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Autor
Albanes, Demetrius 1 Amundadottir, Laufey T 1 Andreotti, Gabriella 1 Arslan, Alan A 1 Babic, Ana 1 Bamlet, William R 1 Beane-Freeman, Laura 1 Berndt, Sonja I 1 Borgida, Ayelet 1 Boutron-Ruault, Marie-Christine 1 Bracci, Paige M 1 Brais, Lauren 1 Brennan, Paul 1 Bueno-de-Mesquita, Bas 1 Buring, Julie 1 Canzian, Federico 1 Chaffee, Kari G 1 Chanock, Stephen 1 Childs, Erica J 1 Cleary, Sean 1
- Organizace
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Pracoviště
CIBER Epidemiología y Salud Pública U... 1 CIBERONC Madrid Spain Epithelial Carc... 1 Cancer Care Ontario University of Tor... 1 Cancer Epidemiology Program Universit... 1 Cancer Epidemiology and Intelligence ... 1 Cancer Epidemiology and Intelligence ... 1 Cancer Epidemiology and Intelligence ... 1 Centre de Recherche en Épidémiologie ... 1 Department for Determinants of Chroni... 1 Department of Cancer Epidemiology and... 1 Department of Chronic Disease Epidemi... 1 Department of Epidemiology Harvard T ... 1 Department of Epidemiology Johns Hopk... 1 Department of Epidemiology University... 1 Department of Epidemiology and Biosta... 1 Department of Epidemiology and Biosta... 1 Department of Epidemiology and Enviro... 1 Department of Epidemiology and Public... 1 Department of Gastrointestinal Medica... 1 Department of General Surgery Univers... 1
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Autor
Albanes, Demetrius 1 Amundadottir, Laufey T 1 Andreotti, Gabriella 1 Arslan, Alan A 1 Babic, Ana 1 Bamlet, William R 1 Beane-Freeman, Laura 1 Berndt, Sonja I 1 Borgida, Ayelet 1 Boutron-Ruault, Marie-Christine 1 Bracci, Paige M 1 Brais, Lauren 1 Brennan, Paul 1 Bueno-de-Mesquita, Bas 1 Buring, Julie 1 Canzian, Federico 1 Chaffee, Kari G 1 Chanock, Stephen 1 Childs, Erica J 1 Cleary, Sean 1
- Organizace
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Pracoviště
CIBER Epidemiología y Salud Pública U... 1 CIBERONC Madrid Spain Epithelial Carc... 1 Cancer Care Ontario University of Tor... 1 Cancer Epidemiology Program Universit... 1 Cancer Epidemiology and Intelligence ... 1 Cancer Epidemiology and Intelligence ... 1 Cancer Epidemiology and Intelligence ... 1 Centre de Recherche en Épidémiologie ... 1 Department for Determinants of Chroni... 1 Department of Cancer Epidemiology and... 1 Department of Chronic Disease Epidemi... 1 Department of Epidemiology Harvard T ... 1 Department of Epidemiology Johns Hopk... 1 Department of Epidemiology University... 1 Department of Epidemiology and Biosta... 1 Department of Epidemiology and Biosta... 1 Department of Epidemiology and Enviro... 1 Department of Epidemiology and Public... 1 Department of Gastrointestinal Medica... 1 Department of General Surgery Univers... 1
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- Walsh, Naomi
- Zhang, Han
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Hyland, Paula L
Autor Hyland, Paula L Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. Division of Applied Regulatory Science, Office of Translational Science, Center for Drug Evaluation & Research, U.S. Food and Drug Administration, Silver Spring, MD
- Yang, Qi
- Mocci, Evelina
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Zhang, Mingfeng
Autor Zhang, Mingfeng Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. Division of Epidemiology II, Office of Surveillance and Epidemiology, Center for Drug Evaluation & Research, U.S. Food and Drug Administration, Silver Spring, MD
- Childs, Erica J
- Collins, Irene
- Wang, Zhaoming
- Arslan, Alan A
NLK
Free Medical Journals
od 1996 do Před 1 rokem
Open Access Digital Library
od 1996-01-01
PubMed
30541042
DOI
10.1093/jnci/djy155
Knihovny.cz E-zdroje
BACKGROUND: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. METHODS: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. RESULTS: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets. CONCLUSION: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
- MeSH
- celogenomová asociační studie metody MeSH
- duktální karcinom pankreatu genetika MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- nádory slinivky břišní genetika MeSH
- statistické modely MeSH
- studie případů a kontrol MeSH
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- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
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