Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
32591343
DOI
10.1136/jmedgenet-2020-106961
PII: jmedgenet-2020-106961
Knihovny.cz E-zdroje
- Klíčová slova
- genetic epidemiology, oncology, pancreas and biliary tract,
- MeSH
- ABO systém krevních skupin genetika MeSH
- alely MeSH
- časná detekce nádoru MeSH
- duktální karcinom slinivky břišní diagnóza genetika MeSH
- frekvence genu MeSH
- hodnocení rizik MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- multifaktoriální dědičnost * MeSH
- nádory slinivky břišní genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABO systém krevních skupin MeSH
BACKGROUND: Most cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection. OBJECTIVE: We generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score. METHODS: We tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes. RESULTS: The scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10-10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10-8, highest vs lowest quintile of the weighted multifactorial score). CONCLUSION: We found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.
1st Department of Medicine University of Szeged Szeged Hungary
Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Biomedical Centre Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Cancer Center Amsterdam Amsterdam The Netherlands
Cancer Epidemiology Unit Nuffield Department of Population Health University of Oxford Oxford UK
Department of Biology University of Pisa Pisa Italy
Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland
Department of Gastroenterology Polyclinic of Sant'Orsola Bologna Italy
Department of Hematology Institute of Hematology and Transfusion Medicine Warsaw Poland
Department of Interventional Gastroenterology National Institute of Oncology Budapest Hungary
Department of Laboratory Medicine University Hospital of Padova Padova Italy
Department of Medical Oncology Amsterdam UMC University of Amsterdam Amsterdam The Netherlands
Department of Surgical Oncology and HPB Surgery University of Cyprus Nicosia Cyprus
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of General and Transplant Surgery Pisa University Hospital Pisa Italy
Division of Preventive Oncology German Cancer Research Center Heidelberg Germany
General and Pancreatic Surgery Department Pancreas Institute University of Verona Verona Italy
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
German Cancer Consortium Heidelberg Heidelberg Germany
Institute for Translational Medicine Medical School University of Pécs Pécs Hungary
Laboratory of Biology Medical School National and Kapodistrian University of Athens Athens Greece
Network Aging Research University of Heidelberg Heidelberg Germany
Pancreatic and Endocrine Surgical Unit University of Padova Padova Italy
Saarland Cancer Registry Saarbrücken Germany
Szent György University Teaching Hospital of Fejér County Székesfehérvár Hungary
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