Genetic and non-genetic risk factors for early-onset pancreatic cancer

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 gene...

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Hauptverfasser: Nodari, Ylenia (VerfasserIn) , Gentiluomo, Manuel (VerfasserIn) , Mohelnikova-Duchonova, Beatrice (VerfasserIn) , Kreivenaite, Edita (VerfasserIn) , Milanetto, Anna Caterina (VerfasserIn) , Skieceviciene, Jurgita (VerfasserIn) , Landi, Stefano (VerfasserIn) , Lawlor, Rita T (VerfasserIn) , Petrone, Maria Chiara (VerfasserIn) , Arcidiacono, Paolo Giorgio (VerfasserIn) , Lovecek, Martin (VerfasserIn) , Gazouli, Maria (VerfasserIn) , Bijlsma, Maarten F. (VerfasserIn) , Morelli, Luca (VerfasserIn) , Kiudelis, Vytautas (VerfasserIn) , Tacelli, Matteo (VerfasserIn) , Zanette, Dalila Lucíola (VerfasserIn) , Soucek, Pavel (VerfasserIn) , Uzunoglu, Faik (VerfasserIn) , Kaaks, Rudolf (VerfasserIn) , Izbicki, Jakob (VerfasserIn) , Boggi, Ugo (VerfasserIn) , Pezzilli, Raffaele (VerfasserIn) , Mambrini, Andrea (VerfasserIn) , Pasquali, Claudio (VerfasserIn) , van Laarhoven, Hanneke W. (VerfasserIn) , Katzke, Verena (VerfasserIn) , Cavestro, Giulia Martina (VerfasserIn) , Sperti, Cosimo (VerfasserIn) , Loos, Martin (VerfasserIn) , Latiano, Anna (VerfasserIn) , Erőss, Bálint (VerfasserIn) , Oliverius, Martin (VerfasserIn) , Johnson, Theron S. (VerfasserIn) , Basso, Daniela (VerfasserIn) , Neoptolemos, John P. (VerfasserIn) , Aoki, Mateus Nóbrega (VerfasserIn) , Greenhalf, William (VerfasserIn) , Vodicka, Pavel (VerfasserIn) , Archibugi, Livia (VerfasserIn) , Vanella, Giuseppe (VerfasserIn) , Lucchesi, Maurizio (VerfasserIn) , Talar-Wojnarowska, Renata (VerfasserIn) , Jamroziak, Krzysztof (VerfasserIn) , Saeedi, Mohammed al (VerfasserIn) , van Eijck, Casper H. J. (VerfasserIn) , Kupcinskas, Juozas (VerfasserIn) , Hussein, Tamás (VerfasserIn) , Puzzono, Marta (VerfasserIn) , Bunduc, Stefania (VerfasserIn) , Götz, Mara (VerfasserIn) , Carrara, Silvia (VerfasserIn) , Szentesi, Andrea (VerfasserIn) , Tavano, Francesca (VerfasserIn) , Moz, Stefania (VerfasserIn) , Hegyi, Péter (VerfasserIn) , Luchini, Claudio (VerfasserIn) , Capurso, Gabriele (VerfasserIn) , Perri, Francesco (VerfasserIn) , Ermini, Stefano (VerfasserIn) , Theodoropoulos, George (VerfasserIn) , Capretti, Giovanni (VerfasserIn) , Palmieri, Orazio (VerfasserIn) , Ginocchi, Laura (VerfasserIn) , Furbetta, Niccolò (VerfasserIn) , Canzian, Federico (VerfasserIn) , Campa, Daniele (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: October 2023
In: Digestive and liver disease
Year: 2023, Jahrgang: 55, Heft: 10, Pages: 1417-1425
ISSN:1878-3562
DOI:10.1016/j.dld.2023.02.023
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.dld.2023.02.023
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1590865823005145
Volltext
Verfasserangaben: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

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245 1 0 |a Genetic and non-genetic risk factors for early-onset pancreatic cancer  |c 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 
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520 |a 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. 
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SRT |a NODARIYLENGENETICAND2023