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

Deciphering the underlying genetic basis behind pancreatic cancer PC and its associated multimorbidities will enhance our knowledge towards 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 this study, we report sound findings pointing to an association between AIDs and a reduced risk of PC. This article is protected by copyright. All rights reserved.