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- W2517588953 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." @default.
- W2517588953 created "2016-09-16" @default.
- W2517588953 creator A5004647151 @default.
- W2517588953 creator A5040598662 @default.
- W2517588953 creator A5054985161 @default.
- W2517588953 date "2016-01-01" @default.
- W2517588953 modified "2023-09-27" @default.
- W2517588953 title "Common Variants Confer Susceptibility to Barrett’s Esophagus: Insights from the First Genome-Wide Association Studies" @default.
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