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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.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Lagergren, Katarina 
Ek, Weronica E 
Levine, David 
Chow, Wong-Ho 
Bernstein, Leslie 

Abstract

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Description

Keywords

ADP-ribosyl Cyclase 1, Adenocarcinoma, Aromatase, Barrett Esophagus, Esophageal Neoplasms, Estrogen Receptor alpha, Estrogen Receptor beta, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Membrane Glycoproteins, Oxytocin, Polymorphism, Single Nucleotide, Receptors, Oxytocin, Sex Factors

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

10

Publisher

Public Library of Science (PLoS)

Rights

CC0 No rights reserved
Sponsorship
National Institute of Diabetes and Digestive and Kidney Diseases (K24DK100548)