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Publications

Journal Article Ahead of print

PubMed: 42334072 DOI: 10.1002/ijc.70581

Immune Markers and Risk of Pancreatic Cancer in the European EPIC Cohort.

Int J Cancer

Authors: Verena A Katzke, Yue Chen, Srimanti Dutta, Federico Canzian, Julie Louise Munk Andersen, Agnetha Linn Rostgaard-Hansen, Léa Bouteille, Vinciane Rebours, Thérèse Truong, Matthias B Schulze, Benedetta Bendinelli, Valeria Pala, Vittorio Simeon, Rosario Tumino, Carlotta Sacerdote, Roel Vermeulen, P Martijn Kolijn, Sjoerd G Elias, Marta Crous-Bou, Maria-José Sánchez, Ana Jimenez-Zabala, José María Huerta, Marcela Guevara, Nick Wareham, Marie Breeur, Mattias Johansson, James Yarmolinsky, Daniele Campa, Rudolf Kaaks

Affiliations

  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • The Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Ludwig Maximilian University of Munich, Munich, Germany.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Danish Cancer Institute, Copenhagen, Denmark.
  • Department of Public Health, Aarhus University, Aarhus, Denmark.
  • Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France.
  • Department of Pancreatology and Digestive Oncology, Beaujon Hospital, AP-HP, Paris-Cité University, Clichy, France.
  • Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
  • Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
  • Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-ISPRO, Florence, Italy.
  • Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, Milan, Italy.
  • Medical Statistics Unit, University "L. Vanvitelli", Naples, Italy.
  • Hyblean Association for Epidemiology Research, A.I.R.Ep. ETS, Ragusa, Italy.
  • Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
  • Division of Environmental Epidemiology and Veterinary Public Health, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
  • Julius Global Health, the Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.
  • Department of Epidemiology and Health Economics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Escuela Andaluza de Salud Pública (EASP), Granada, Spain.
  • Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.
  • Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
  • Biogipuzkoa Health Research Institute, Group of Epidemiology of Chronic and Communicable Diseases, San Sebastian, Gipuzkoa, Spain.
  • Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Gipuzkoa, Spain.
  • Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain.
  • Research Group on Epidemiology and Public Health, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), Murcia, Spain.
  • Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain.
  • Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
  • MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
  • Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Early Detection, Prevention, and Infections Branch (EPR), International Agency for Research on Cancer (IARC/WHO), Lyon, France.
  • Imperial College London, London, UK.
  • Department of Biology, University of Pisa, Pisa, Italy.

Abstract

The immune system is a major driver in pancreatic cancer development. Several prospective cohort studies have found associations for single immune system-derived proteins such as IL6 or CRP, but results are inconclusive, and Omics-based research is scarce. Hence, we aimed to investigate associations of a comprehensive protein panel with the risk of pancreatic cancer. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 92 immune proteins were measured in baseline blood samples of 406 incident pancreatic cancer cases and 406 sex- and age-matched controls, using the Olink Immuno-Oncology panel. Multivariable adjusted conditional logistic regression was used to estimate odds ratios (OR, 95% CI) for protein levels in association with pancreatic cancer risk. Eight biomarkers were associated with pancreatic cancer risk (MMP12, LAMP3, CD28, IL-6, IL-12, FASLG, PD-L2, and PDCD1) but only MMP12 was significantly associated after multivariable adjustments for confounders and the seven proteins, with OR = 1.56 (95% CI: 1.20-2.03) for a doubling in protein concentration. After correction for multiple testing, none of the proteins were associated with risk. Restricting analyses to cases diagnosed within the first 4 years and 4-8 years after recruitment resulted in OR of 1.89 (95% CI: 1.28-2.80) and 1.37 (95% CI: 1.01-1.86) for MMP12, respectively. Higher levels of MMP12 were associated with pancreatic cancer risk specifically in those diagnosed shortly after recruitment, while other immune-related factors were not associated with risk. Further cohort studies are needed to confirm our initial findings.

MeSH

Pancreatic Neoplasms, Neoplasms, Interleukin-6, Cohort Studies, Immune System