| Cyclooxygenase-2 and inducible nitric oxide synthase gene polymorphisms and risk of reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. | |
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MedLine Citation:
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PMID: 18349295 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The incidence of esophageal adenocarcinoma has increased in recent years, and Barrett's esophagus is a recognized risk factor. Gastroesophageal reflux of acid and/or bile is linked to these conditions and to reflux esophagitis. Inflammatory disorders can lead to carcinogenesis through activation of "prosurvival genes," including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Increased expression of these enzymes has been found in esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Polymorphic variants in COX-2 and iNOS genes may be modifiers of risk of these conditions. In a population-based case-control study, we examined associations of the COX-2 8473 T>C and iNOS Ser(608) Leu (C>T) polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), and reflux esophagitis (n = 230) and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using TaqMan allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. The presence of at least one COX-2 8473 C allele was associated with a significantly increased risk of esophageal adenocarcinoma (adjusted odds ratio, 1.58; 95% confidence interval, 1.04-2.40). There was no significant association between this polymorphism and risk of Barrett's esophagus or reflux esophagitis or between the iNOS Ser 608 Leu polymorphism and risk of these esophageal conditions. Our study suggests that the COX-2 8473 C allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma. |
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Authors:
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Heather R Ferguson; Christopher P Wild; Lesley A Anderson; Seamus J Murphy; Brian T Johnston; Liam J Murray; R G Peter Watson; Jim McGuigan; John V Reynolds; Laura J Hardie |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Volume: 17 ISSN: 1055-9965 ISO Abbreviation: Cancer Epidemiol. Biomarkers Prev. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-03-19 Completed Date: 2008-06-17 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9200608 Medline TA: Cancer Epidemiol Biomarkers Prev Country: United States |
Other Details:
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Languages: eng Pagination: 727-31 Citation Subset: IM |
Affiliation:
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Division of Gastroenterology, Belfast City Hospital, Belfast, United Kingdom. hrferguson@doctors.net.uk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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enzymology*,
genetics* Alleles Barrett Esophagus / enzymology*, genetics* Case-Control Studies Cyclooxygenase 2 / genetics* Esophageal Neoplasms / enzymology*, genetics* Esophagitis, Peptic / enzymology*, genetics* Female Genetic Markers Genetic Variation Humans Logistic Models Male Middle Aged Nitric Oxide Synthase Type II / genetics* Polymorphism, Genetic* |
| Chemical | |
Reg. No./Substance:
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0/Genetic Markers; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.99.1/Cyclooxygenase 2 |
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