• Login
    View Item 
    •   Home
    • Sherwood Forest Hospitals NHS Foundation Trust
    • Medicine Division
    • Gastroenterology and Hepatology Services
    • View Item
    •   Home
    • Sherwood Forest Hospitals NHS Foundation Trust
    • Medicine Division
    • Gastroenterology and Hepatology Services
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of EMERCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjectsProfilesView

    My Account

    LoginRegister

    Links

    About EMERPoliciesDerbyshire Community Health Services NHS Foundation TrustLeicester Partnership TrustNHS Nottingham and Nottinghamshire CCGNottinghamshire Healthcare NHS Foundation TrustNottingham University Hospitals NHS TrustSherwood Forest Hospitals NHS Foundation TrustUniversity Hospitals of Derby and Burton NHS Foundation TrustUniversity Hospitals Of Leicester NHS TrustOther Resources

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Germline variation in the ...
    Size:
    1.924Mb
    Format:
    PDF
    Download
    Author
    Jankowski, Janusz
    Keyword
    Adenocarcinoma
    Barrett esophagus
    Biomarkers
    Esophageal
    Risk factors
    Date
    2021-04
    
    Metadata
    Show full item record
    Publisher's URL
    https://academic.oup.com/carcin/article/42/3/369/6029419
    Abstract
    Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
    Citation
    Dighe, S. G. et al. (2021) ‘Germline variation in the insulin-like growth factor pathway and risk of Barrett’s esophagus and esophageal adenocarcinoma’, Carcinogenesis, 42(3), pp. 369–377
    Publisher
    Carcinogenisis
    Type
    Article
    URI
    http://hdl.handle.net/20.500.12904/15146
    Collections
    Gastroenterology and Hepatology Services

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.