| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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