1. COX-2 CA-haplotype is a risk factor for the development of esophageal adenocarcinoma
- Author
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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, Center of Experimental and Molecular Medicine, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, and Gastroenterology and Hepatology
- Subjects
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 - Abstract
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.
- Published
- 2007
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