-
Je něco špatně v tomto záznamu ?
Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk
P. Ünal, Y. Lu, B. Bueno-de-Mesquita, CHJ. van Eijck, R. Talar-Wojnarowska, A. Szentesi, M. Gazouli, E. Kreivenaite, F. Tavano, E. Małecka-Wojciesko, B. Erőss, M. Oliverius, S. Bunduc, M. Nóbrega Aoki, L. Vodickova, U. Boggi, M. Giaccherini, J....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
LX22NPO5102
National Institute for Cancer Research - NICR (Programme EXCELES)
LX22NPO5102
National Institute for Cancer Research - NICR (Programme EXCELES)
LX22NPO5102
National Institute for Cancer Research - NICR (Programme EXCELES)
LX22NPO5102
National Institute for Cancer Research - NICR (Programme EXCELES)
LX22NPO5102
National Institute for Cancer Research - NICR (Programme EXCELES)
NLK
BioMedCentral
od 2003-12-01
BioMedCentral Open Access
od 2003
Directory of Open Access Journals
od 2003
Free Medical Journals
od 2003
PubMed Central
od 2003
ProQuest Central
od 2003-11-01
Open Access Digital Library
od 2003-01-01
Open Access Digital Library
od 2003-01-01
Medline Complete (EBSCOhost)
od 2003-11-01
Health & Medicine (ProQuest)
od 2003-11-01
ROAD: Directory of Open Access Scholarly Resources
od 2003
Springer Nature OA/Free Journals
od 2003-12-01
- MeSH
- celogenomová asociační studie MeSH
- duktální karcinom slinivky břišní * genetika patologie MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- nádory slinivky břišní * genetika epidemiologie patologie MeSH
- regulační oblasti nukleových kyselin MeSH
- transkripční faktory genetika metabolismus MeSH
- vazebná místa genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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.
Biomedical Center Faculty of Medicine in Pilsen Charles University Plzeň Czech Republic
Blood Transfusion Service Meyer Children's Hospital Florence Italy
Cancer Center Amsterdam Imaging and Biomarkers Amsterdam the Netherlands
Carol Davila University of Medicine and Pharmacy Bucharest Romania
Center for Translational Medicine Semmelweis University Budapest Hungary
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 Gastroenterology San Carlo Hospital Potenza Italy
Department of Medicine Laboratory Medicine University of Padova Padua Italy
Department of Oncology Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic
Department of Radiology and Oncology Institute of Cancer of São Paulo São Paulo Brazil
Department of Surgery Erasmus MC University Medical Center Rotterdam The Netherlands
Department of Surgery Oncology and Gastroenterology University of Padova Padua Italy
Digestive and Liver Disease Unit S Andrea Hospital Rome Italy
Division of General and Transplant Surgery Pisa University Hospital Pisa Italy
Division of Pancreatic Diseases Heart and Vascular Center Semmelweis University Budapest Hungary
Endoscopic Unit Department of Gastroenterology IRCCS Humanitas Research Hospital Milan Italy
German Cancer Consortium German Cancer Research Center Heidelberg Germany
Institute for Translational Medicine Medical School University of Pécs Pécs Hungary
János Szentágothai Research Center University of Pécs Pécs Hungary
Laboratory for Applied Science and Technology in Health Carlos Chagas Institute Curitiba PR Brazil
Laboratory of Biology Medical School National and Kapodistrian University of Athens Athens Greece
Network Aging Research Heidelberg University Heidelberg Germany
Pancreatic Unit IRCCS Humanitas Research Hospital Milan Italy
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24007212
- 003
- CZ-PrNML
- 005
- 20240423155809.0
- 007
- ta
- 008
- 240412s2024 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1186/s40246-024-00576-x $2 doi
- 035 __
- $a (PubMed)38308339
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Ünal, Pelin $u Genomic Epidemiology Group, German Cancer Research Center, In Neuenheimer Feld 280, 69120, Heidelberg, Germany
- 245 10
- $a Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk / $c P. Ünal, Y. Lu, B. Bueno-de-Mesquita, CHJ. van Eijck, R. Talar-Wojnarowska, A. Szentesi, M. Gazouli, E. Kreivenaite, F. Tavano, E. Małecka-Wojciesko, B. Erőss, M. Oliverius, S. Bunduc, M. Nóbrega Aoki, L. Vodickova, U. Boggi, M. Giaccherini, J. Kondrackiene, R. Chammas, O. Palmieri, GE. Theodoropoulos, MF. Bijlsma, D. Basso, B. Mohelnikova-Duchonova, P. Soucek, JR. Izbicki, V. Kiudelis, G. Vanella, PG. Arcidiacono, B. Włodarczyk, T. Hackert, B. Schöttker, FG. Uzunoglu, F. Bambi, M. Goetz, V. Hlavac, H. Brenner, F. Perri, S. Carrara, S. Landi, P. Hegyi, F. Dijk, E. Maiello, G. Capretti, SGG. Testoni, MC. Petrone, H. Stocker, S. Ermini, L. Archibugi, M. Gentiluomo, GM. Cavestro, R. Pezzilli, G. Di Franco, AC. Milanetto, C. Sperti, JP. Neoptolemos, L. Morelli, K. Vokacova, C. Pasquali, RT. Lawlor, F. Bazzocchi, J. Kupcinskas, G. Capurso, D. Campa, F. Canzian
- 520 9_
- $a 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.
