Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk
Jazyk angličtina Země Anglie, Velká Británie Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
29017
Cancer Research UK - United Kingdom
LX22NPO5102
National Institute for Cancer Research - NICR (Programme EXCELES)
PubMed
38308339
PubMed Central
PMC10837899
DOI
10.1186/s40246-024-00576-x
PII: 10.1186/s40246-024-00576-x
Knihovny.cz E-zdroje
- Klíčová slova
- Association study, Enhancer, Pancreatic cancer, Single nucleotide polymorphism, Transcription factor binding site,
- MeSH
- celogenomová asociační studie MeSH
- duktální karcinom slinivky břišní * genetika patologie MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- nádory slinivky břišní * genetika epidemiologie patologie MeSH
- regulační oblasti nukleových kyselin MeSH
- transkripční faktory genetika metabolismus MeSH
- vazebná místa genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- transkripční faktory MeSH
Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.
Biomedical Center Faculty of Medicine in Pilsen Charles University Plzeň Czech Republic
Blood Transfusion Service Meyer Children's Hospital Florence Italy
Cancer Center Amsterdam Imaging and Biomarkers Amsterdam the Netherlands
Carol Davila University of Medicine and Pharmacy Bucharest Romania
Center for Translational Medicine Semmelweis University Budapest Hungary
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 Gastroenterology San Carlo Hospital Potenza Italy
Department of Medicine Laboratory Medicine University of Padova Padua Italy
Department of Oncology Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic
Department of Radiology and Oncology Institute of Cancer of São Paulo São Paulo Brazil
Department of Surgery Erasmus MC University Medical Center Rotterdam The Netherlands
Department of Surgery Oncology and Gastroenterology University of Padova Padua Italy
Digestive and Liver Disease Unit S Andrea Hospital Rome Italy
Division of General and Transplant Surgery Pisa University Hospital Pisa Italy
Division of Pancreatic Diseases Heart and Vascular Center Semmelweis University Budapest Hungary
Endoscopic Unit Department of Gastroenterology IRCCS Humanitas Research Hospital Milan Italy
German Cancer Consortium German Cancer Research Center Heidelberg Germany
Institute for Translational Medicine Medical School University of Pécs Pécs Hungary
János Szentágothai Research Center University of Pécs Pécs Hungary
Laboratory for Applied Science and Technology in Health Carlos Chagas Institute Curitiba PR Brazil
Laboratory of Biology Medical School National and Kapodistrian University of Athens Athens Greece
Network Aging Research Heidelberg University Heidelberg Germany
Pancreatic Unit IRCCS Humanitas Research Hospital Milan Italy
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