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| 001 | 176936 | ||
| 005 | 20240229133725.0 | ||
| 024 | 7 | _ | |a 10.3389/fgene.2021.693933 |2 doi |
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| 100 | 1 | _ | |a Lu, Ye |0 P:(DE-He78)ebb819874e9553d89bd480e6811dc0f3 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk. |
| 260 | _ | _ | |a Lausanne |c 2021 |b Frontiers Media |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1634036444_10607 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 520 | _ | _ | |a 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 × 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. |
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| 650 | _ | 7 | |a genetic polymorphisms |2 Other |
| 650 | _ | 7 | |a miRNA |2 Other |
| 650 | _ | 7 | |a pancreatic cancer |2 Other |
| 650 | _ | 7 | |a pancreatic ductal adenocarcinoma |2 Other |
| 650 | _ | 7 | |a susceptibility |2 Other |
| 700 | 1 | _ | |a Corradi, Chiara |b 1 |
| 700 | 1 | _ | |a Gentiluomo, Manuel |b 2 |
| 700 | 1 | _ | |a López de Maturana, Evangelina |b 3 |
| 700 | 1 | _ | |a Theodoropoulos, George E |b 4 |
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| 700 | 1 | _ | |a Vashist, Yogesh |b 14 |
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| 773 | _ | _ | |a 10.3389/fgene.2021.693933 |g Vol. 12, p. 693933 |0 PERI:(DE-600)2606823-0 |p 693933 |t Frontiers in genetics |v 12 |y 2021 |x 1664-8021 |
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