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Int J Cancer. 2016 Mar 1;138(5):1146-52. doi: 10.1002/ijc.29863. Epub 2015 Oct 5.

Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Author information

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

Abstract

The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p = 0.002) and in males (p = 0.003), but not in females separately (p = 0.3). This association was found in tobacco smokers (p = 0.003) and in BE patients without reflux (p = 0.004), but not in nonsmokers (p = 0.2) or those with reflux (p = 0.036). SNPs within JMJD1C were associated with risk of EAC in females (p = 0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.

KEYWORDS:

Barrett esophagus; esophageal neoplasms; genome-wide association study; gonadal steroid hormone; hormones; neoplasm

PMID:
26414697
PMCID:
PMC4715576
[Available on 2017-03-01]
DOI:
10.1002/ijc.29863
[Indexed for MEDLINE]
Free PMC Article

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