Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

2.50
Hdl Handle:
http://hdl.handle.net/11287/593934
Title:
Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus
Authors:
Palles, C.; Chegwidden, L.; Li, X.; Findlay, J. M.; Farnham, G.; Castro Giner, F.; Peppelenbosch, M. P.; Kovac, M.; Adams, C. L.; Prenen, H.; Briggs, S.; Harrison, R.; Sanders, S.; MacDonald, D.; Haigh, C.; Tucker, A.; Love, S.; Nanji, M.; deCaestecker, J.; Ferry, D.; Rathbone, B.; Hapeshi, J.; Barr, H.; Moayyedi, P.; Watson, P.; Zietek, B.; Maroo, N.; Gay, L.; Underwood, T.; Boulter, L.; McMurtry, H.; Monk, D.; Patel, P.; Ragunath, K.; Al Dulaimi, D.; Murray, I.; Koss, K.; Veitch, A.; Trudgill, N.; Nwokolo, C.; Rembacken, B.; Atherfold, P.; Green, E.; Ang, Y.; Kuipers, E. J.; Chow, W.; Paterson, S.; Kadri, S.; Beales, I.; Grimley, C.; Mullins, P.; Beckett, C.; Farrant, M.; Dixon, A.; Kelly, S.; Johnson, Matthew; Wajed, Shahjehan; Dhar, A.; Sawyer, E.; Roylance, R.; Onstad, L.; Gammon, M. D.; Corley, D. A.; Shaheen, N. J.; Bird, N. C.; Hardie, L. J.; Reid, B. J.; Ye, W.; Liu, G.; Romero, Y.; Bernstein, L.; Wu, A. H.; Casson, A. G.; Fitzgerald, R.; Whiteman, D. C.; Risch, H. A.; Levine, D. M.; Vaughan, T. L.; Verhaar, A. P.; van den Brande, J.; Toxopeus, E. L.; Spaander, M. C.; Wijnhoven, B. P.; van der Laan, L. J.; Krishnadath, K.; Wijmenga, C.; Trynka, G.; McManus, R.; Reynolds, J. V.; O'Sullivan, J.; MacMathuna, P.; McGarrigle, S. A.; Kelleher, D.; Vermeire, S.; Cleynen, I.; Bisschops, R.; Tomlinson, I.; Jankowski, J.
Abstract:
BACKGROUND & AIMS: Barrett'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. METHODS: We 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. RESULTS: We 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 x 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 x 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 SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 x 10(-9)). CONCLUSIONS: We 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.
Citation:
Gastroenterology. 2015 Feb;148(2):367-78.
Publisher:
Elsevier
Journal:
Gastroenterology
Issue Date:
1-Feb-2015
URI:
http://hdl.handle.net/11287/593934
DOI:
10.1053/j.gastro.2014.10.041
PubMed ID:
25447851
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0016-5085(14)01334-1
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1528-0012
Appears in Collections:
2015 RD&E publications; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorPalles, C.en
dc.contributor.authorChegwidden, L.en
dc.contributor.authorLi, X.en
dc.contributor.authorFindlay, J. M.en
dc.contributor.authorFarnham, G.en
dc.contributor.authorCastro Giner, F.en
dc.contributor.authorPeppelenbosch, M. P.en
dc.contributor.authorKovac, M.en
dc.contributor.authorAdams, C. L.en
dc.contributor.authorPrenen, H.en
dc.contributor.authorBriggs, S.en
dc.contributor.authorHarrison, R.en
dc.contributor.authorSanders, S.en
dc.contributor.authorMacDonald, D.en
dc.contributor.authorHaigh, C.en
dc.contributor.authorTucker, A.en
dc.contributor.authorLove, S.en
dc.contributor.authorNanji, M.en
dc.contributor.authordeCaestecker, J.en
dc.contributor.authorFerry, D.en
dc.contributor.authorRathbone, B.en
dc.contributor.authorHapeshi, J.en
dc.contributor.authorBarr, H.en
dc.contributor.authorMoayyedi, P.en
dc.contributor.authorWatson, P.en
dc.contributor.authorZietek, B.en
dc.contributor.authorMaroo, N.en
dc.contributor.authorGay, L.en
dc.contributor.authorUnderwood, T.en
dc.contributor.authorBoulter, L.en
dc.contributor.authorMcMurtry, H.en
dc.contributor.authorMonk, D.en
dc.contributor.authorPatel, P.en
