Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches
Por:
Gomez-Rubio P, Piñero J, Molina-Montes E, Gutiérrez-Sacristán A, Marquez M, Rava M, Michalski CW, Farré A, Molero X, Löhr M, Perea J, Greenhalf W, O'Rorke M, Tardón A, Gress T, Barbera V, Crnogorac-Jurcevic T, Muñoz-Bellvís L, Domínguez-Muñoz E, Balsells J, Costello E, Yu J, Iglesias M, Ilzarbe L, Kleeff J, Kong B, Mora J, Murray L, O'Driscoll D, Poves I, Lawlor RT, Ye W, Hidalgo M, Scarpa A, Sharp L, Carrato A, Real FX, Furlong LI, Malats N and PanGenEU Study Investigators
Publicada:
1 abr 2019
Resumen:
Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene-disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case-control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58-0.93) which decreased in subjects having >= 2 AIDs (OR = 0.39, 95%CI 0.21-0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19-0.89, and OR = 0.73, 95%CI 0.53-1.00, respectively). Several inflammatory-related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC.
Filiaciones:
Gomez-Rubio P:
Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Piñero J:
Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain
Molina-Montes E:
Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Gutiérrez-Sacristán A:
Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain
Marquez M:
Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Rava M:
Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Michalski CW:
Department of Surgery, Technical University of Munich, Munich, Germany
Department of Surgery, University of Heidelberg, Heidelberg, Germany
Farré A:
Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Molero X:
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Hospital Universitaru Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
Universitat Auntònoma de Barcelona, Campus de la UAB, Barcelona, Spain
Löhr M:
Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and University Hospital, Stockholm, Sweden
Perea J:
Department of Surgery, University Hospital 12 de Octubre, Madrid, Spain
Greenhalf W:
Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, United Kingdom
O'Rorke M:
Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
Tardón A:
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Department of Medicine, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain
Gress T:
Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany
Barbera V:
Laboratorio de Genética Molecular, Hospital General Universitario de Elche, Elche, Spain
Crnogorac-Jurcevic T:
Centre for Molecular Oncology, John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
Muñoz-Bellvís L:
General and Digestive Surgery Department, Hospital Universitario de Salamanca, Salamanca, Spain
Domínguez-Muñoz E:
Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
Balsells J:
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Hospital Universitaru Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
Universitat Auntònoma de Barcelona, Campus de la UAB, Barcelona, Spain
Costello E:
Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, United Kingdom
Yu J:
Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and University Hospital, Stockholm, Sweden
Iglesias M:
Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain
Ilzarbe L:
Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain
Kleeff J:
Department of Surgery, Technical University of Munich, Munich, Germany
Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, (Saale), Germany
Kong B:
Department of Surgery, Technical University of Munich, Munich, Germany
Mora J:
Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Murray L:
Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
O'Driscoll D:
Cancer Data Registrars, National Cancer Registry Ireland, Cork, Ireland
Poves I:
Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain
Lawlor RT:
ARC-Net Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, University Hospital Trust of Verona, Verona, Italy
Ye W:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and University Hospital, Sweden
Hidalgo M:
Hospital Madrid-Norte-Sanchinarro and Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Rosenberg Clinical Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Scarpa A:
ARC-Net Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, University Hospital Trust of Verona, Verona, Italy
Sharp L:
Cancer Data Registrars, National Cancer Registry Ireland, Cork, Ireland
Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom
Carrato A:
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Department of Oncology, Hospital Ramón y Cajal, Madrid, Spain
Real FX:
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
Furlong LI:
Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain
Malats N:
Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
PanGenEU Study Investigators:
PanGenEU Study Investigators (Additional file 1: Annex S1)
Green Submitted, Green Published
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