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https://www.arca.fiocruz.br/handle/icict/56103
COMMON VARIABILITY IN OESTROGEN‑RELATED GENES AND PANCREATIC DUCTAL ADENOCARCINOMA RISK IN WOMEN
Factores de Riesgo
Polimorfismo de Nucleótido Simple
Author
Peduzzi, Giulia
Archibugi, Livia
Katzke, Verena
Gentiluomo, Manuel
Capurso, Gabriele
Milanetto, Anna Caterina
Gazouli, Maria
Goetz, Mara
Brenner, Hermann
Vermeulen, Roel C. H.
Talar‑Wojnarowska, Renata
Vanella, Giuseppe
Tavano, Francesca
Lucchesi, Maurizio
Mohelnikova‑Duchonova, Beatrice
Chen, Xuechen
Kiudelis, Vytautas
Hegyi, Péter
Oliverius, Martin
Stocker, Hannah
Stornello, Caterina
Vodickova, Ludmila
Souček, Pavel
Neoptolemos, John P.
Testoni, Sabrina Gloria Giulia
Morelli, Luca
Lawlor, Rita T.
Basso, Daniela
Izbicki, Jakob R.
Ermini, Stefano
Kupcinskas, Juozas
Pezzilli, Raffaele
Boggi, Ugo
Laarhoven, Hanneke W. M. van
Szentesi, Andrea
Erőss, Bálint
Capretti, Giovanni
Schöttker, Ben
Skieceviciene, Jurgita
Aoki, Mateus Nóbrega
Eijck, Casper H. J. van
Cavestro, Giulia Martina
Canzian, Federico
Campa, Daniele
Archibugi, Livia
Katzke, Verena
Gentiluomo, Manuel
Capurso, Gabriele
Milanetto, Anna Caterina
Gazouli, Maria
Goetz, Mara
Brenner, Hermann
Vermeulen, Roel C. H.
Talar‑Wojnarowska, Renata
Vanella, Giuseppe
Tavano, Francesca
Lucchesi, Maurizio
Mohelnikova‑Duchonova, Beatrice
Chen, Xuechen
Kiudelis, Vytautas
Hegyi, Péter
Oliverius, Martin
Stocker, Hannah
Stornello, Caterina
Vodickova, Ludmila
Souček, Pavel
Neoptolemos, John P.
Testoni, Sabrina Gloria Giulia
Morelli, Luca
Lawlor, Rita T.
Basso, Daniela
Izbicki, Jakob R.
Ermini, Stefano
Kupcinskas, Juozas
Pezzilli, Raffaele
Boggi, Ugo
Laarhoven, Hanneke W. M. van
Szentesi, Andrea
Erőss, Bálint
Capretti, Giovanni
Schöttker, Ben
Skieceviciene, Jurgita
Aoki, Mateus Nóbrega
Eijck, Casper H. J. van
Cavestro, Giulia Martina
Canzian, Federico
Campa, Daniele
Affilliation
Department of Biology. University of Pisa, Pisa, Italy.
Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy. / Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
Division of Cancer Epidemiology. German Cancer Research Center. Heidelberg, Germany.
Department of Biology. University of Pisa, Pisa, Italy.
Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy. / Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
Department DISCOG. University of Padova. Padua, Italy.
Laboratory of Biology. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
Department of General. Visceral and Thoracic Surgery. University Medical Center Hamburg Eppendorf. Hamburg, Germany.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Division of Preventive Oncology. German Cancer Research Center and National Center for Tumor Diseases. Heidelberg, Germany. / German Cancer Consortium. German Cancer Research Center. Heidelberg, Germany.
University of Utrecht. Utrecht, The Netherlands.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy. / Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
Oncology of Massa Carrara. Oncological Department. Azienda USL Toscana Nord Ovest. Carrara, Italy.
Department of Oncology. Faculty of Medicine and Dentistry. Palacký University Olomouc. Olomouc, Czech Republic.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Medical Faculty Heidelberg. Heidelberg University. Heidelberg, Germany.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
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. / János Szentágothai Research Center. University of Pécs. Pécs, Hungary.
Surgery Clinic Third Faculty of Medicine. Charles University. Prague, Czech Republic.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Network Aging Research. Heidelberg University. Heidelberg, Germany.
Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy. / Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
Department of Molecular Biology of Cancer. Institute of Experimental Medicine of the Czech Academy of Sciences. Prague, Czechia. / First Faculty of Medicine. Institute of Biology and Medical Genetics. Charles University. Prague, Czech Republic. / Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
General Surgery. Department of Translational Research and New Technologies in Medicine and Surgery. University of Pisa. Pisa, Italy.
ARC‑NET. Centre for Applied Research on Cancer. University and Hospital Trust of Verona. Verona, Italy.
Department DIMED‑Laboratory Medicine. University of Padova. Padua, Italy.
Department of General. Visceral and Thoracic Surgery. University Medical Center Hamburg Eppendorf. Hamburg, Germany.
Blood Transfusion Service. Azienda Ospedaliero-Universitaria Meyer. Florence, Italy.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Potenza Medical County Association. Potenza, Italy.
Division of General and Transplant Surgery. Pisa University Hospital. Pisa, Italy.
