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Lookup NU author(s): Professor Linda Sharp
This is the authors' accepted manuscript of an article that has been published in its final definitive form by John Wiley & Sons, Inc., 2019.
For re-use rights please refer to the publisher's terms and conditions.
© 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.
Author(s): Gomez-Rubio P, Pinero J, Molina-Montes E, Gutierrez-Sacristan A, Marquez M, Rava M, Michalski CW, Farre A, Molero X, Lohr M, Perea J, Greenhalf W, O'Rorke M, Tardon A, Gress T, Barbera VM, Crnogorac-Jurcevic T, Munoz-Bellvis L, Dominguez-Munoz 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
Publication type: Article
Publication status: Published
Journal: International Journal of Cancer
Year: 2019
Volume: 144
Issue: 7
Pages: 1540-1549
Print publication date: 01/04/2019
Online publication date: 19/09/2018
Acceptance date: 27/07/2018
Date deposited: 19/06/2020
ISSN (print): 0020-7136
ISSN (electronic): 1097-0215
Publisher: John Wiley & Sons, Inc.
URL: https://doi.org/10.1002/ijc.31866
DOI: 10.1002/ijc.31866
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