards: G1192877484, G1937805885, G2076520454, G2715567343, G3216658785, G3328679326, G3667869120, G384027954, G4041385912, G4507020007, Health of vegetarians, G4844208673, G4879533352, G4980140004, G6085534252, G6176207898, G6442500046, G6820515600, G7478572479, G7642051084, G8082441536, G817390530, G992475775
OpenAlex ID: W4360944705