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Lu, Ye; Corradi, Chiara; Gentiluomo, Manuel; López de Maturana, Evangelina; Theodoropoulos, George E.; Roth, Susanne; Maiello, Evaristo; Morelli, Luca; Archibugi, Livia; Izbicki, Jakob R.; Sarlós, Patricia; Kiudelis, Vytautas; Oliverius, Martin; Aoki, Mateus Nóbrega; Vashist, Yogesh; van Eijck, Casper H. J.; Gazouli, Maria; Talar-Wojnarowska, Renata; Mambrini, Andrea; Pezzilli, Raffaele; Bueno-de-Mesquita, Bas; Hegyi, Péter; Souček, Pavel; Neoptolemos, John P.; [...]

Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk

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  • Medientyp: E-Artikel
  • Titel: Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk
  • Beteiligte: Lu, Ye; Corradi, Chiara; Gentiluomo, Manuel; López de Maturana, Evangelina; Theodoropoulos, George E.; Roth, Susanne; Maiello, Evaristo; Morelli, Luca; Archibugi, Livia; Izbicki, Jakob R.; Sarlós, Patricia; Kiudelis, Vytautas; Oliverius, Martin; Aoki, Mateus Nóbrega; Vashist, Yogesh; van Eijck, Casper H. J.; Gazouli, Maria; Talar-Wojnarowska, Renata; Mambrini, Andrea; Pezzilli, Raffaele; Bueno-de-Mesquita, Bas; Hegyi, Péter; Souček, Pavel; Neoptolemos, John P.; [...]
  • Erschienen: Frontiers Media SA, 2021
  • Erschienen in: Frontiers in Genetics, 12 (2021)
  • Sprache: Nicht zu entscheiden
  • DOI: 10.3389/fgene.2021.693933
  • ISSN: 1664-8021
  • Schlagwörter: Genetics (clinical) ; Genetics ; Molecular Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>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 <jats:italic>in silico</jats:italic> 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 <jats:italic>p</jats:italic> 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, <jats:italic>p</jats:italic> = 3.03 × 10<jats:sup>−6</jats:sup> in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of <jats:italic>UCHL3</jats:italic>, 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.</jats:p>
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