Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Autor: Ünal P; Genomic Epidemiology Group, German Cancer Research Center, In Neuenheimer Feld 280, 69120, Heidelberg, Germany., Lu Y; Genomic Epidemiology Group, German Cancer Research Center, In Neuenheimer Feld 280, 69120, Heidelberg, Germany., Bueno-de-Mesquita B; Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, Bilthoven, The Netherlands., van Eijck CHJ; Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Talar-Wojnarowska R; Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland., Szentesi A; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Gazouli M; Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Kreivenaite E; Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania., Tavano F; Division of Gastroenterology and Research Laboratory, Fondazione IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo, FG, Italy., Małecka-Wojciesko E; Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland., Erőss B; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.; Center for Translational Medicine, Semmelweis University, Budapest, Hungary.; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary., Oliverius M; Department of Surgery, University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic., Bunduc S; Center for Translational Medicine, Semmelweis University, Budapest, Hungary.; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania., Nóbrega Aoki M; Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Curitiba, PR, Brazil., Vodickova L; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Plzeň, Czech Republic.; Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.; Institute of Biology and Medical Genetics, Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic., Boggi U; Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy., Giaccherini M; Department of Biology, University of Pisa, Pisa, Italy., Kondrackiene J; Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania., Chammas R; Department of Radiology and Oncology, Institute of Cancer of São Paulo, São Paulo, Brazil., Palmieri O; Division of Gastroenterology and Research Laboratory, Fondazione IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo, FG, Italy., Theodoropoulos GE; First Propaedeutic University Surgery Clinic, Hippocratio General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Bijlsma MF; Laboratory for Experimental Oncology and Radiobiology, Center of Experimental Molecular Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands., Basso D; Department of Medicine, Laboratory Medicine, University of Padova, Padua, Italy., Mohelnikova-Duchonova B; Department of Oncology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic., Soucek P; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Plzeň, Czech Republic., Izbicki JR; Department of General Visceral and Thoracic Surgery, University of Hamburg Medical Institutions, Hamburg, Germany., Kiudelis V; Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania., Vanella G; PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy.; Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy., Arcidiacono PG; PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy., Włodarczyk B; Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland., Hackert T; Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Heidelberg, Germany., Schöttker B; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.; Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany., Uzunoglu FG; Department of General Visceral and Thoracic Surgery, University of Hamburg Medical Institutions, Hamburg, Germany., Bambi F; Blood Transfusion Service, Meyer Children's Hospital, Florence, Italy., Goetz M; Department of General Visceral and Thoracic Surgery, University of Hamburg Medical Institutions, Hamburg, Germany., Hlavac V; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Plzeň, Czech Republic., Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.; Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany.; Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center, Heidelberg, Germany., Perri F; Division of Gastroenterology and Research Laboratory, Fondazione IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo, FG, Italy., Carrara S; Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy., Landi S; Department of Biology, University of Pisa, Pisa, Italy., Hegyi P; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.; János Szentágothai Research Center, University of Pécs, Pécs, Hungary.; Center for Translational Medicine, Semmelweis University, Budapest, Hungary.; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary., Dijk F; Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Maiello E; Department of Oncology, Fondazione IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo, FG, Italy., Capretti G; Pancreatic Unit, IRCCS Humanitas Research Hospital, Milan, Italy.; Department of Biomedical Sciences, Humanitas University, Milan, Italy., Testoni SGG; PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy., Petrone MC; PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy., Stocker H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.; Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany., Ermini S; Blood Transfusion Service, Meyer Children's Hospital, Florence, Italy., Archibugi L; PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy.; Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy., Gentiluomo M; Department of Biology, University of Pisa, Pisa, Italy., Cavestro GM; Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy., Pezzilli R; Department of Gastroenterology, San Carlo Hospital, Potenza, Italy., Di Franco G; General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy., Milanetto AC; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy., Sperti C; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy., Neoptolemos JP; Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Heidelberg, Germany., Morelli L; General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy., Vokacova K; Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.; Institute of Biology and Medical Genetics, Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic., Pasquali C; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy., Lawlor RT; Department of Diagnostics and Public Health, ARC-Net Centre for Applied Research on Cancer, University of Verona, Verona, Italy., Bazzocchi F; Department of Surgery, Fondazione IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo, FG, Italy., Kupcinskas J; Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania., Capurso G; PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy.; Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy., Campa D; Department of Biology, University of Pisa, Pisa, Italy., Canzian F; Genomic Epidemiology Group, German Cancer Research Center, In Neuenheimer Feld 280, 69120, Heidelberg, Germany. f.canzian@dkfz.de.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2024 Feb 02; Vol. 18 (1), pp. 12. Date of Electronic Publication: 2024 Feb 02.
DOI: 10.1186/s40246-024-00576-x
Abstrakt: Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10 -8 ), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10 -7 ), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10 -6 ) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10 -5 ). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.
(© 2024. The Author(s).)
Databáze: MEDLINE
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