Association of genetic variants affecting microRNAs and pancreatic cancer risk

Lu, Y.; Corradi, C.; Gentiluomo, M.; Theodoropoulos, G.; Roth, S.; Maiello, E.; Morelli, L.; Archibugi, L.; Izbicki, J. R.; Sarlos, P.; Kiudelis, V.; Oliverius, M.; Nobrega Aoki, M.; Vashist, Y.; van Eijck, C. H. J.; Gazouli, M.; Talar-Wojnarowska, R.; Mambrini, A.; Pezzilli, R.; Bueno-de-Mesquita, B.; Hegyi, P.; Soucek, P.; Neoptolemos, J. P.; Di Franco, G.; Sperti, C.; Kauffmann, E. F.; Uzunoglu, F. G.; Ermini, S.; Małecka-Panas, E.; Lucchesi, M.; Vanella, G.; Djik, F.; Mohelnikova-Duchonova, B.; Bambi, F.; Petrone, M. C.; Jamroziak, K.; Guo, F.; Kolarova, K.; Capretti, G.; Milanetto, A. C.; Ginocchi, L.; Lovecek, M.; Puzzono, M.; van Laarhoven, H. W. M.; Carrara, S.; Ivanauskas, A.; Papiris, K.; Basso, D.; Arcidiacono, P.; Izbeki, F.; Chammas, R.; Vodicka, P.; Hackert, T.; Pasquali, C.; Piredda, M. L.; Costello-Goldring, E.; Cavestro, G. M.; Szentesi, A.; Tavano, F; Wlodarczyk, B.; Brenner, H.; Kreivenaite, E.; Gao, X.; Bunduc, S.; Vermeulen, R. C. H.; Schneider, M. A.; Laitiano, A.; Gioffreda, D.; Testoni, S. G. G.; Kupcinskas, J.; Lawlor, R.; Capurso, G.; Malats, N.; Campa, D.; Canzian, F.

doi:10.3389/fgene.2021.693933

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 popul...