Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett’s Esophagus
Creators: name: Al Dulaimi, David
name: Johnson, Matthew
name: Trynka, Gosia
name: Prenen, Hans
name: Atherfold, Paul
name: Li, Xinzhong
name: Vaughan, Tom L.
name: Ye, Weimin
name: Love, Sharon
name: Van Der Laan, Luc J.W.
name: Boulter, Lisa
name: Rathbone, Barrie
name: Shaheen, Nicholas J.
name: Underwood, Tim
name: Decaestecker, John
name: Roylance, Rebecca
name: Chow, Wu
name: Reid, Brian J.
name: Van Den Brande, Jan
name: Watson, Peter
name: Ang, Yeng
name: Monk, David
name: Bisschops, Raf
name: Farrant, Mark
name: Farnham, Garry
name: O'Sullivan, Jacintha
name: Dhar, Anjan
name: Bernstein, Leslie
name: Beales, Ian
name: Toxopeus, Eelke L.
name: Wijmenga, Cisca
name: Hapeshi, Julie
name: Tucker, Art
name: Sanders, Scott
name: Nwokolo, Chuka
name: Moayyedi, Paul
name: Kadri, Sudarshan
name: Vermeire, Severine
name: Bird, Nigel C.
name: Barr, Hugh
name: Ragunath, Krish
name: Gammon, Marilie D.
name: Liu, Geoffrey
name: Briggs, Sarah
name: Castro Giner, Francesc
name: Harrison, Rebecca
name: Romero, Yvonne
name: Patel, Praful
name: Kelly, Sean
name: Krishnadath, Kausilia
name: Casson, Alan G.
name: Cleynen, Isabelle
name: Macdonald, David
name: Beckett, Conrad
name: McGarrigle, Sarah A.
name: Adams, Claire L.
name: Fitzgerald, Rebecca
name: Reynolds, John V.
name: Dixon, Andrew
name: Whiteman, David C.
name: Kuipers, Ernst J.
name: McManus, Ross
name: Wu, Anna H.
name: Tomlinson, Ian
name: Wijnhoven, Bas P.L.
name: Zietek, Barbara
name: Risch, Harvey A.
name: Chegwidden, Laura
name: Rembacken, Bjorn
name: Mullins, Paul
name: Haigh, Chris
name: Corley, Douglas A.
name: Verhaar, Auke P.
name: Trudgill, Nigel
name: Ferry, David
name: Palles, Claire
name: Murray, Iain
name: Green, Elaine
name: Nanji, Manoj
name: Levine, David M.
name: Maroo, Neera
name: Spaander, Manon C.
name: Wajed, Shahjehan
name: Kovac, Michal
name: Sawyer, Elinor
name: McMurtry, Hugh
name: Hardie, Laura J.
name: Gay, Laura
name: Findlay, John M.
name: Paterson, Stuart
name: Peppelenbosch, Maikel P.
name: Veitch, Andrew
name: Grimley, Charles
name: Macmathuna, Padraic
name: Onstad, Lynn
name: Koss, Konrad
name: Kelleher, Dermot
name: Jankowski, Janusz
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2015

description: Background & AimsBarrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.MethodsWe performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.ResultsWe identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR]= 1.14; 95% CI: 1.09–1.18; P= 1.8× 10−11) and rs2701108 (12q24.21; OR= 0.90; 95% CI: 0.86–0.93; P= 7.5× 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNPassociated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR= 0.90; 95% CI: 0.87–0.93; P=3.72× 10−9).ConclusionsWe identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.