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. 2023 Oct;55(10):1417-1425.
doi: 10.1016/j.dld.2023.02.023. Epub 2023 Mar 25.

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

Ylenia Nodari  1 , Manuel Gentiluomo  1 , Beatrice Mohelnikova-Duchonova  2 , Edita Kreivenaite  3 , Anna Caterina Milanetto  4 , Jurgita Skieceviciene  3 , Stefano Landi  1 , Rita T Lawlor  5 , Maria Chiara Petrone  6 , Paolo Giorgio Arcidiacono  6 , Martin Lovecek  7 , Maria Gazouli  8 , Maarten F Bijlsma  9 , Luca Morelli  10 , Vytautas Kiudelis  3 , Matteo Tacelli  6 , Dalila Lucíola Zanette  11 , Pavel Soucek  12 , Faik Uzunoglu  13 , Rudolf Kaaks  14 , Jakob Izbicki  13 , Ugo Boggi  15 , Raffaele Pezzilli  16 , Andrea Mambrini  17 , Claudio Pasquali  4 , Hanneke W van Laarhoven  18 , Verena Katzke  14 , Giulia Martina Cavestro  19 , Cosimo Sperti  20 , Martin Loos  21 , Anna Latiano  22 , Bálint Erőss  23 , Martin Oliverius  24 , Theron Johnson  14 , Daniela Basso  25 , John P Neoptolemos  21 , Mateus Nóbrega Aoki  11 , William Greenhalf  26 , Pavel Vodicka  27 , Livia Archibugi  28 , Giuseppe Vanella  28 , Maurizio Lucchesi  17 , Renata Talar-Wojnarowska  29 , Krzysztof Jamroziak  30 , Mohammed Al Saeedi  21 , Casper H J van Eijck  31 , Juozas Kupcinskas  3 , Tamás Hussein  32 , Marta Puzzono  19 , Stefania Bunduc  33 , Mara Götz  13 , Silvia Carrara  34 , Andrea Szentesi  35 , Francesca Tavano  22 , Stefania Moz  25 , Péter Hegyi  36 , Claudio Luchini  5 , Gabriele Capurso  28 , Francesco Perri  22 , Stefano Ermini  37 , George Theodoropoulos  38 , Giovanni Capretti  39 , Orazio Palmieri  22 , Laura Ginocchi  17 , Niccolò Furbetta  10 , Federico Canzian  40 , Daniele Campa  41
Affiliations
Free article

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

Ylenia Nodari et al. Dig Liver Dis. 2023 Oct.
Free article

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.

Keywords: Early onset; GWAS; Pancreatic cancer; Risk factor.

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Conflict of interest statement

Conflict of interest M.F.B. has received research funding from Celgene and Lead Pharma and acted as a consultant to Servier. H.W.M.L. reports research funding and/or medication supply from Bristol-Myers Squibb, Bayer Schering Pharma, Celgene, Janssen-Cilag, Lilly, Nordic Pharma, Philips Healthcare, Roche, Merck Sharp and Dohme, Servier, Incyte; and consultant/advisory board member for Lilly, Nordic Pharma, Bristol-Myers Squibb, Dragonfly, Merck Sharp and Dohme, Servier, all outside the submitted work. The other authors do not have any conflict of interest to declare.

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