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Int J Cancer. 2018 Sep 19. doi: 10.1002/ijc.31866. [Epub ahead of print]

Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches.

Author information

1
Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain.
2
Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
3
Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain.
4
Department of Surgery, Technical University of Munich, Munich, Germany.
5
Department of Surgery, University of Heidelberg, Heidelberg, Germany.
6
Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
7
Hospital Universitaru Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
8
Universitat Auntònoma de Barcelona, Campus de la UAB, Barcelona, Spain.
9
Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and University Hospital, Stockholm, Sweden.
10
Department of Surgery, University Hospital 12 de Octubre, Madrid, Spain.
11
Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, United Kingdom.
12
Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom.
13
Department of Medicine, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
14
Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany.
15
Laboratorio de Genética Molecular, Hospital General Universitario de Elche, Elche, Spain.
16
Centre for Molecular Oncology, John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
17
General and Digestive Surgery Department, Hospital Universitario de Salamanca, Salamanca, Spain.
18
Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
19
Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain.
20
Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, (Saale), Germany.
21
Cancer Data Registrars, National Cancer Registry Ireland, Cork, Ireland.
22
ARC-Net Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, University Hospital Trust of Verona, Verona, Italy.
23
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and University Hospital, Sweden.
24
Hospital Madrid-Norte-Sanchinarro and Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
25
Rosenberg Clinical Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
26
Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom.
27
Department of Oncology, Hospital Ramón y Cajal, Madrid, Spain.
28
Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
29
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
30
PanGenEU Study Investigators (Additional file 1: Annex S1).

Abstract

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.

KEYWORDS:

autoimmune diseases; case-control study; gene-disease associations; genetic network; multimorbidity; pancreatic cancer risk

PMID:
30229903
DOI:
10.1002/ijc.31866

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