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Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk
Y. Lu, M. Gentiluomo, A. Macauda, D. Gioffreda, M. Gazouli, MC. Petrone, D. Kelemen, L. Ginocchi, L. Morelli, K. Papiris, W. Greenhalf, JR. Izbicki, V. Kiudelis, B. Mohelníková-Duchoňová, B. Bueno-de-Mesquita, P. Vodicka, H. Brenner, MK. Diener,...
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
NLK
Directory of Open Access Journals
od 2011
Free Medical Journals
od 2011
PubMed Central
od 2011
Europe PubMed Central
od 2011
Open Access Digital Library
od 2011-01-01
Open Access Digital Library
od 2011-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2011
PubMed
34926279
DOI
10.3389/fonc.2021.771312
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p<10-5) compared with the additive effects (p>10-3), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5×10-8). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.
1st Department of Medicine University of Szeged Szeged Hungary
1st Faculty of Medicine Institute of Biology and Medical Genetics Prague Czechia
Applied Research on Cancer Net Research Center University and Hospital Trust of Verona Verona Italy
Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czechia
Blood Transfusion Service Children's Hospital Azienda Ospedaliero Universitaria Meyer Florence Italy
Centre for Surgical Oncology Medias Klinikum Burghausen Burghausen Germany
Centre for Translational Medicine Department of Medicine University of Szeged Szeged Hungary
Department for Determinants of Chronic Diseases Bilthoven Netherlands
Department of Biology University of Pisa Pisa Italy
Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland
Department of General Surgery University of Heidelberg Heidelberg Germany
Department of Internal Medicine San Carlo Hospital Potenza Italy
Department of Medicine Padua University Hospital Padua Italy
Department of Radiology and Oncology Institute of Cancer of São Paulo São Paulo Brazil
Department of Surgery Medical School University of Pécs Pécs Hungary
Digestive and Liver Disease Unit Sant' Andrea Hospital Rome Italy
Division of General and Transplant Surgery Pisa University Hospital Pisa Italy
Division of Preventive Oncology German Cancer Research Center Heidelberg Germany
Endoscopic Surgery Department Hippocratio General Hospital of Athens Athens Greece
Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czechia
Faculty of Medicine and Psychology Sapienza University of Rome Rome Italy
Faculty of Medicine University of São Paulo São Paulo Brazil
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
German Cancer Consortium Heidelberg Germany
Institute for Translational Medicine Medical School University of Pécs Pécs Hungary
Laboratory for Applied Science and Technology in Health Carlos Chagas Institute Curitiba Brazil
Medical Faculty Heidelberg University of Heidelberg Heidelberg Germany
Citace poskytuje Crossref.org
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