dc.contributor.authorRagunath, K.en
dc.contributor.authorAl Dulaimi, D.en
dc.contributor.authorMurray, I.en
dc.contributor.authorKoss, K.en
dc.contributor.authorVeitch, A.en
dc.contributor.authorTrudgill, N.en
dc.contributor.authorNwokolo, C.en
dc.contributor.authorRembacken, B.en
dc.contributor.authorAtherfold, P.en
dc.contributor.authorGreen, E.en
dc.contributor.authorAng, Y.en
dc.contributor.authorKuipers, E. J.en
dc.contributor.authorChow, W.en
dc.contributor.authorPaterson, S.en
dc.contributor.authorKadri, S.en
dc.contributor.authorBeales, I.en
dc.contributor.authorGrimley, C.en
dc.contributor.authorMullins, P.en
dc.contributor.authorBeckett, C.en
dc.contributor.authorFarrant, M.en
dc.contributor.authorDixon, A.en
dc.contributor.authorKelly, S.en
dc.contributor.authorJohnson, Matthewen
dc.contributor.authorWajed, Shahjehanen
dc.contributor.authorDhar, A.en
dc.contributor.authorSawyer, E.en
dc.contributor.authorRoylance, R.en
dc.contributor.authorOnstad, L.en
dc.contributor.authorGammon, M. D.en
dc.contributor.authorCorley, D. A.en
dc.contributor.authorShaheen, N. J.en
dc.contributor.authorBird, N. C.en
dc.contributor.authorHardie, L. J.en
dc.contributor.authorReid, B. J.en
dc.contributor.authorYe, W.en
dc.contributor.authorLiu, G.en
dc.contributor.authorRomero, Y.en
dc.contributor.authorBernstein, L.en
dc.contributor.authorWu, A. H.en
dc.contributor.authorCasson, A. G.en
dc.contributor.authorFitzgerald, R.en
dc.contributor.authorWhiteman, D. C.en
dc.contributor.authorRisch, H. A.en
dc.contributor.authorLevine, D. M.en
dc.contributor.authorVaughan, T. L.en
dc.contributor.authorVerhaar, A. P.en
dc.contributor.authorvan den Brande, J.en
dc.contributor.authorToxopeus, E. L.en
dc.contributor.authorSpaander, M. C.en
dc.contributor.authorWijnhoven, B. P.en
dc.contributor.authorvan der Laan, L. J.en
dc.contributor.authorKrishnadath, K.en
dc.contributor.authorWijmenga, C.en
dc.contributor.authorTrynka, G.en
dc.contributor.authorMcManus, R.en
dc.contributor.authorReynolds, J. V.en
dc.contributor.authorO'Sullivan, J.en
dc.contributor.authorMacMathuna, P.en
dc.contributor.authorMcGarrigle, S. A.en
dc.contributor.authorKelleher, D.en
dc.contributor.authorVermeire, S.en
dc.contributor.authorCleynen, I.en
dc.contributor.authorBisschops, R.en
dc.contributor.authorTomlinson, I.en
dc.contributor.authorJankowski, J.en
dc.date.accessioned2016-01-19T12:37:34Zen
dc.date.available2016-01-19T12:37:34Zen
dc.date.issued2015-02-01en
dc.identifier.citationGastroenterology. 2015 Feb;148(2):367-78.en
dc.identifier.issn1528-0012en
dc.identifier.pmid25447851en
dc.identifier.doi10.1053/j.gastro.2014.10.041en
dc.identifier.urihttp://hdl.handle.net/11287/593934en
dc.description.abstractBACKGROUND & AIMS: Barrett'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. METHODS: We 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. RESULTS: We 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 x 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 x 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 SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 x 10(-9)). CONCLUSIONS: We 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.en
dc.language.isoengen
dc.publisherElsevieren
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0016-5085(14)01334-1en
dc.titlePolymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagusen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalGastroenterologyen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

Related articles on PubMed

All Items in RD&E Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.