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

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
Surgery
Internal medicine
Center of Experimental and Molecular Medicine
CCA - Cancer biology and immunology
CCA - Imaging and biomarkers
Oncology
CCA - Cancer Treatment and Quality of Life
AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Source :
Digestive and Liver Disease. Elsevier, Nodari, Y, Gentiluomo, M, Mohelnikova-Duchonova, B, Kreivenaite, E, Milanetto, A C, Skieceviciene, J, Landi, S, Lawlor, R T, Petrone, M C, Arcidiacono, P G, Lovecek, M, Gazouli, M, Bijlsma, M F, Morelli, L, Kiudelis, V, Tacelli, M, Zanette, D L, Soucek, P, Uzunoglu, F, Kaaks, R, Izbicki, J, Boggi, U, Pezzilli, R, Mambrini, A, Pasquali, C, van Laarhoven, H W, Katzke, V, Cavestro, G M, Sperti, C, Loos, M, Latiano, A, Erőss, B L, Oliverius, M, Johnson, T, Basso, D, Neoptolemos, J P, Aoki, M N B, Greenhalf, W, Vodicka, P, Archibugi, L, Vanella, G, Lucchesi, M, Talar-Wojnarowska, R, Jamroziak, K, Saeedi, M A, van Eijck, C H J, Kupcinskas, J, Hussein, T, Puzzono, M, Bunduc, S, Götz, M, Carrara, S, Szentesi, A, Tavano, F, Moz, S, Hegyi, P T, Luchini, C, Capurso, G, Perri, F, Ermini, S, Theodoropoulos, G, Capretti, G, Palmieri, O, Ginocchi, L, Furbetta, N, Canzian, F & Campa, D 2023, ' Genetic and non-genetic risk factors for early-onset pancreatic cancer ', Digestive and Liver Disease . https://doi.org/10.1016/j.dld.2023.02.023, Digestive and liver disease. Elsevier
Publication Year :
2023

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.

Details

Language :
English
ISSN :
15908658
Database :
OpenAIRE
Journal :
Digestive and Liver Disease. Elsevier, Nodari, Y, Gentiluomo, M, Mohelnikova-Duchonova, B, Kreivenaite, E, Milanetto, A C, Skieceviciene, J, Landi, S, Lawlor, R T, Petrone, M C, Arcidiacono, P G, Lovecek, M, Gazouli, M, Bijlsma, M F, Morelli, L, Kiudelis, V, Tacelli, M, Zanette, D L, Soucek, P, Uzunoglu, F, Kaaks, R, Izbicki, J, Boggi, U, Pezzilli, R, Mambrini, A, Pasquali, C, van Laarhoven, H W, Katzke, V, Cavestro, G M, Sperti, C, Loos, M, Latiano, A, Erőss, B L, Oliverius, M, Johnson, T, Basso, D, Neoptolemos, J P, Aoki, M N B, Greenhalf, W, Vodicka, P, Archibugi, L, Vanella, G, Lucchesi, M, Talar-Wojnarowska, R, Jamroziak, K, Saeedi, M A, van Eijck, C H J, Kupcinskas, J, Hussein, T, Puzzono, M, Bunduc, S, Götz, M, Carrara, S, Szentesi, A, Tavano, F, Moz, S, Hegyi, P T, Luchini, C, Capurso, G, Perri, F, Ermini, S, Theodoropoulos, G, Capretti, G, Palmieri, O, Ginocchi, L, Furbetta, N, Canzian, F & Campa, D 2023, ' Genetic and non-genetic risk factors for early-onset pancreatic cancer ', Digestive and Liver Disease . https://doi.org/10.1016/j.dld.2023.02.023, Digestive and liver disease. Elsevier
Accession number :
edsair.doi.dedup.....908b302f31600ad0c324d0be7a47532d