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POLYMORPHISMS IN TRANSCRIPTION FACTOR BINDING SITES AND ENHANCER REGIONS AND PANCREATIC DUCTAL ADENOCARCINOMA RISK
Pancreatic Neoplasms
Polymorphism, Single Nucleotide
Transcription Factors
Binding Sites
Neoplasias Pancreáticas
Polimorfismo de Nucleótido Simple
Factores de Transcripción
Sitios de Unión
Neoplasias Pancreáticas
Polimorfismo de Nucleotídeo Único
Fatores de Transcrição
Sítios de Ligação
Autor
Ünal, Pelin
Lu, Ye
Bueno‑de‑Mesquita, Bas
Eijck, Casper H. J. van
Talar‑Wojnarowska, Renata
Szentesi, Andrea
Gazouli, Maria
Kreivenaite, Edita
Tavano, Francesca
Małecka‑Wojciesko, Ewa
Erőss, Bálint
Oliverius, Martin
Bunduc, Stefania
Aoki, Mateus Nóbrega
Vodickova, Ludmila
Boggi, Ugo
Giaccherini, Matteo
Kondrackiene, Jurate
Chammas, Roger
Palmieri, Orazio
Theodoropoulos, George E.
Bijlsma, Maarten F.
Basso, Daniela
Mohelnikova‑Duchonova, Beatrice
Soucek, Pavel
Izbicki, Jakob R.
Kiudelis, Vytautas
Vanella, Giuseppe
Arcidiacono, Paolo Giorgio
Włodarczyk, Barbara
Hackert, Thilo
Schöttker, Ben
Uzunoglu, Faik G.
Bambi, Franco
Goetz, Mara
Hlavac, Viktor
Brenner, Hermann
Perri, Francesco
Carrara, Silvia
Landi, Stefano
Hegyi, Péter
Dijk, Frederike
Maiello, Evaristo
Capretti, Giovanni
Testoni, Sabrina Gloria Giulia
Petrone, Maria Chiara
Stocker, Hannah
Ermini, Stefano
Archibugi, Livia
Gentiluomo, Manuel
Cavestro, Giulia Martina
Pezzilli, Raffaele
Di Franco, Gregorio
Milanetto, Anna Caterina
Sperti, Cosimo
Neoptolemos, John P.
Morelli, Luca
Vokacova, Klara
Pasquali, Claudio
Lawlor, Rita T.
Bazzocchi, Francesca
Kupcinskas, Juozas
Capurso, Gabriele
Campa, Daniele
Canzian, Federico
Lu, Ye
Bueno‑de‑Mesquita, Bas
Eijck, Casper H. J. van
Talar‑Wojnarowska, Renata
Szentesi, Andrea
Gazouli, Maria
Kreivenaite, Edita
Tavano, Francesca
Małecka‑Wojciesko, Ewa
Erőss, Bálint
Oliverius, Martin
Bunduc, Stefania
Aoki, Mateus Nóbrega
Vodickova, Ludmila
Boggi, Ugo
Giaccherini, Matteo
Kondrackiene, Jurate
Chammas, Roger
Palmieri, Orazio
Theodoropoulos, George E.
Bijlsma, Maarten F.
Basso, Daniela
Mohelnikova‑Duchonova, Beatrice
Soucek, Pavel
Izbicki, Jakob R.
Kiudelis, Vytautas
Vanella, Giuseppe
Arcidiacono, Paolo Giorgio
Włodarczyk, Barbara
Hackert, Thilo
Schöttker, Ben
Uzunoglu, Faik G.
Bambi, Franco
Goetz, Mara
Hlavac, Viktor
Brenner, Hermann
Perri, Francesco
Carrara, Silvia
Landi, Stefano
Hegyi, Péter
Dijk, Frederike
Maiello, Evaristo
Capretti, Giovanni
Testoni, Sabrina Gloria Giulia
Petrone, Maria Chiara
Stocker, Hannah
Ermini, Stefano
Archibugi, Livia
Gentiluomo, Manuel
Cavestro, Giulia Martina
Pezzilli, Raffaele
Di Franco, Gregorio
Milanetto, Anna Caterina
Sperti, Cosimo
Neoptolemos, John P.
Morelli, Luca
Vokacova, Klara
Pasquali, Claudio
Lawlor, Rita T.
Bazzocchi, Francesca
Kupcinskas, Juozas
Capurso, Gabriele
Campa, Daniele
Canzian, Federico
Afiliación
Genomic Epidemiology Group. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Genomic Epidemiology Group. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Department for Determinants of Chronic Diseases (DCD). National Institute for Public Health and the Environment (RIVM). Bilthoven, Netherlands.
Department of Surgery. Erasmus MC University Medical Center. Rotterdam, the Netherlands.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary.
Laboratory of Biology. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / Centre for Translational Medicine. Semmelweis University. Budapest, Hungary. / Division of Pancreatic Diseases. Heart and Vascular Center. Semmelweis University. Budapest, Hungary.