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a celogenomová asociační studie $7 D055106
- 650 _2
- $a genetická predispozice k nemoci $7 D020022
- 650 12
- $a nádory slinivky břišní $x genetika $x epidemiologie $x patologie $7 D010190
- 650 12
- $a duktální karcinom slinivky břišní $x genetika $x patologie $7 D021441
- 650 _2
- $a regulační oblasti nukleových kyselin $7 D012045
- 650 _2
- $a jednonukleotidový polymorfismus $x genetika $7 D020641
- 650 _2
- $a transkripční faktory $x genetika $x metabolismus $7 D014157
- 650 _2
- $a vazebná místa $x genetika $7 D001665
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Lu, Ye $u Genomic Epidemiology Group, German Cancer Research Center, In Neuenheimer Feld 280, 69120, Heidelberg, Germany
- 700 1_
- $a Bueno-de-Mesquita, Bas $u Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
- 700 1_
- $a van Eijck, Casper H J $u Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
- 700 1_
- $a Talar-Wojnarowska, Renata $u Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
- 700 1_
- $a Szentesi, Andrea $u Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- 700 1_
- $a Gazouli, Maria $u Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- 700 1_
- $a Kreivenaite, Edita $u Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- 700 1_
- $a Tavano, Francesca $u Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy
- 700 1_
- $a Małecka-Wojciesko, Ewa $u Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
- 700 1_
- $a Erőss, Bálint $u Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary $u Center for Translational Medicine, Semmelweis University, Budapest, Hungary $u Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
- 700 1_
- $a Oliverius, Martin $u Department of Surgery, University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Bunduc, Stefania $u Center for Translational Medicine, Semmelweis University, Budapest, Hungary $u Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary $u Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- 700 1_
- $a Nóbrega Aoki, Mateus $u Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Curitiba, PR, Brazil
- 700 1_
- $a Vodickova, Ludmila $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Plzeň, Czech Republic $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic $u Institute of Biology and Medical Genetics, Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Boggi, Ugo $u Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy
- 700 1_
- $a Giaccherini, Matteo $u Department of Biology, University of Pisa, Pisa, Italy
- 700 1_
- $a Kondrackiene, Jurate $u Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- 700 1_
- $a Chammas, Roger $u Department of Radiology and Oncology, Institute of Cancer of São Paulo, São Paulo, Brazil
- 700 1_
- $a Palmieri, Orazio $u Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy
- 700 1_
- $a Theodoropoulos, George E $u First Propaedeutic University Surgery Clinic, Hippocratio General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- 700 1_
- $a Bijlsma, Maarten F $u Laboratory for Experimental Oncology and Radiobiology, Center of Experimental Molecular Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands $u Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands
- 700 1_
- $a Basso, Daniela $u Department of Medicine, Laboratory Medicine, University of Padova, Padua, Italy
- 700 1_
- $a Mohelnikova-Duchonova, Beatrice $u Department of Oncology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
- 700 1_
- $a Soucek, Pavel $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Plzeň, Czech Republic
- 700 1_
- $a Izbicki, Jakob R $u Department of General Visceral and Thoracic Surgery, University of Hamburg Medical Institutions, Hamburg, Germany
- 700 1_
- $a Kiudelis, Vytautas $u Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- 700 1_
- $a Vanella, Giuseppe $u PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy $u Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy
- 700 1_
- $a Arcidiacono, Paolo Giorgio $u PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
- 700 1_
- $a Włodarczyk, Barbara $u Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
- 700 1_
- $a Hackert, Thilo $u Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Heidelberg, Germany
- 700 1_
- $a Schöttker, Ben $u Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany $u Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany
- 700 1_
- $a Uzunoglu, Faik G $u Department of General Visceral and Thoracic Surgery, University of Hamburg Medical Institutions, Hamburg, Germany
- 700 1_
- $a Bambi, Franco $u Blood Transfusion Service, Meyer Children's Hospital, Florence, Italy
- 700 1_
