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PLoS One. 2015 Sep 25;10(9):e0138738. doi: 10.1371/journal.pone.0138738. eCollection 2015.

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.

Author information

1
Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
2
Statistical Genetics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala, Sweden.
3
Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
4
Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas, United States of America.
5
Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California, United States of America.
6
Department of Surgery, University of Saskatchewan, Saskatoon, SK, Canada.
7
Yale School of Public Health, New Haven, Connecticut, United States of America.
8
Division of Gastroenterology and Hepatology, UNC School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
9
Department of Oncology, The Medical School, University of Sheffield, Sheffield, United Kingdom.
10
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
11
Kaiser Permanente Northern California, Division of Research, Oakland, California, United States of America.
12
Division of Epidemiology, University of Leeds, Leeds, United Kingdom.
13
Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
14
Medical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, United Kingdom.
15
Department of Public Health, University of Cambridge, Cambridge, United Kingdom.
16
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
17
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States of America.
18
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
19
Statistical Genetics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
20
Cancer Control Group, Queensland Institute of Medical Research, Herston, Queensland, Australia.
21
Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
22
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
23
Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Division of Cancer Studies, King's College London, London, United Kingdom.

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.

PMID:
26406593
PMCID:
PMC4583498
DOI:
10.1371/journal.pone.0138738
[Indexed for MEDLINE]
Free PMC Article

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