TY - JOUR
T1 - Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case–control approaches
AU - Gomez-Rubio, Paulina
AU - Piñero, Janet
AU - Molina-Montes, Esther
AU - Gutiérrez-Sacristán, Alba
AU - Marquez, Mirari
AU - Rava, Marta
AU - Michalski, Christoph W.
AU - Farré, Antoni
AU - Molero, Xavier
AU - Löhr, Matthias
AU - Perea, José
AU - Greenhalf, William
AU - O'Rorke, Michael
AU - Tardón, Adonina
AU - Gress, Thomas
AU - Barberá, Victor M.
AU - Crnogorac-Jurcevic, Tatjana
AU - Muñoz-Bellvís, Luís
AU - Domínguez-Muñoz, Enrique
AU - Balsells, Joaquim
AU - Costello, Eithne
AU - Yu, Jingru
AU - Iglesias, Mar
AU - Ilzarbe, Lucas
AU - Kleeff, Jörg
AU - Kong, Bo
AU - Mora, Josefina
AU - Murray, Liam
AU - O'Driscoll, Damian
AU - Poves, Ignasi
AU - Lawlor, Rita T.
AU - Ye, Weimin
AU - Hidalgo, Manuel
AU - Scarpa, Aldo
AU - Sharp, Linda
AU - Carrato, Alfredo
AU - Real, Francisco X.
AU - Furlong, Laura I.
AU - Malats, Núria
PY - 2019/4/1
Y1 - 2019/4/1
N2 - © 2018 UICC 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.
AB - © 2018 UICC 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.
KW - autoimmune diseases
KW - case–control study
KW - gene-disease associations
KW - genetic network
KW - multimorbidity
KW - pancreatic cancer risk
KW - Genetic Predisposition to Disease
KW - Humans
KW - Risk Factors
KW - Logistic Models
KW - Male
KW - Computational Biology/methods
KW - Pancreatic Neoplasms/epidemiology
KW - Case-Control Studies
KW - Europe/epidemiology
KW - Female
KW - Odds Ratio
KW - Autoimmune Diseases/epidemiology
KW - Gene Ontology
UR - http://www.mendeley.com/research/pancreatic-cancer-autoimmune-diseases-association-sustained-computational-epidemiological-casecontro
U2 - 10.1002/ijc.31866
DO - 10.1002/ijc.31866
M3 - Article
C2 - 30229903
SN - 0020-7136
VL - 144
SP - 1540
EP - 1549
JO - International Journal of Cancer
JF - International Journal of Cancer
ER -