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

P. Gomez-Rubio, V. Rosato, M. Márquez, C. Bosetti, E. Molina-Montes, M. Rava, J. Piñero, C. W. Michalski, A. Farré, X. Molero, M. Löhr, L. Ilzarbe, J. Perea, W. Greenhalf, M. O'Rorke, A. Tardón, T. Gress, V. M. Barberá, T. Crnogorac-Jurcevic, L. Muñoz-BellvísE. Domínguez-Muñoz, A. Gutiérrez-Sacristán, J. Balsells, E. Costello, C. Guillén-Ponce, J. Huang, M. Iglesias, J. Kleeff, B. Kong, J. Mora, L. Murray, D. O'Driscoll, P. Peláez, I. Poves, R. T. Lawlor, A. Carrato, M. Hidalgo, A. Scarpa, L. Sharp, L. I. Furlong, F. X. Real, C. La Vecchia, N. Malats, PanGenEU Study Investigators

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1618-1624
Number of pages7
JournalAnnals of oncology : official journal of the European Society for Medical Oncology
Volume28
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

Keywords

  • multimorbidity
  • pancreatic cancer
  • risk

ASJC Scopus subject areas

  • Hematology
  • Oncology

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