COX-2 CA-haplotype is a risk factor for the development of esophageal adenocarcinoma
| Autor: | Kausilia K. Krishnadath, Anthonie Z. M. Groothuismink, Ernst J. Kuipers, Willem A. Bode, Jacques J. Bergman, Arnoud H. M. van Vliet, Johannes G. Kusters, Han Geldof, Agnieszka M. Rygiel, Peter D. Siersema, Leon M G Moons |
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| Přispěvatelé: | Center of Experimental and Molecular Medicine, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, Gastroenterology and Hepatology |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Esophageal Neoplasms Genotype Population Adenocarcinoma Gastroenterology law.invention Barrett Esophagus law Risk Factors Internal medicine medicine Humans Genetic Predisposition to Disease Reflux esophagitis Risk factor education Esophagitis Peptic Polymerase chain reaction Alleles Aged Netherlands education.field_of_study Chi-Square Distribution Polymorphism Genetic Hepatology Esophageal disease business.industry Haplotype Reflux Middle Aged medicine.disease Logistic Models Haplotypes Cyclooxygenase 2 Disease Progression Female Esophagoscopy business Esophagitis |
| Zdroj: | American journal of gastroenterology, 102(11), 2373-2379. Springer Nature |
| ISSN: | 0002-9270 |
| Popis: | BACKGROUND: Neoplastic progression of BE towards EAC is associated with increased expression of COX-2. Increased COX-2 expression and enzyme activity is linked to the COX-2 CA haplotype, which consists of two gene polymorphisms in the COX-2 promoter. AIM: To study the impact of COX-2 haplotypes on the risk of developing EAC in patients with different forms of gastroesophageal reflux disease including BE. METHODS: DNA was obtained from a total of 635 Dutch white patients comprised of 140 patients with EAC, 255 with BE, and 240 with reflux esophagitis. COX-2 haplotypes were based on the gene polymorphisms at -765C/G and -1195A/G, as determined by PCR-RFLP. RESULTS: The tested population contained 170 (14%) CA- (-765C and -1195A) haplotypes, 829 (65%) GA and 271 (21%) GG-haplotypes, and no GC-haplotypes. The haplotype distribution in patients with reflux esophagitis and BE was similar (CA 12%, GA 68%, GG 21%), but differed significantly from that in patients with EAC (CA 21%, GA 58%, GG 20%). Particularly, the CA-haplotype was more common (P < 0.001) in EAC patients. CA-carriership was associated with EAC (OR 2.8, 95% CI 1.3-6.2, P = 0.008), with homozygosity for the CA-allele being statistically most significantly associated (OR 6.1, 95% CI 1.6-24.2, P = 0.01). CONCLUSION: The COX-2 CA-haplotype is more frequently observed in patients with EAC than in patients with BE and reflux esophagitis. These data suggest a direct link between COX-2 activity and neoplastic progression in patients with BE and reflux esophagitis. |
| Databáze: | OpenAIRE |
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