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Genetic and non-genetic risk factors for early-onset pancreatic cancer
Y. Nodari, M. Gentiluomo, B. Mohelnikova-Duchonova, E. Kreivenaite, AC. Milanetto, J. Skieceviciene, S. Landi, RT. Lawlor, MC. Petrone, PG. Arcidiacono, M. Lovecek, M. Gazouli, MF. Bijlsma, L. Morelli, V. Kiudelis, M. Tacelli, DL. Zanette, P....
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články
- MeSH
- celogenomová asociační studie MeSH
- diabetes mellitus 2. typu * epidemiologie genetika komplikace MeSH
- duktální karcinom slinivky břišní * genetika patologie MeSH
- lidé MeSH
- nádory slinivky břišní * patologie MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články 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.
Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
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
Centre for Translational Medicine Department of Medicine University of Szeged Szeged Hungary
Country Medical Association of Potenza Potenza Italy
Department of Biology University of Pisa Pisa Italy
Department of Biomedical Sciences Humanitas University Milan Italy
Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland
Department of Medicine DIMED Laboratory Medicine University of Padova Padova Italy
Department of Oncology Faculty of Medicine and Dentistry Palacký University Olomouc Czech Republic
Department of Surgery 1 University Hospital Olomouc Olomouc Czech Republic
Department of Surgery Erasmus MC University Medical Center Rotterdam the Netherlands
Dept of Surgery Oncology and Gastroenterology University of Padova Chirurgia Generale 3 Padova Italy
Digestive and Liver Disease Unit S Andrea Hospital Sapienza University of Rome Rome Italy
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of Pancreatic Diseases Heart and Vascular Center Semmelweis University Budapest Hungary
Divisione di Chirurgia Generale e dei Trapianti Università di Pisa Pisa Italy
Endoscopic Unit Department of Gastroenterology IRCCS Humanitas Research Hospital Rozzano Italy
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
Imaging and Biomarkers Cancer Center Amsterdam Amsterdam The Netherlands
Institute for Translational Medicine Medical School University of Pécs Pécs Hungary
János Szentágothai Research Center University of Pécs Pécs Hungary
Molecular and Clinical Cancer Medicine The University of Liverpool Liverpool United Kingdom
Oncological Department Massa Carrara Azienda USL Toscana Nord Ovest Carrara Italy
Pancreatic Unit IRCCS Humanitas Research Hospital Rozzano Italy
Citace poskytuje Crossref.org
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- $a Nodari, Ylenia $u Department of Biology, University of Pisa, Pisa, Italy
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- $a Genetic and non-genetic risk factors for early-onset pancreatic cancer / $c Y. Nodari, M. Gentiluomo, B. Mohelnikova-Duchonova, E. Kreivenaite, AC. Milanetto, J. Skieceviciene, S. Landi, RT. Lawlor, MC. Petrone, PG. Arcidiacono, M. Lovecek, M. Gazouli, MF. Bijlsma, L. Morelli, V. Kiudelis, M. Tacelli, DL. Zanette, P. Soucek, F. Uzunoglu, R. Kaaks, J. Izbicki, U. Boggi, R. Pezzilli, A. Mambrini, C. Pasquali, HW. van Laarhoven, V. Katzke, GM. Cavestro, C. Sperti, M. Loos, A. Latiano, B. Erőss, M. Oliverius, T. Johnson, D. Basso, JP. Neoptolemos, MN. Aoki, W. Greenhalf, P. Vodicka, L. Archibugi, G. Vanella, M. Lucchesi, R. Talar-Wojnarowska, K. Jamroziak, MA. Saeedi, CHJ. van Eijck, J. Kupcinskas, T. Hussein, M. Puzzono, S. Bunduc, M. Götz, S. Carrara, A. Szentesi, F. Tavano, S. Moz, P. Hegyi, C. Luchini, G. Capurso, F. Perri, S. Ermini, G. Theodoropoulos, G. Capretti, O. Palmieri, L. Ginocchi, N. Furbetta, F. Canzian, D. Campa
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- $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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