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....
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1828439321140527104 |
---|---|
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. |
first_indexed | 2024-12-10T20:20:57Z |
format | Article |
id | doaj.art-2c4790d40a374002b61e524278d50613 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-10T20:20:57Z |
publishDate | 2015-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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 |
work_keys_str_mv | AT katarinalagergren polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT weronicaeek polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT davidlevine polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT wonghochow polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT lesliebernstein polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT alangcasson polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT harveyarisch polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT nicholasjshaheen polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT nigelcbird polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT brianjreid polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT douglasacorley polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT laurajhardie polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT annahwu polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT rebeccacfitzgerald polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT paulpharoah polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT carloscaldas polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT yvonneromero polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT thomaslvaughan polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT stuartmacgregor polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT davidwhiteman polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT larswestberg polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT olofnyren polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium AT jesperlagergren polymorphismsingenesofrelevanceforoestrogenandoxytocinpathwaysandriskofbarrettsoesophagusandoesophagealadenocarcinomaapooledanalysisfromthebeaconconsortium |