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A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma
M. Giaccherini, M. Rende, M. Gentiluomo, C. Corradi, L. Archibugi, S. Ermini, E. Maiello, L. Morelli, CHJ. van Eijck, GM. Cavestro, M. Schneider, A. Mickevicius, K. Adamonis, D. Basso, V. Hlavac, D. Gioffreda, R. Talar-Wojnarowska, B. Schöttker,...
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, metaanalýza
Grantová podpora
#PI061614
Instituto de Salud Carlos III
SU2C #6179
Lustgarten Foundation & Stand-Up to Cancer
Italian Ministry of Health
PubMed
38606763
DOI
10.1093/mutage/geae012
Knihovny.cz E-zdroje
- MeSH
- celogenomová asociační studie * MeSH
- duktální karcinom slinivky břišní * genetika MeSH
- genetická pleiotropie * MeSH
- genetická predispozice k nemoci * MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- lidské chromozomy, pár 10 genetika MeSH
- lidské chromozomy, pár 7 genetika MeSH
- nádory slinivky břišní * genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Pleiotropic variants (i.e. genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted 10 years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61 052 variants reported to be associated by at least one genome-wide association study with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16 055 pancreatic ductal adenocarcinoma (PDAC) cases and 212 149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P = 6.52 × 10-5) and 7q36.3-rs288762 (P = 3.03 × 10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell-differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.
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
Blood Transfusion Service Azienda Ospedaliero Universitaria Meyer Florence Italy
Carol Davila University of Medicine and Pharmacy Bucharest Romania
Center for Translational Medicine Semmelweis University Budapest Hungary
Center for Translational Research in Oncology São Paulo Brazil
Centre for Translational Medicine Department of Medicine University of Szeged Szeged Hungary
County Medical Association of Potenza Potenza Italy
Department of Biology University of Pisa Pisa Italy
Department of Biomedical Sciences Humanitas University Milan Italy
Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland
Department of Oncology Palacky University Olomouc Olomouc Czech Republic
Department of Surgery 1 University Hospital Olomouc Olomouc Czech Republic
Department of Surgery Erasmus MC University Medical Center Rotterdam The Netherlands
Department of Surgery Oncology and Gastroenterology DiSCOG University of Padova Padua Italy
Digestive and Liver Disease Unit Sant'Andrea Hospital Rome Italy
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of General and Transplant Surgery Pisa University Hospital Pisa Italy
Division of Pancreatic Diseases Heart and Vascular Center Semmelweis University Budapest Hungary
Division of Preventive Oncology German Cancer Research Center Heidelberg Germany
Fundeni Clinical Institute Bucharest Romania
Gastroenterology Department Lithuanian University of Health Sciences Kaunas Lithuania
Gastrointestinal Endoscopy Unit Vita Salute San Raffaele University IRCCS San Raffaele Milan Italy
Genetic and Molecular Epidemiology Group Spanish National Cancer Research Centre Madrid Spain
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
German Cancer Consortium Heidelberg Germany
Institute of Experimental Medicine Czech Academy of Science Prague Czech Republic
János Szentágothai Research Center University of Pécs Pécs Hungary
Medical Faculty Heidelberg Heidelberg University Heidelberg Germany
Medical School Institute for Translational Medicine University of Pécs Pécs Hungary
Network Aging Research Heidelberg University Heidelberg Germany
Oncode Institute Amsterdam The Netherlands
Oncological Department Massa Carrara Azienda USL Toscana Nord Ovest Carrara Italy
Pancreatic Unit Humanitas Clinical and Research Center IRCCS Milan Italy
Surgery Clinic 3rd Faculty of Medicine Charles University Prague Czech Republic
Surgery Department Lithuanian University of Health Sciences Kaunas Lithuania
Citace poskytuje Crossref.org
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- $a Pleiotropic variants (i.e. genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted 10 years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61 052 variants reported to be associated by at least one genome-wide association study with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16 055 pancreatic ductal adenocarcinoma (PDAC) cases and 212 149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P = 6.52 × 10-5) and 7q36.3-rs288762 (P = 3.03 × 10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell-differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.
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