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- 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.
- Authors
Lagergren, Katarina; Ek, Weronica E.; Levine, David; Chow, Wong-Ho; Bernstein, Leslie; Casson, Alan G.; Risch, Harvey A.; Shaheen, Nicholas J.; Bird, Nigel C.; Reid, Brian J.; Corley, Douglas A.; Hardie, Laura J.; Wu, Anna H.; Fitzgerald, Rebecca C.; Pharoah, Paul; Caldas, Carlos; Romero, Yvonne; Vaughan, Thomas L.; MacGregor, Stuart; Whiteman, David
- 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.
- Subjects
GENETIC polymorphisms; ESTROGEN; OXYTOCIN; ADENOCARCINOMA; ESOPHAGEAL cancer
- Publication
PLoS ONE, 2015, Vol 10, Issue 9, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0138738