A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk


Gomez-Rubio, P, Rosato, V, Marquez, M, Bosetti, C, Molina-Montes, E, Rava, M, Pinero, J, Michalski, CW, Farre, A, Molero, X et al (show 33 more authors) (2017) A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk. ANNALS OF ONCOLOGY, 28 (7). pp. 1618-1624.

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Abstract

<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients.<h4>Methods</h4>Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases.<h4>Results</h4>Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis.<h4>Conclusions</h4>Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

Item Type: Article
Uncontrolled Keywords: pancreatic cancer, multimorbidity, risk
Depositing User: Symplectic Admin
Date Deposited: 21 May 2020 09:15
Last Modified: 19 Jan 2023 00:54
DOI: 10.1093/annonc/mdx167
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3036173
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