Department of Surgery. University Hospital Kralovske Vinohrady. Third Faculty of Medicine Charles University. Prague, Czech Republic.
Centre 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.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologias Aplicadas em Saúde. Curitiba, PR, Brasil.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic. / Department of Molecular Biology of Cancer. Institute of Experimental Medicine of the Czech Academy of Sciences. Prague, Czechia. / Institute of Biology and Medical Genetics. Institute of Physiology. First Faculty of Medicine. Charles University. Prague, Czech Republic.
Division of General and Transplant Surgery. Pisa University Hospital. Pisa, Italy.
Department of Biology. University of Pisa. Pisa, Italy.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Instituto do Cancer de São Paulo. Departamento de Radiologia e Oncologia. São Paulo, SP, Brasil.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
First Propaedeutic University Surgery Clinic. Hippocratio General Hospital. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
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.
Department of Medicine. Laboratory Medicine. University of Padova. Padua, Italy.
Department of Oncology. Faculty of Medicine and Dentistry. Palacky University Olomouc. Olomouc, Czechia.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic.
Department of General Visceral and Thoracic Surgery. University of Hamburg Medical Institutions. Hamburg, Germany.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy. / Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Department of General, Visceral and Transplant Surgery. Heidelberg University Hospital. Heidelberg, Germany.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Network Aging Research (NAR). Heidelberg University. Heidelberg, Germany.
Department of General Visceral and Thoracic Surgery. University of Hamburg Medical Institutions. Hamburg, Germany.
Blood Transfusion Service. Meyer Children’s Hospital. Florence, Italy.
Department of General Visceral and Thoracic Surgery. University of Hamburg Medical Institutions. Hamburg, Germany.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic.
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 (DKFZ). Heidelberg, Germany.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
Department of Gastroenterology. Endoscopic Unit. IRCCS Humanitas Research Hospital. Milan, Italy.
Department of Biology. University of Pisa. Pisa, Italy.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / János Szentágothai Research Center. University of Pécs. Pécs, Hungary. / Centre for Translational Medicine. Semmelweis University. Budapest, Hungary. / Division of Pancreatic Diseases. Heart and Vascular Center. Semmelweis University. Budapest, Hungary.
Department of Pathology. Cancer Center Amsterdam. Amsterdam University Medical Centers. University of Amsterdam. Amsterdam, Netherlands.
Department of Oncology. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo. Foggia, Italy.
Pancreatic Surgery Unit. IRCCS Humanitas Research Hospital. Milan, Italy. / Department of Biomedical Sciences. Humanitas University. Milan, Italy.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Network Aging Research (NAR). Heidelberg University. Heidelberg, Germany.
Blood Transfusion Service. Meyer Children’s Hospital. Florence, Italy.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy. / Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy.
Department of Biology. University of Pisa. Pisa, Italy.
Gastroenterology and Gastrointestinal Endoscopy Unit. IRCCS San Raffaele Scientific Institute. Vita-Salute San Raffaele University. Milan, Italy.
Department of Gastroenterology. San Carlo Hospital. Potenza, Italy.
General Surgery Unit. Department of Translational Research and New Technologies in Medicine and Surgery. University of Pisa. Pisa, Italy.
Department of Surgery, Oncology and Gastroenterology. University of Padova. Padua, Italy.
Department of Surgery, Oncology and Gastroenterology. University of Padova. Padua, Italy.
Department of General, Visceral and Transplant Surgery. Heidelberg University Hospital. Heidelberg, Germany.
General Surgery Unit. Department of Translational Research and New Technologies in Medicine and Surgery. University of Pisa. Pisa, Italy.
Department of Molecular Biology of Cancer. Institute of Experimental Medicine of the Czech Academy of Sciences. Prague, Czechia. / Institute of Biology and Medical Genetics. Institute of Physiology. First Faculty of Medicine. Charles University. Prague, Czech Republic.
Department of Surgery, Oncology and Gastroenterology. University of Padova. Padua, Italy.
Department of Diagnostics and Public Health. ARC‑Net Centre for Applied Research on Cancer. University of Verona. Verona, Italy.
Department of Surgery. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo. FG, Italy.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy. / Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy.
Department of Biology. University of Pisa. Pisa, Italy.
Genomic Epidemiology Group. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Genomic Epidemiology Group. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Department for Determinants of Chronic Diseases (DCD). National Institute for Public Health and the Environment (RIVM). Bilthoven, Netherlands.
Department of Surgery. Erasmus MC University Medical Center. Rotterdam, the Netherlands.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary.
Laboratory of Biology. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / Centre for Translational Medicine. Semmelweis University. Budapest, Hungary. / Division of Pancreatic Diseases. Heart and Vascular Center. Semmelweis University. Budapest, Hungary.
Department of Surgery. University Hospital Kralovske Vinohrady. Third Faculty of Medicine Charles University. Prague, Czech Republic.