Department of Medical Oncology. Amsterdam UMC Location University of Amsterdam. Amsterdam, Netherlands. / Cancer Center Amsterdam. Imaging and Biomarkers. Amsterdam, The Netherlands.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / János Szentágothai Research Center. University of Pécs. Pécs, Hungary. / Centre for Translational Medicine. Department of Medicine. University of Szeged. Szeged, Hungary.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / Division of Pancreatic Diseases. Heart and Vascular Center. Semmelweis University. Budapest, Hungary. / Centre for Translational Medicine. Semmelweis University. Budapest, Hungary.
Department of Biomedical Sciences. Humanitas University. Milan, Italy. / Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologias Aplicadas em Saúde. Curitiba, PR, Brasil.
Department of Surgery. Erasmus MC University Medical Center. Rotterdam, The Netherlands.
Gastroenterology and Gastrointestinal Endoscopy Unit. Vita-Salute San Raffaele University. IRCCS San Raffaele Scientific Institute. Milan, Italy.
Genomic Epidemiology Group. German Cancer Research Center. Heidelberg, Germany.
Department of Biology. University of Pisa, Pisa, Italy.
Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy. / Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
Division of Cancer Epidemiology. German Cancer Research Center. Heidelberg, Germany.
Department of Biology. University of Pisa, Pisa, Italy.
Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy. / Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
Department DISCOG. University of Padova. Padua, Italy.
Laboratory of Biology. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
Department of General. Visceral and Thoracic Surgery. University Medical Center Hamburg Eppendorf. Hamburg, Germany.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Division of Preventive Oncology. German Cancer Research Center and National Center for Tumor Diseases. Heidelberg, Germany. / German Cancer Consortium. German Cancer Research Center. Heidelberg, Germany.
University of Utrecht. Utrecht, The Netherlands.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy. / Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
Oncology of Massa Carrara. Oncological Department. Azienda USL Toscana Nord Ovest. Carrara, Italy.
Department of Oncology. Faculty of Medicine and Dentistry. Palacký University Olomouc. Olomouc, Czech Republic.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Medical Faculty Heidelberg. Heidelberg University. Heidelberg, Germany.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
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. / János Szentágothai Research Center. University of Pécs. Pécs, Hungary.
Surgery Clinic Third Faculty of Medicine. Charles University. Prague, Czech Republic.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany. / Network Aging Research. Heidelberg University. Heidelberg, Germany.
Digestive and Liver Disease Unit. Sant’Andrea Hospital. Rome, Italy. / Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
Department of Molecular Biology of Cancer. Institute of Experimental Medicine of the Czech Academy of Sciences. Prague, Czechia. / First Faculty of Medicine. Institute of Biology and Medical Genetics. Charles University. Prague, Czech Republic. / Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czech Republic.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
Pancreato‑Biliary Endoscopy and Endoscopic Ultrasound. Pancreas Translational and Clinical Research Center. San Raffaele Scientific Institute IRCCS. Milan, Italy.
General Surgery. Department of Translational Research and New Technologies in Medicine and Surgery. University of Pisa. Pisa, Italy.
ARC‑NET. Centre for Applied Research on Cancer. University and Hospital Trust of Verona. Verona, Italy.
Department DIMED‑Laboratory Medicine. University of Padova. Padua, Italy.
Department of General. Visceral and Thoracic Surgery. University Medical Center Hamburg Eppendorf. Hamburg, Germany.
Blood Transfusion Service. Azienda Ospedaliero-Universitaria Meyer. Florence, Italy.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Potenza Medical County Association. Potenza, Italy.
Division of General and Transplant Surgery. Pisa University Hospital. Pisa, Italy.
Department of Medical Oncology. Amsterdam UMC Location University of Amsterdam. Amsterdam, Netherlands. / Cancer Center Amsterdam. Imaging and Biomarkers. Amsterdam, The Netherlands.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / János Szentágothai Research Center. University of Pécs. Pécs, Hungary. / Centre for Translational Medicine. Department of Medicine. University of Szeged. Szeged, Hungary.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / Division of Pancreatic Diseases. Heart and Vascular Center. Semmelweis University. Budapest, Hungary. / Centre for Translational Medicine. Semmelweis University. Budapest, Hungary.
Department of Biomedical Sciences. Humanitas University. Milan, Italy. / Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center. Heidelberg, Germany.
Gastroenterology Department and Institute for Digestive Research. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologias Aplicadas em Saúde. Curitiba, PR, Brasil.
Department of Surgery. Erasmus MC University Medical Center. Rotterdam, The Netherlands.
Gastroenterology and Gastrointestinal Endoscopy Unit. Vita-Salute San Raffaele University. IRCCS San Raffaele Scientific Institute. Milan, Italy.
Genomic Epidemiology Group. German Cancer Research Center. Heidelberg, Germany.
Department of Biology. University of Pisa, Pisa, Italy.
Abstract
The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes (NR5A2, MED1, NCOA2 and RUNX1) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10− 5) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk.
Keywords in Portuguese
Variantes do gene NR5A2Keywords in Spanish
Carcinoma Ductal PancreáticoFactores de Riesgo
Polimorfismo de Nucleótido Simple
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