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- Title
COX-2 CA-Haplotype Is a Risk Factor for the Development of Esophageal Adenocarcinoma.
- Authors
Moons, Leon M. G.; Kuipers, Ernst J.; Rygiel, Agnieszka M.; Groothuismink, Anthonie Z. M.; Geldof, Han; Bode, Willem A.; Krishnadath, Kausilia K.; Bergman, Jacques J. G. H. M.; van Vliet, Arnoud H. M.; Siersema, Peter D.; Kusters, Johannes G.
- 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.
- Subjects
CLINICAL trials; CYCLOOXYGENASE 2; ADENOCARCINOMA; GASTROESOPHAGEAL reflux; ESOPHAGUS diseases; GENETIC polymorphisms; GENE expression; GENETICS; DISEASE risk factors
- Publication
American Journal of Gastroenterology (Springer Nature), 2007, Vol 102, Issue 11, p2373
- ISSN
0002-9270
- Publication type
Article
- DOI
10.1111/j.1572-0241.2007.01373.x