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 journalArticle

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

Fingerprint

Systems Analysis
Pancreatic Neoplasms
Comorbidity
Adenocarcinoma
Odds Ratio
Computational Biology
Type 2 Diabetes Mellitus
Stomach
Hypersensitivity
Logistic Models
Heartburn
Gastric Acid
Helicobacter Infections
Hypercholesterolemia
Principal Component Analysis
Early Detection of Cancer
Nose
Helicobacter pylori
Population
Statistical Factor Analysis

Keywords

  • multimorbidity
  • pancreatic cancer
  • risk

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

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

In: Annals of oncology : official journal of the European Society for Medical Oncology, Vol. 28, No. 7, 01.07.2017, p. 1618-1624.

Research output: Contribution to journalArticle

Gomez-Rubio, P, Rosato, V, Márquez, M, Bosetti, C, Molina-Montes, E, Rava, M, Piñero, J, Michalski, CW, Farré, A, Molero, X, Löhr, M, Ilzarbe, L, Perea, J, Greenhalf, W, O'Rorke, M, Tardón, A, Gress, T, Barberá, VM, Crnogorac-Jurcevic, T, Muñoz-Bellvís, L, Domínguez-Muñoz, E, Gutiérrez-Sacristán, A, Balsells, J, Costello, E, Guillén-Ponce, C, Huang, J, Iglesias, M, Kleeff, J, Kong, B, Mora, J, Murray, L, O'Driscoll, D, Peláez, P, Poves, I, Lawlor, RT, Carrato, A, Hidalgo, M, Scarpa, A, Sharp, L, Furlong, LI, Real, FX, La Vecchia, C, Malats, N & PanGenEU Study Investigators 2017, 'A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk', Annals of oncology : official journal of the European Society for Medical Oncology, vol. 28, no. 7, pp. 1618-1624. https://doi.org/10.1093/annonc/mdx167
Gomez-Rubio, P. ; Rosato, V. ; Márquez, M. ; Bosetti, C. ; Molina-Montes, E. ; Rava, M. ; Piñero, J. ; Michalski, C. W. ; Farré, A. ; Molero, X. ; Löhr, M. ; Ilzarbe, L. ; Perea, J. ; Greenhalf, W. ; O'Rorke, M. ; Tardón, A. ; Gress, T. ; Barberá, V. M. ; Crnogorac-Jurcevic, T. ; Muñoz-Bellvís, L. ; Domínguez-Muñoz, E. ; Gutiérrez-Sacristán, A. ; Balsells, J. ; Costello, E. ; Guillén-Ponce, C. ; Huang, J. ; Iglesias, M. ; Kleeff, J. ; Kong, B. ; Mora, J. ; Murray, L. ; O'Driscoll, D. ; Peláez, P. ; Poves, I. ; Lawlor, R. T. ; Carrato, A. ; Hidalgo, M. ; Scarpa, A. ; Sharp, L. ; Furlong, L. I. ; Real, F. X. ; La Vecchia, C. ; Malats, N. ; PanGenEU Study Investigators. / A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk. In: Annals of oncology : official journal of the European Society for Medical Oncology. 2017 ; Vol. 28, No. 7. pp. 1618-1624.
@article{0194c5370be04ec988df87f1f05d65b4,
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.",
keywords = "multimorbidity, pancreatic cancer, risk",
author = "P. Gomez-Rubio and V. Rosato and M. M{\'a}rquez and C. Bosetti and E. Molina-Montes and M. Rava and J. Pi{\~n}ero and Michalski, {C. W.} and A. Farr{\'e} and X. Molero and M. L{\"o}hr and L. Ilzarbe and J. Perea and W. Greenhalf and M. O'Rorke and A. Tard{\'o}n and T. Gress and Barber{\'a}, {V. M.} and T. Crnogorac-Jurcevic and L. Mu{\~n}oz-Bellv{\'i}s and E. Dom{\'i}nguez-Mu{\~n}oz and A. Guti{\'e}rrez-Sacrist{\'a}n and J. Balsells and E. Costello and C. Guill{\'e}n-Ponce and J. Huang and M. Iglesias and J. Kleeff and B. Kong and J. Mora and L. Murray and D. O'Driscoll and P. Pel{\'a}ez and I. Poves and Lawlor, {R. T.} and A. Carrato and M. Hidalgo and A. Scarpa and L. Sharp and Furlong, {L. I.} and Real, {F. X.} and {La Vecchia}, C. and N. Malats and {PanGenEU Study Investigators}",
year = "2017",
month = "7",
day = "1",
doi = "10.1093/annonc/mdx167",
language = "English",
volume = "28",
pages = "1618--1624",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "7",

}

TY - JOUR

T1 - A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk

AU - Gomez-Rubio, P.

AU - Rosato, V.

AU - Márquez, M.

AU - Bosetti, C.

AU - Molina-Montes, E.

AU - Rava, M.

AU - Piñero, J.

AU - Michalski, C. W.

AU - Farré, A.

AU - Molero, X.

AU - Löhr, M.

AU - Ilzarbe, L.

AU - Perea, J.

AU - Greenhalf, W.

AU - O'Rorke, M.

AU - Tardón, A.

AU - Gress, T.

AU - Barberá, V. M.

AU - Crnogorac-Jurcevic, T.

AU - Muñoz-Bellvís, L.

AU - Domínguez-Muñoz, E.

AU - Gutiérrez-Sacristán, A.

AU - Balsells, J.

AU - Costello, E.

AU - Guillén-Ponce, C.

AU - Huang, J.

AU - Iglesias, M.

AU - Kleeff, J.

AU - Kong, B.

AU - Mora, J.

AU - Murray, L.

AU - O'Driscoll, D.

AU - Peláez, P.

AU - Poves, I.

AU - Lawlor, R. T.

AU - Carrato, A.

AU - Hidalgo, M.

AU - Scarpa, A.

AU - Sharp, L.

AU - Furlong, L. I.

AU - Real, F. X.

AU - La Vecchia, C.

AU - Malats, N.

AU - PanGenEU Study Investigators

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - multimorbidity

KW - pancreatic cancer

KW - risk

UR - http://www.scopus.com/inward/record.url?scp=85029187330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029187330&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdx167

DO - 10.1093/annonc/mdx167

M3 - Article

C2 - 28383714

AN - SCOPUS:85029187330

VL - 28

SP - 1618

EP - 1624

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 7

ER -