Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America....

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Main Authors: Katarina Lagergren, Weronica E Ek, David Levine, Wong-Ho Chow, Leslie Bernstein, Alan G Casson, Harvey A Risch, Nicholas J Shaheen, Nigel C Bird, Brian J Reid, Douglas A Corley, Laura J Hardie, Anna H Wu, Rebecca C Fitzgerald, Paul Pharoah, Carlos Caldas, Yvonne Romero, Thomas L Vaughan, Stuart MacGregor, David Whiteman, Lars Westberg, Olof Nyren, Jesper Lagergren
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4583498?pdf=render
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author Katarina Lagergren
Weronica E Ek
David Levine
Wong-Ho Chow
Leslie Bernstein
Alan G Casson
Harvey A Risch
Nicholas J Shaheen
Nigel C Bird
Brian J Reid
Douglas A Corley
Laura J Hardie
Anna H Wu
Rebecca C Fitzgerald
Paul Pharoah
Carlos Caldas
Yvonne Romero
Thomas L Vaughan
Stuart MacGregor
David Whiteman
Lars Westberg
Olof Nyren
Jesper Lagergren
author_facet Katarina Lagergren
Weronica E Ek
David Levine
Wong-Ho Chow
Leslie Bernstein
Alan G Casson
Harvey A Risch
Nicholas J Shaheen
Nigel C Bird
Brian J Reid
Douglas A Corley
Laura J Hardie
Anna H Wu
Rebecca C Fitzgerald
Paul Pharoah
Carlos Caldas
Yvonne Romero
Thomas L Vaughan
Stuart MacGregor
David Whiteman
Lars Westberg
Olof Nyren
Jesper Lagergren
author_sort Katarina Lagergren
collection DOAJ
description The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS).Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only.Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.
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spelling doaj.art-2c4790d40a374002b61e524278d506132022-12-22T01:35:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013873810.1371/journal.pone.0138738Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.Katarina LagergrenWeronica E EkDavid LevineWong-Ho ChowLeslie BernsteinAlan G CassonHarvey A RischNicholas J ShaheenNigel C BirdBrian J ReidDouglas A CorleyLaura J HardieAnna H WuRebecca C FitzgeraldPaul PharoahCarlos CaldasYvonne RomeroThomas L VaughanStuart MacGregorDavid WhitemanLars WestbergOlof NyrenJesper LagergrenThe strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS).Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only.Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.http://europepmc.org/articles/PMC4583498?pdf=render
spellingShingle Katarina Lagergren
Weronica E Ek
David Levine
Wong-Ho Chow
Leslie Bernstein
Alan G Casson
Harvey A Risch
Nicholas J Shaheen
Nigel C Bird
Brian J Reid
Douglas A Corley
Laura J Hardie
Anna H Wu
Rebecca C Fitzgerald
Paul Pharoah
Carlos Caldas
Yvonne Romero
Thomas L Vaughan
Stuart MacGregor
David Whiteman
Lars Westberg
Olof Nyren
Jesper Lagergren
Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.
PLoS ONE
title Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.
title_full Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.
title_fullStr Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.
title_full_unstemmed Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.
title_short Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.
title_sort polymorphisms in genes of relevance for oestrogen and oxytocin pathways and risk of barrett s oesophagus and oesophageal adenocarcinoma a pooled analysis from the beacon consortium
url http://europepmc.org/articles/PMC4583498?pdf=render
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