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Article

PubMed

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

Digestive and liver disease. 2023 Oct ; 55 (10) : 1417-1425. [epub] 20230325

Dig Liver Dis
ISSN 1878-3562 | 1590-8658
Source

Language English Country Netherlands Media print-electronic

Document type Journal Article

Persistent link https://www.medvik.cz/link/pmid36973108

Grant support
MR/M012190/1 Medical Research Council - United Kingdom

PubMed 36973108
DOI 10.1016/j.dld.2023.02.023
PII: S1590-8658(23)00514-5
Knihovny.cz E-resources

Keywords
Early onset, GWAS, Pancreatic cancer, Risk factor,
MeSH
Genome-Wide Association Study MeSH
Diabetes Mellitus, Type 2 * epidemiology genetics complications MeSH
Carcinoma, Pancreatic Ductal * genetics pathology MeSH
Humans MeSH
Pancreatic Neoplasms * pathology MeSH
Risk Factors MeSH
Check Tag
Humans MeSH
Publication type
Journal Article MeSH

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.

1st Department of Propaedeutic Surgery Hippokration General Hospital of Athens School of Medicine National and Kapodistrian University of Athens Athens Greece

Blood Transfusion Service Children's Hospital Azienda Ospedaliero Universitaria Meyer Florence Italy

Carol Davila University of Medicine and Pharmacy Bucharest Romania; Center for Translational Medicine Semmelweis University Budapest Hungary; Division of Pancreatic Diseases Heart and Vascular Center Semmelweis University Budapest Hungary

Center for Experimental and Molecular Medicine Laboratory for Experimental Oncology and Radiobiology Amsterdam UMC location University of Amsterdam Amsterdam The Netherlands; Imaging and Biomarkers Cancer Center Amsterdam Amsterdam The Netherlands

Center for Translational Medicine Semmelweis University Budapest Hungary; Division of Pancreatic Diseases Heart and Vascular Center Semmelweis University Budapest Hungary

Country Medical Association of Potenza Potenza Italy

Department of Biology University of Pisa Pisa Italy

Department of Diagnostics and Public Health and ARC Net Research Centre University of Verona Verona Italy

Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland

Department of General Surgery University Hospital Kralovske Vinohrady 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of General Visceral and Thoracic Surgery University Medical Center Hamburg Eppendorf Hamburg Germany

Department of General Visceral and Transplantation Surgery University Hospital Heidelberg Heidelberg Germany