Format

Send to

Choose Destination
Int J Cancer. 2017 Sep 1;141(5):905-915. doi: 10.1002/ijc.30790. Epub 2017 Jun 12.

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

Author information

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 Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
7
Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
8
Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
9
Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
10
Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
11
School of Public Health, Epidemiology & Biostatistics, Imperial College London, London, United Kingdom.
12
Human Genetics Foundation (HuGeF), Turin, Italy.
13
Department of Medical Sciences, University of Turin, Turin, Italy.
14
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
15
Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
16
Cancer Registry and Histopathology Unit, "Civic - M.P, Arezzo" Hospital, ASP, Ragusa, Italy.
17
Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
18
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
19
Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany.
20
Dt. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
21
Dt. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
22
Dt. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
23
Dept of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
24
MRC-PHE Centre for Environment and Health, Dept of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
25
Hellenic Health Foundation, Athens, Greece.
26
WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece.
27
Department of Epidemiology, Harvard School of Public Health, Boston, MA.
28
Department of Critical Care Medicine & Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece.
29
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
30
MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
31
Public Health Directorate, Asturias, Spain.
32
Andalusian School of Public Health, Research Insititute Biosanitary Granada, University Hospital Granada/University of Granada, Granada.
33
CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.
34
Basque Regional Health Department, San Sebatian, Spain.
35
Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
36
Navarra Public Health Institute, Pamplona, Spain.
37
IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
38
Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.
39
Gustave Roussy, Villejuif, France.
40
Beaujon Hospital, Pancreatology Unit, Clichy, France.
41
INSERM, University Paris, France.
42
International Agency for Research on Cancer (IARC), Lyon, France.
43
Medical University of South Carolina, Charleston, SC.
44
Departments of Medicine and Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN.
45
Pancreatic Cancer Signature Center, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN.

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).

KEYWORDS:

biomarkers; cohort studies; microRNAs; pancreatic cancer

PMID:
28542740
PMCID:
PMC5536971
DOI:
10.1002/ijc.30790
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center