Centre 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.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologias Aplicadas em Saúde. Curitiba, PR, Brasil.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic. / Department of Molecular Biology of Cancer. Institute of Experimental Medicine of the Czech Academy of Sciences. Prague, Czechia. / Institute of Biology and Medical Genetics. Institute of Physiology. First Faculty of Medicine. Charles University. Prague, Czech Republic.
Division of General and Transplant Surgery. Pisa University Hospital. Pisa, Italy.
Department of Biology. University of Pisa. Pisa, Italy.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Instituto do Cancer de São Paulo. Departamento de Radiologia e Oncologia. São Paulo, SP, Brasil.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
First Propaedeutic University Surgery Clinic. Hippocratio General Hospital. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
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.
Department of Medicine. Laboratory Medicine. University of Padova. Padua, Italy.
Department of Oncology. Faculty of Medicine and Dentistry. Palacky University Olomouc. Olomouc, Czechia.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic.
Department of General Visceral and Thoracic Surgery. University of Hamburg Medical Institutions. Hamburg, Germany.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy. / Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Department of General, Visceral and Transplant Surgery. Heidelberg University Hospital. Heidelberg, Germany.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Network Aging Research (NAR). Heidelberg University. Heidelberg, Germany.
Department of General Visceral and Thoracic Surgery. University of Hamburg Medical Institutions. Hamburg, Germany.
Blood Transfusion Service. Meyer Children’s Hospital. Florence, Italy.
Department of General Visceral and Thoracic Surgery. University of Hamburg Medical Institutions. Hamburg, Germany.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic.
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 (DKFZ). Heidelberg, Germany.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
Department of Gastroenterology. Endoscopic Unit. IRCCS Humanitas Research Hospital. Milan, Italy.
Department of Biology. University of Pisa. Pisa, Italy.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / János Szentágothai Research Center. University of Pécs. Pécs, Hungary. / Centre for Translational Medicine. Semmelweis University. Budapest, Hungary. / Division of Pancreatic Diseases. Heart and Vascular Center. Semmelweis University. Budapest, Hungary.
Department of Pathology. Cancer Center Amsterdam. Amsterdam University Medical Centers. University of Amsterdam. Amsterdam, Netherlands.
Department of Oncology. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo. Foggia, Italy.
Pancreatic Surgery Unit. IRCCS Humanitas Research Hospital. Milan, Italy. / Department of Biomedical Sciences. Humanitas University. Milan, Italy.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Network Aging Research (NAR). Heidelberg University. Heidelberg, Germany.
Blood Transfusion Service. Meyer Children’s Hospital. Florence, Italy.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy. / Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy.
Department of Biology. University of Pisa. Pisa, Italy.
Gastroenterology and Gastrointestinal Endoscopy Unit. IRCCS San Raffaele Scientific Institute. Vita-Salute San Raffaele University. Milan, Italy.
Department of Gastroenterology. San Carlo Hospital. Potenza, Italy.
General Surgery Unit. Department of Translational Research and New Technologies in Medicine and Surgery. University of Pisa. Pisa, Italy.
Department of Surgery, Oncology and Gastroenterology. University of Padova. Padua, Italy.
Department of Surgery, Oncology and Gastroenterology. University of Padova. Padua, Italy.
Department of General, Visceral and Transplant Surgery. Heidelberg University Hospital. Heidelberg, Germany.
General Surgery Unit. Department of Translational Research and New Technologies in Medicine and Surgery. University of Pisa. Pisa, Italy.
Department of Molecular Biology of Cancer. Institute of Experimental Medicine of the Czech Academy of Sciences. Prague, Czechia. / Institute of Biology and Medical Genetics. Institute of Physiology. First Faculty of Medicine. Charles University. Prague, Czech Republic.
Department of Surgery, Oncology and Gastroenterology. University of Padova. Padua, Italy.
Department of Diagnostics and Public Health. ARC‑Net Centre for Applied Research on Cancer. University of Verona. Verona, Italy.
Department of Surgery. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo. FG, Italy.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Pancreato Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute. Milan, Italy. / Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy.
Department of Biology. University of Pisa. Pisa, Italy.
Genomic Epidemiology Group. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Resumen en ingles
Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratifcation and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict signifcance 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 profle 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 identifed four associations that reached study-wide statistical signifcance 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 signifcant 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.
Palabras clave en ingles
Genome-Wide Association StudyPancreatic Neoplasms
Polymorphism, Single Nucleotide
Transcription Factors
Binding Sites
Palabras clave
Estudio de Asociación del Genoma CompletoNeoplasias Pancreáticas
Polimorfismo de Nucleótido Simple
Factores de Transcripción
Sitios de Unión
DeCS
Estudo de Associação Genômica AmplaNeoplasias Pancreáticas
Polimorfismo de Nucleotídeo Único
Fatores de Transcrição
Sítios de Ligação
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