TY - JOUR
T1 - Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study
AU - Duell, Eric J.
AU - Lujan-Barroso, Leila
AU - Sala, Núria
AU - Deitz McElyea, Samantha
AU - Overvad, Kim
AU - Tjonneland, Anne
AU - Olsen, Anja
AU - Weiderpass, Elisabete
AU - Busund, Lill Tove
AU - Moi, Line
AU - Muller, David C.
AU - Vineis, Paolo
AU - Aune, Dagfinn
AU - Matullo, Giuseppe
AU - Naccarati, Alessio
AU - Panico, Salvatore
AU - Tagliabue, Giovanna
AU - Tumino, Rosario
AU - Palli, Domenico
AU - Kaaks, Rudolf
AU - Katzke, Verena A.
AU - Boeing, Heiner
AU - Bueno-de-Mesquita, H. Bas
AU - Peeters, Petra H.
AU - Trichopoulou, Antonia
AU - Lagiou, Pagona
AU - Kotanidou, Anastasia
AU - Travis, Ruth C.
AU - Wareham, Nick
AU - Khaw, Kay Tee
AU - Ramon Quiros, Jose
AU - Rodríguez-Barranco, Miguel
AU - Dorronsoro, Miren
AU - Chirlaque, María Dolores
AU - Ardanaz, Eva
AU - Severi, Gianluca
AU - Boutron-Ruault, Marie Christine
AU - Rebours, Vinciane
AU - Brennan, Paul
AU - Gunter, Marc J.
AU - Scelo, Ghislaine
AU - Cote, Greg
AU - Sherman, Stuart
AU - Korc, Murray
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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).
AB - 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).
KW - biomarkers
KW - cohort studies
KW - microRNAs
KW - pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=85020392010&partnerID=8YFLogxK
U2 - 10.1002/ijc.30790
DO - 10.1002/ijc.30790
M3 - Article
C2 - 28542740
AN - SCOPUS:85020392010
SN - 0020-7136
VL - 141
SP - 905
EP - 915
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 5
ER -