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Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case–control approaches
Author(s) -
GomezRubio Paulina,
Piñero Janet,
MolinaMontes Esther,
GutiérrezSacristán Alba,
Marquez Mirari,
Rava Marta,
Michalski Christoph W.,
Farré Antoni,
Molero Xavier,
Löhr Matthias,
Perea José,
Greenhalf William,
O'Rorke Michael,
Tardón Adonina,
Gress Thomas,
Barberá Victor M.,
CrnogoracJurcevic Tatjana,
MuñozBellvís Luís,
DomínguezMuñoz Enrique,
Balsells Joaquim,
Costello Eithne,
Yu Jingru,
Iglesias Mar,
Ilzarbe Lucas,
Kleeff Jörg,
Kong Bo,
Mora Josefina,
Murray Liam,
O'Driscoll Damian,
Poves Ignasi,
Lawlor Rita T.,
Ye Weimin,
Hidalgo Manuel,
Scarpa Aldo,
Sharp Linda,
Carrato Alfredo,
Real Francisco X.,
Furlong Laura I.,
Malats Núria
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31866
Subject(s) - odds ratio , epidemiology , medicine , polymyalgia rheumatica , case control study , population , confidence interval , rheumatoid arthritis , logistic regression , cancer , oncology , disease , immunology , vasculitis , environmental health , giant cell arteritis
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.