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Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract pp 265–290Cite as

Common Variants Confer Susceptibility to Barrett’s Esophagus: Insights from the First Genome-Wide Association Studies

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 908))

Abstract

Eight loci have been identified by the two genome-wide association studies of Barrett’s esophagus that have been conducted to date. Esophageal adenocarcinoma cases were included in the second study following evidence that predisposing genetic variants for this cancer overlap with those for Barrett’s esophagus. Genes with roles in embryonic development of the foregut are adjacent to 6 of the loci identified (FOXF1, BARX1, FOXP1, GDF7, TBX5, and ALDH1A2). An additional locus maps to a gene with known oncogenic potential (CREB-regulated transcription coactivator 1), but expression quantitative trait data implicates yet another gene involved in esophageal development (PBX4). These results strongly support a model whereby dysregulation of genes involved in esophageal and thoracic development increases susceptibility to Barrett’s esophagus and esophageal adenocarcinoma, probably by reducing anatomical antireflux mechanisms. An additional signal at 6p21 in the major histocompatibility complex also reinforces evidence that immune and inflammatory response to reflux is involved in the development of both diseases. All of the variants identified are intronic or intergenic rather than coding and are presumed to be or to mark regulatory variants. As with genome-wide association studies of other diseases, the functional variants at each locus are yet to be identified and the genes affected need confirming. In this chapter as well as discussing the biology behind each genome-wide association signal, we review the requirements for successfully conducting genome-wide association studies and discuss how progress in understanding the genetic variants that contribute to Barrett’s esophagus/esophageal adenocarcinoma susceptibility compares to other cancers.

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Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Claire Palles, John M. Findlay & Ian Tomlinson

  2. NIHR Oxford Biomedical Research Centre, Churchill Hospital, Old Road, Oxford, OX3 7LE, UK

    John M. Findlay

  3. Oxford OesophagoGastric Centre, Churchill Hospital, Old Road, Oxford, OX3 7LE, UK

    John M. Findlay

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  1. Claire Palles
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Correspondence to Claire Palles .

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Editors and Affiliations

  1. UCL Cancer Institute, University College London, London, United Kingdom

    Marnix Jansen

  2. Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom

    Nicholas A. Wright

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Palles, C., Findlay, J.M., Tomlinson, I. (2016). Common Variants Confer Susceptibility to Barrett’s Esophagus: Insights from the First Genome-Wide Association Studies. In: Jansen, M., Wright, N. (eds) Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract. Advances in Experimental Medicine and Biology, vol 908. Springer, Cham. https://doi.org/10.1007/978-3-319-41388-4_13

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