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

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Title: Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study
Authors: Duell, EJ
Lujan-Barroso, L
Sala, N
McElyea, SD
Overvad, K
Tjonneland, A
Olsen, A
Weiderpass, E
Busund, L-T
Moi, L
Muller, D
Vineis, P
Aune, D
Matullo, G
Naccarati, A
Panico, S
Tagliabue, G
Tumino, R
Palli, D
Kaaks, R
Katzke, VA
Boeing, H
Bueno-de-Mesquita, HBA
Peeters, PH
Trichopoulou, A
Lagiou, P
Kotanidou, A
Travis, RC
Wareham, N
Khaw, K-T
Quiros, JR
Rodriguez-Barranco, M
Dorronsoro, M
Chirlaque, M-D
Ardanaz, E
Severi, G
Boutron-Ruault, M-C
Rebours, V
Brennan, P
Gunter, M
Scelo, G
Cote, G
Sherman, S
Korc, M
Item Type: Journal Article
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).
Issue Date: 12-Jun-2017
Date of Acceptance: 19-Apr-2017
URI: http://hdl.handle.net/10044/1/52747
DOI: https://dx.doi.org/10.1002/ijc.30790
ISSN: 0020-7136
Publisher: Wiley
Start Page: 905
End Page: 915
Journal / Book Title: International Journal of Cancer
Volume: 141
Issue: 5
Copyright Statement: © 2017 UICC. This is the pre-peer reviewed version of the following article, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/ijc.30790/abstract
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
biomarkers
microRNAs
pancreatic cancer
cohort studies
DUCTAL ADENOCARCINOMA
POOR-PROGNOSIS
EXPRESSION
DIAGNOSIS
PROMOTES
SURVIVAL
CELLS
MICROENVIRONMENT
EVOLUTION
PATTERNS
Adult
Aged
Area Under Curve
Biomarkers, Tumor
Carcinoma, Pancreatic Ductal
Case-Control Studies
Female
Humans
Male
MicroRNAs
Middle Aged
Pancreatic Neoplasms
Polymerase Chain Reaction
Prospective Studies
ROC Curve
Sensitivity and Specificity
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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