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Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility
C. Corradi, M. Gentiluomo, L. Gajdán, GM. Cavestro, E. Kreivenaite, G. Di Franco, C. Sperti, M. Giaccherini, MC. Petrone, F. Tavano, D. Gioffreda, L. Morelli, P. Soucek, A. Andriulli, JR. Izbicki, N. Napoli, E. Małecka-Panas, P. Hegyi, JP....
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
33534179
DOI
10.1002/ijc.33475
Knihovny.cz E-resources
- MeSH
- Genome-Wide Association Study MeSH
- Carcinoma, Pancreatic Ductal genetics MeSH
- Genetic Predisposition to Disease MeSH
- Cyclin-Dependent Kinase Inhibitor p15 genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Pancreatic Neoplasms genetics MeSH
- RNA, Long Noncoding genetics MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Computational Biology methods MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10-9 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.
1st Department of Medicine University of Szeged Szeged Hungary
ARC NET Centre for Applied Research on Cancer University and Hospital Trust of Verona Verona Italy
Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Center of Gastroenterology Fundeni Clinical Institute Bucharest Romania
Department of Biology University of Pisa Pisa Italy
Department of Diagnostics and Public Health Section of pathology University of Verona Verona Italy
Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland
Department of Gastroenterology IRCCS Humanitas Research Hospital Endoscopic Unit Milan Italy
Department of General Surgery University of Heidelberg Heidelberg Germany
Department of Hematology Institute of Hematology and Transfusion Medicine Warsaw Poland
Department of Surgery Oncology and Gastroenterology DiSCOG University of Padova Padova Italy
Division of Preventive Oncology German Cancer Research Center Heidelberg Germany
Gastroenterology San Carlo Hospital Potenza Italy
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
German Cancer Consortium Heidelberg Germany
Institute for Translational Medicine Medical School University of Pécs Pécs Hungary
Institute of Biology and Medical Genetics 1st Medical Faculty Prague Czech Republic
Institute of Experimental Medicine Czech Academy of Sciences Prague Czech Republic
Sant'Andrea Hospital Faculty of Medicine and Psychology Sapienza University of Rome Rome Italy
Szent György University Teaching Hospital of Fejér County Székesfehérvár Hungary
UO Chirurgia Generale e dei Trapianti Università di Pisa Pisa Italy
References provided by Crossref.org
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- $a Corradi, Chiara $u Department of Biology, University of Pisa, Pisa, Italy
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