title: A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, and CIBERONC, Spain.
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mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D016000:Cluster Analysis; D015897:Comorbidity; D019295:Computational Biology; D030541:Databases, Genetic; D005060:Europe / Q000453:epidemiology; D005163:Factor Analysis, Statistical; D006801:Humans; D016015:Logistic Models; D015999:Multivariate Analysis; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D025341:Principal Component Analysis; D018570:Risk Assessment; D012307:Risk Factors; D013597:Systems Analysis; D049490:Systems Biology; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: multimorbidity; pancreatic cancer; risk