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Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Duell EJ 1 , Lujan-Barroso L 1 , Sala N 1 , Deitz McElyea S 2 , Overvad K 3 , Tjonneland A 4 Show all authors , Olsen A 4 , Weiderpass E 5 , Busund LT 6 , Moi L 6 , Muller D 7 , Vineis P 7 , Aune D 7 , Matullo G 8 , Naccarati A 8 , Panico S 9 , Tagliabue G 10 , Tumino R 11 , Palli D 12 , Kaaks R 13 , Katzke VA 13 , Boeing H 14 , Bueno-de-Mesquita HBA 15 , Peeters PH 16 , Trichopoulou A 17 , Lagiou P 17 , Kotanidou A 17 , Travis RC 18 , Wareham N 19 , Khaw KT 19 , Ramon Quiros J 20 , Rodríguez-Barranco M 21 , Dorronsoro M 22 , Chirlaque MD 22 , Ardanaz E 22 , Severi G 23 , Boutron-Ruault MC 23 , Rebours V 24 , Brennan P 25 , Gunter M 25 , Scelo G 25 , Cote G 26 , Sherman S 2 , Korc M 27

Affiliations 

  • 1 Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
  • 2 Department of Medicine, Indiana University School of Medicine, Indianapolis, IN
  • 3 Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus C, Denmark
  • 4 Danish Cancer Society Research Center, Copenhagen, Denmark
  • 5 Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway
  • 6 Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway
  • 7 School of Public Health, Epidemiology & Biostatistics, Imperial College London, London, United Kingdom
  • 8 Human Genetics Foundation (HuGeF), Turin, Italy
  • 9 Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
  • 10 Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
  • 11 Cancer Registry and Histopathology Unit, "Civic - M.P, Arezzo" Hospital, ASP, Ragusa, Italy
  • 12 Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy
  • 13 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 14 Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany
  • 15 Dt. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
  • 16 Dept of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  • 17 Hellenic Health Foundation, Athens, Greece
  • 18 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
  • 19 MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom
  • 20 Public Health Directorate, Asturias, Spain
  • 21 Andalusian School of Public Health, Research Insititute Biosanitary Granada, University Hospital Granada/University of Granada, Granada
  • 22 CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
  • 23 Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France
  • 24 Beaujon Hospital, Pancreatology Unit, Clichy, France
  • 25 International Agency for Research on Cancer (IARC), Lyon, France
  • 26 Medical University of South Carolina, Charleston, SC
  • 27 Departments of Medicine and Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN
Int J Cancer, 2017 Sep 01;141(5):905-915.
PMID: 28542740 DOI: 10.1002/ijc.30790

Abstract

Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155 and -212) overall, and for four miRs (-10a, -10b, -21-5p and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (p-value = 0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-5p).

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