@article{3030957, title = "Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk", author = "Lu, Ye and Corradi, Chiara and Gentiluomo, Manuel and Lopez de Maturana, and Evangelina and Theodoropoulos, George E. and Roth, Susanne and Maiello, and Evaristo and Morelli, Luca and Archibugi, Livia and Izbicki, Jakob R. and and Sarlos, Patricia and Kiudelis, Vytautas and Oliverius, Martin and and Aoki, Mateus Nobrega and Vashist, Yogesh and van Eijck, Casper H. J. and and Gazouli, Maria and Talar-Wojnarowska, Renata and Mambrini, Andrea and and Pezzilli, Raffaele and Bueno-de-Mesquita, Bas and Hegyi, Peter and and Soucek, Pavel and Neoptolemos, John P. and Di Franco, Gregorio and and Sperti, Cosimo and Kauffmann, Emanuele F. and Hlavac, Viktor and and Uzunoglu, Faik G. and Ermini, Stefano and Malecka-Panas, Ewa and and Lucchesi, Maurizio and Vanella, Giuseppe and Dijk, Frederike and and Mohelnikova-Duchonova, Beatrice and Bambi, Franco and Petrone, Maria and Chiara and Jamroziak, Krzysztof and Guo, Feng and Kolarova, Katerina and and Capretti, Giovanni and Milanetto, Anna Caterina and Ginocchi, Laura and and Lovecek, Martin and Puzzono, Marta and van Laarhoven, Hanneke W. M. and and Carrara, Silvia and Ivanauskas, Audrius and Papiris, Konstantinos and and Basso, Daniela and Arcidiacono, Paolo G. and Izbeki, Ferenc and Chammas, and Roger and Vodicka, Pavel and Hackert, Thilo and Pasquali, Claudio and and Piredda, Maria L. and Costello-Goldring, Eithne and Cavestro, Giulia and Martina and Szentesi, Andrea and Tavano, Francesca and Wlodarczyk, and Barbara and Brenner, Hermann and Kreivenaite, Edita and Gao, Xin and and Bunduc, Stefania and Vermeulen, Roel C. H. and Schneider, Martin A. and and Latiano, Anna and Gioffreda, Domenica and Testoni, Sabrina G. G. and and Kupcinskas, Juozas and Lawlor, Rita T. and Capurso, Gabriele and Malats, and Nuria and Campa, Daniele and Canzian, Federico", journal = "FRONTIERS IN GENETICS", year = "2021", volume = "12", publisher = "Frontiers Media SA", doi = "10.3389/fgene.2021.693933", keywords = "pancreatic cancer; miRNA; genetic polymorphisms; susceptibility; pancreatic ductal adenocarcinoma", abstract = "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." }