- $a Goetz, Mara $u Department of General Visceral and Thoracic Surgery, University of Hamburg Medical Institutions, Hamburg, Germany
- 700 1_
- $a Hlavac, Viktor $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Plzeň, Czech Republic
- 700 1_
- $a Brenner, Hermann $u Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany $u Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany $u Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany $u German Cancer Consortium (DKTK), German Cancer Research Center, Heidelberg, Germany
- 700 1_
- $a Perri, Francesco $u Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy
- 700 1_
- $a Carrara, Silvia $u Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
- 700 1_
- $a Landi, Stefano $u Department of Biology, University of Pisa, Pisa, Italy
- 700 1_
- $a Hegyi, Péter $u Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary $u János Szentágothai Research Center, University of Pécs, Pécs, Hungary $u Center for Translational Medicine, Semmelweis University, Budapest, Hungary $u Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
- 700 1_
- $a Dijk, Frederike $u Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- 700 1_
- $a Maiello, Evaristo $u Department of Oncology, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy
- 700 1_
- $a Capretti, Giovanni $u Pancreatic Unit, IRCCS Humanitas Research Hospital, Milan, Italy $u Department of Biomedical Sciences, Humanitas University, Milan, Italy
- 700 1_
- $a Testoni, Sabrina Gloria Giulia $u PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
- 700 1_
- $a Petrone, Maria Chiara $u PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
- 700 1_
- $a Stocker, Hannah $u Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany $u Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany
- 700 1_
- $a Ermini, Stefano $u Blood Transfusion Service, Meyer Children's Hospital, Florence, Italy
- 700 1_
- $a Archibugi, Livia $u PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy $u Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy
- 700 1_
- $a Gentiluomo, Manuel $u Department of Biology, University of Pisa, Pisa, Italy
- 700 1_
- $a Cavestro, Giulia Martina $u Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
- 700 1_
- $a Pezzilli, Raffaele $u Department of Gastroenterology, San Carlo Hospital, Potenza, Italy
- 700 1_
- $a Di Franco, Gregorio $u General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- 700 1_
- $a Milanetto, Anna Caterina $u Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
- 700 1_
- $a Sperti, Cosimo $u Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
- 700 1_
- $a Neoptolemos, John P $u Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Heidelberg, Germany
- 700 1_
- $a Morelli, Luca $u General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- 700 1_
- $a Vokacova, Klara $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic $u Institute of Biology and Medical Genetics, Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Pasquali, Claudio $u Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
- 700 1_
- $a Lawlor, Rita T $u Department of Diagnostics and Public Health, ARC-Net Centre for Applied Research on Cancer, University of Verona, Verona, Italy
- 700 1_
- $a Bazzocchi, Francesca $u Department of Surgery, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy
- 700 1_
- $a Kupcinskas, Juozas $u Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- 700 1_
- $a Capurso, Gabriele $u PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy $u Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy
- 700 1_
- $a Campa, Daniele $u Department of Biology, University of Pisa, Pisa, Italy
- 700 1_
- $a Canzian, Federico $u Genomic Epidemiology Group, German Cancer Research Center, In Neuenheimer Feld 280, 69120, Heidelberg, Germany. f.canzian@dkfz.de
- 773 0_
- $w MED00008733 $t Human genomics $x 1479-7364 $g Roč. 18, č. 1 (2024), s. 12
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/38308339 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20240412 $b ABA008
- 991 __
- $a 20240423155805 $b ABA008
- 999 __
- $a ok $b bmc $g 2081291 $s 1216979
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 18 $c 1 $d 12 $e 20240202 $i 1479-7364 $m Human genomics $n Hum Genomics $x MED00008733
- GRA __
- $a LX22NPO5102 $p National Institute for Cancer Research - NICR (Programme EXCELES)
- GRA __
- $a LX22NPO5102 $p National Institute for Cancer Research - NICR (Programme EXCELES)
- GRA __
- $a LX22NPO5102 $p National Institute for Cancer Research - NICR (Programme EXCELES)
- GRA __
- $a LX22NPO5102 $p National Institute for Cancer Research - NICR (Programme EXCELES)
- GRA __
- $a LX22NPO5102 $p National Institute for Cancer Research - NICR (Programme EXCELES)
- LZP __
- $a Pubmed-20240412
