Journal article
A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk
Annals of oncology, Vol.28(7), pp.1618-1624
07/01/2017
DOI: 10.1093/annonc/mdx167
PMID: 28383714
Abstract
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.
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.
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.
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.
Details
- Title: Subtitle
- A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk
- Creators
- P Gomez-Rubio - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, and CIBERONC, SpainV Rosato - Unit of Medical Statistics, Biometry and Bioinformatics, National Cancer Institute, IRCCS Foundation, MilanM Márquez - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, and CIBERONC, SpainC Bosetti - Department of Epidemiology, Mario Negri Institute for Pharmacological Research-IRCCS, Milan, ItalyE Molina-Montes - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, and CIBERONC, SpainM Rava - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, and CIBERONC, SpainJ Piñero - Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Pompeu Fabra Univeristy (UPF), Barcelona, SpainC W Michalski - Department of Surgery, University of Heidelberg, Heidelberg, GermanyA Farré - Department of Gastroenterology, Santa Creu i Sant Pau Hospital, BarcelonaX Molero - Network of Biomedical Research Centres (CIBER), Hepatic and Digestive Diseases and Epidemiology and Public Health, Madrid, SpainM Löhr - Gastrocentrum, Karolinska Institutet and University Hospital, Stockholm, SwedenL Ilzarbe - Department of Gastroenterology, Parc de Salut Mar University Hospital, BarcelonaJ Perea - Department of Surgery, 12 de Octubre University Hospital, Madrid, SpainW Greenhalf - Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, LiverpoolM O'Rorke - Centre for Public Health, Queen's University Belfast, Belfast, UKA Tardón - Department of Medicine, University Institute of Oncology of Asturias, Oviedo, SpainT Gress - Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, GermanyV M Barberá - Molecular Genetics Laboratory, General University Hospital of Elche, Elche, SpainT Crnogorac-Jurcevic - Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, UKL Muñoz-Bellvís - General and Digestive Surgery Department, Salamanca University Hospital, SalamancaE Domínguez-Muñoz - Department of Gastroenterology, Clinical University Hospital of Santiago de Compostela, Santiago de CompostelaA Gutiérrez-Sacristán - Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Pompeu Fabra Univeristy (UPF), Barcelona, SpainJ Balsells - Network of Biomedical Research Centres (CIBER), Hepatic and Digestive Diseases and Epidemiology and Public Health, Madrid, SpainE Costello - Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, LiverpoolC Guillén-Ponce - Department of Oncology, Ramón y Cajal Hospital, Madrid, and CIBERONC, SpainM Iglesias - Department of Gastroenterology, Parc de Salut Mar University Hospital, BarcelonaJ Kleeff - Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, LiverpoolB Kong - Department of Surgery, Technical University of Munich, MunichJ Mora - Department of Gastroenterology, Santa Creu i Sant Pau Hospital, BarcelonaL Murray - Centre for Public Health, Queen's University Belfast, Belfast, UKD O'Driscoll - Research Programme, National Cancer Registry IrelandP Peláez - Department of Surgery, 12 de Octubre University Hospital, Madrid, SpainI Poves - Department of Gastroenterology, Parc de Salut Mar University Hospital, BarcelonaR T Lawlor - ARC-Net Centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital trust of Verona, Verona, ItalyA Carrato - Department of Oncology, Ramón y Cajal Hospital, Madrid, and CIBERONC, SpainM Hidalgo - Clara Campal Integrated Oncological Centre, Sanchinarro Hospital, Madrid, SpainA Scarpa - ARC-Net Centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital trust of Verona, Verona, ItalyL Sharp - Institute of Health & Society, Newcastle University, UKL I Furlong - Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Pompeu Fabra Univeristy (UPF), Barcelona, SpainF X Real - Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, SpainC La Vecchia - Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro," Department of Clinical Sciences and Community Health, University of Milan, MilanN Malats - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, and CIBERONC, SpainPanGenEU Study InvestigatorsJ Huang - Karolinska Institutet
- Resource Type
- Journal article
- Publication Details
- Annals of oncology, Vol.28(7), pp.1618-1624
- Publisher
- England
- DOI
- 10.1093/annonc/mdx167
- PMID
- 28383714
- ISSN
- 1569-8041
- eISSN
- 1569-8041
- Grant note
- 15-0391 / Worldwide Cancer Research
- Language
- English
- Date published
- 07/01/2017
- Academic Unit
- Epidemiology; Pathology
- Record Identifier
- 9983995130002771
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