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

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-g...

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Bibliographic Details
Main Authors: Nodari Ylenia
Gentiluomo Manuel
Mohelnikova-Duchonova Beatrice
Kreivenaite Edita
Milanetto Anna Caterina
Skieceviciene Jurgita
Landi Stefano
Lawlor Rita T.
Petrone Maria Chiara
Erőss Bálint Mihály
Hussein Tamás
Bunduc Stefania
Szentesi Andrea Ildikó
Hegyi Péter
et al
Format: Article
Published: 2023
Series:DIGESTIVE AND LIVER DISEASE 55 No. 10
Subjects:
doi:10.1016/j.dld.2023.02.023

mtmt:33727941
Online Access:http://publicatio.bibl.u-szeged.hu/26912
Description
Summary: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.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.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).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.
Physical Description:1417-1425
ISSN:1590-8658