Περίληψη:
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.
Συγγραφείς:
Lu, Ye
Corradi, Chiara
Gentiluomo, Manuel
Lopez de Maturana,
Evangelina
Theodoropoulos, George E.
Roth, Susanne
Maiello,
Evaristo
Morelli, Luca
Archibugi, Livia
Izbicki, Jakob R.
and Sarlos, Patricia
Kiudelis, Vytautas
Oliverius, Martin and
Aoki, Mateus Nobrega
Vashist, Yogesh
van Eijck, Casper H. J. and
Gazouli, Maria
Talar-Wojnarowska, Renata
Mambrini, Andrea and
Pezzilli, Raffaele
Bueno-de-Mesquita, Bas
Hegyi, Peter and
Soucek, Pavel
Neoptolemos, John P.
Di Franco, Gregorio and
Sperti, Cosimo
Kauffmann, Emanuele F.
Hlavac, Viktor and
Uzunoglu, Faik G.
Ermini, Stefano
Malecka-Panas, Ewa and
Lucchesi, Maurizio
Vanella, Giuseppe
Dijk, Frederike and
Mohelnikova-Duchonova, Beatrice
Bambi, Franco
Petrone, Maria
Chiara
Jamroziak, Krzysztof
Guo, Feng
Kolarova, Katerina and
Capretti, Giovanni
Milanetto, Anna Caterina
Ginocchi, Laura and
Lovecek, Martin
Puzzono, Marta
van Laarhoven, Hanneke W. M. and
Carrara, Silvia
Ivanauskas, Audrius
Papiris, Konstantinos and
Basso, Daniela
Arcidiacono, Paolo G.
Izbeki, Ferenc
Chammas,
Roger
Vodicka, Pavel
Hackert, Thilo
Pasquali, Claudio and
Piredda, Maria L.
Costello-Goldring, Eithne
Cavestro, Giulia
Martina
Szentesi, Andrea
Tavano, Francesca
Wlodarczyk,
Barbara
Brenner, Hermann
Kreivenaite, Edita
Gao, Xin and
Bunduc, Stefania
Vermeulen, Roel C. H.
Schneider, Martin A. and
Latiano, Anna
Gioffreda, Domenica
Testoni, Sabrina G. G. and
Kupcinskas, Juozas
Lawlor, Rita T.
Capurso, Gabriele
Malats,
Nuria
Campa, Daniele
Canzian, Federico
