Journal Article

DKFZ-2021-02176

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk.

Lu, Y. (First author)DKFZ* ; Corradi, C. ; Gentiluomo, M. ; López de Maturana, E. ; Theodoropoulos, G. E. ; Roth, S. ; Maiello, E. ; Morelli, L. ; Archibugi, L. ; Izbicki, J. R. ; Sarlós, P. ; Kiudelis, V. ; Oliverius, M. ; Aoki, M. N. ; Vashist, Y. ; van Eijck, C. H. J. ; Gazouli, M. ; Talar-Wojnarowska, R. ; Mambrini, A. ; Pezzilli, R. ; Bueno-de-Mesquita, B. ; Hegyi, P. ; Souček, P. ; Neoptolemos, J. P. ; Di Franco, G. ; Sperti, C. ; Kauffmann, E. F. ; Hlaváč, V. ; Uzunoğlu, F. G. ; Ermini, S. ; Małecka-Panas, E. ; Lucchesi, M. ; Vanella, G. ; Dijk, F. ; Mohelníková-Duchoňová, B. ; Bambi, F. ; Petrone, M. C. ; Jamroziak, K. ; Guo, F.DKFZ* ; Kolarova, K. ; Capretti, G. ; Milanetto, A. C. ; Ginocchi, L. ; Loveček, M. ; Puzzono, M. ; van Laarhoven, H. W. M. ; Carrara, S. ; Ivanauskas, A. ; Papiris, K. ; Basso, D. ; Arcidiacono, P. G. ; Izbéki, F. ; Chammas, R. ; Vodicka, P. ; Hackert, T. ; Pasquali, C. ; Piredda, M. L. ; Costello-Goldring, E. ; Cavestro, G. M. ; Szentesi, A. ; Tavano, F. ; Włodarczyk, B. ; Brenner, H.DKFZ* ; Kreivenaite, E. ; Gao, X.DKFZ* ; Bunduc, S. ; Vermeulen, R. C. H. ; Schneider, M. A. ; Latiano, A. ; Gioffreda, D. ; Testoni, S. G. G. ; Kupcinskas, J. ; Lawlor, R. T. ; Capurso, G. ; Malats, N. ; Campa, D. ; Canzian, F. (Last author)DKFZ*

2021
Frontiers Media Lausanne

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Please use a persistent id in citations: doi:10.3389/fgene.2021.693933

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 × 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.

Keyword(s): genetic polymorphisms ; miRNA ; pancreatic cancer ; pancreatic ductal adenocarcinoma ; susceptibility

Note: #EA:C055#LA:C055#

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Contributing Institute(s):

1. C055 Genomische Epidemiologie (C055)
2. C070 Klinische Epidemiologie und Alternf. (C070)
3. Präventive Onkologie (C120)
4. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2021

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