A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk
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- dc.contributor.author Gomez-Rubio, P.ca
- dc.contributor.author Piñero González, Janet, 1977-ca
- dc.contributor.author Ilzarbe Sánchez, Lucasca
- dc.contributor.author Iglesias Coma, Marca
- dc.contributor.author Poves Prim, José Ignacioca
- dc.contributor.author Real, Francisco X.ca
- dc.contributor.author PanGenEU Study Investigators
- dc.date.accessioned 2017-11-16T08:58:50Z
- dc.date.issued 2017
- dc.description.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.
- dc.description.sponsorship The work was partially supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III-FEDER, Spain (PI11/01542, PI0902102, PI12/01635, PI12/00815, PI13/00082, and CP10/00524); Red Tematica de Investigacion Cooperativa en Cancer, Spain (RD12/0036/0034, RD12/0036/0050, and RD12/0036/0073); World Cancer Research (WCR 15-0391); Accion Especial de Gen omica, Spain (GEN2001-4748-c05-03); EU-6FP Integrated Project (018771-MOLDIAG-PACA), EUFP7-HEALTH (259737-CANCERALIA, 256974-EPC-TM-Net, and 602783-Cam-Pac), Associazione Italiana Ricerca sul Cancro (AIRC 12182); Cancer Focus Northern Ireland and Department for Employment and Learning; ALF (SLL20130022), Sweden; Italian Foundation for Cancer Research (FIRC) (no grant numbers apply). The
- dc.format.mimetype application/pdfca
- dc.identifier.citation Gomez-Rubio P, Rosato V, Márquez M, Bosetti C, Molina-Montes E, Rava M. et al. A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk. Ann Oncol. 2017 Jul 1;28(7):1618-24. DOI: 10.1093/annonc/mdx167
- dc.identifier.doi http://dx.doi.org/10.1093/annonc/mdx167
- dc.identifier.issn 0923-7534
- dc.identifier.uri http://hdl.handle.net/10230/33250
- dc.language.iso eng
- dc.publisher Oxford University Pressca
- dc.relation.ispartof Annals of Oncology. 2017 Jul 1;28(7):1618-24
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/259737
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/018771
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/256974
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/602783
- dc.rights © Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Annals of Oncology following peer review. The definitive publisher-authenticated version Gomez-Rubio P, Rosato V, Márquez M, Bosetti C, Molina-Montes E, Rava M. et al. A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk. Ann Oncol. 2017 Jul 1;28(7):1618-1624 is available online at: https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdx167
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.keyword Multimorbidity
- dc.subject.keyword Pancreatic cancer
- dc.subject.other Pàncrees -- Càncer
- dc.title A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer riskca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion