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Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.
- Source :
-
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association [Clin Gastroenterol Hepatol] 2018 Oct; Vol. 16 (10), pp. 1598-1606.e4. Date of Electronic Publication: 2018 Mar 15. - Publication Year :
- 2018
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Abstract
- Background & Aims: Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and BE. Genetic factors might interact with environmental factors to affect risk of EA and BE. We aimed to identify single nucleotide polymorphisms (SNPs) that may modify the associations of body mass index (BMI), smoking, and gastroesophageal reflux disease (GERD), with risks of EA and BE.<br />Methods: We collected data on single BMI measurements, smoking status, and symptoms of GERD from 2284 patients with EA, 3104 patients with BE, and 2182 healthy individuals (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium GWAS, the UK Barrett's Esophagus Gene Study, and the UK Stomach and Oesophageal Cancer Study. We analyzed 993,501 SNPs in DNA samples of all study subjects. We used standard case-control logistic regression to test for gene-environment interactions.<br />Results: For EA, rs13429103 at chromosome 2p25.1, near the RNF144A-LOC339788 gene, showed a borderline significant interaction with smoking status (P = 2.18×10 <superscript>-7</superscript> ). Ever smoking was associated with an almost 12-fold increase in risk of EA among individuals with rs13429103-AA genotype (odds ratio=11.82; 95% CI, 4.03-34.67). Three SNPs (rs12465911, rs2341926, rs13396805) at chromosome 2q23.3, near the RND3-RBM43 gene, interacted with GERD symptoms (P = 1.70×10 <superscript>-7</superscript> , P = 1.83×10 <superscript>-7</superscript> , and P = 3.58×10 <superscript>-7</superscript> , respectively) to affect risk of EA. For BE, rs491603 at chromosome 1p34.3, near the EIF2C3 gene, and rs11631094 at chromosome 15q14, at the SLC12A6 gene, interacted with BMI (P = 4.44×10 <superscript>-7</superscript> ) and pack-years of smoking history (P = 2.82×10 <superscript>-7</superscript> ), respectively.<br />Conclusion: The associations of BMI, smoking, and GERD symptoms with risks of EA and BE appear to vary with SNPs at chromosomes 1, 2, and 15. Validation of these suggestive interactions is warranted.<br /> (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adenocarcinoma etiology
Aged
Esophageal Neoplasms etiology
Female
Genome-Wide Association Study
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Risk Assessment
United Kingdom epidemiology
Adenocarcinoma epidemiology
Barrett Esophagus complications
Barrett Esophagus epidemiology
Environmental Exposure
Esophageal Neoplasms epidemiology
Genetic Predisposition to Disease
Subjects
Details
- Language :
- English
- ISSN :
- 1542-7714
- Volume :
- 16
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
- Publication Type :
- Academic Journal
- Accession number :
- 29551738
- Full Text :
- https://doi.org/10.1016/j.cgh.2018.03.007