TY - JOUR
TI - Association of Genetic Variants Affecting microRNAs and Pancreatic
Cancer Risk
AU - Lu, Ye
AU - Corradi, Chiara
AU - Gentiluomo, Manuel
AU - Lopez de Maturana,
AU - Evangelina
AU - Theodoropoulos, George E.
AU - Roth, Susanne
AU - Maiello,
AU - Evaristo
AU - Morelli, Luca
AU - Archibugi, Livia
AU - Izbicki, Jakob R.
AU - and Sarlos, Patricia
AU - Kiudelis, Vytautas
AU - Oliverius, Martin and
AU - Aoki, Mateus Nobrega
AU - Vashist, Yogesh
AU - van Eijck, Casper H. J. and
AU - Gazouli, Maria
AU - Talar-Wojnarowska, Renata
AU - Mambrini, Andrea and
AU - Pezzilli, Raffaele
AU - Bueno-de-Mesquita, Bas
AU - Hegyi, Peter and
AU - Soucek, Pavel
AU - Neoptolemos, John P.
AU - Di Franco, Gregorio and
AU - Sperti, Cosimo
AU - Kauffmann, Emanuele F.
AU - Hlavac, Viktor and
AU - Uzunoglu, Faik G.
AU - Ermini, Stefano
AU - Malecka-Panas, Ewa and
AU - Lucchesi, Maurizio
AU - Vanella, Giuseppe
AU - Dijk, Frederike and
AU - Mohelnikova-Duchonova, Beatrice
AU - Bambi, Franco
AU - Petrone, Maria
AU - Chiara
AU - Jamroziak, Krzysztof
AU - Guo, Feng
AU - Kolarova, Katerina and
AU - Capretti, Giovanni
AU - Milanetto, Anna Caterina
AU - Ginocchi, Laura and
AU - Lovecek, Martin
AU - Puzzono, Marta
AU - van Laarhoven, Hanneke W. M. and
AU - Carrara, Silvia
AU - Ivanauskas, Audrius
AU - Papiris, Konstantinos and
AU - Basso, Daniela
AU - Arcidiacono, Paolo G.
AU - Izbeki, Ferenc
AU - Chammas,
AU - Roger
AU - Vodicka, Pavel
AU - Hackert, Thilo
AU - Pasquali, Claudio and
AU - Piredda, Maria L.
AU - Costello-Goldring, Eithne
AU - Cavestro, Giulia
AU - Martina
AU - Szentesi, Andrea
AU - Tavano, Francesca
AU - Wlodarczyk,
AU - Barbara
AU - Brenner, Hermann
AU - Kreivenaite, Edita
AU - Gao, Xin and
AU - Bunduc, Stefania
AU - Vermeulen, Roel C. H.
AU - Schneider, Martin A. and
AU - Latiano, Anna
AU - Gioffreda, Domenica
AU - Testoni, Sabrina G. G. and
AU - Kupcinskas, Juozas
AU - Lawlor, Rita T.
AU - Capurso, Gabriele
AU - Malats,
AU - Nuria
AU - Campa, Daniele
AU - Canzian, Federico
JO - FRONTIERS IN GENETICS
PY - 2021
VL - 12
TODO - null
SP - null
PB - Frontiers Media SA
SN - null
TODO - 10.3389/fgene.2021.693933
TODO - pancreatic cancer; miRNA; genetic polymorphisms; susceptibility;
pancreatic ductal adenocarcinoma
TODO - Genetic factors play an important role in the susceptibility to
pancreatic cancer (PC). However, established loci explain a small
proportion of genetic heritability for PC; therefore, more progress is
needed to find the missing ones. We aimed at identifying single
nucleotide polymorphisms (SNPs) affecting PC risk through effects on
micro-RNA (miRNA) function. We searched in silico the genome for SNPs in
miRNA seed sequences or 3 prime untranslated regions (3’UTRs) of miRNA
target genes. Genome-wide association data of PC cases and controls from
the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic
Cancer Case-Control (PanC4) Consortium were re-analyzed for discovery,
and genotyping data from two additional consortia (PanGenEU and PANDoRA)
were used for replication, for a total of 14,062 cases and 11,261
controls. None of the SNPs reached genome-wide significance in the
meta-analysis, but for three of them the associations were in the same
direction in all the study populations and showed lower value of p in
the meta-analyses than in the discovery phase. Specifically, rs7985480
was consistently associated with PC risk (OR = 1.12, 95% CI 1.07-1.17,
p = 3.03 x 10(-6) in the meta-analysis). This SNP is in linkage
disequilibrium (LD) with rs2274048, which modulates binding of various
miRNAs to the 3’UTR of UCHL3, a gene involved in PC progression. In
conclusion, our results expand the knowledge of the genetic PC risk
through miRNA-related SNPs and show the usefulness of functional
prioritization to identify genetic polymorphisms associated with PC
risk.
ER -