COX-2 CA-haplotype is a risk factor for the development of esophageal adenocarcinoma.
| Autor: | Moons LM; Department of Gastroenterology and Hepatology, Erasmus MC- University Medical Center Rotterdam, Rotterdam, The Netherlands., Kuipers EJ, Rygiel AM, Groothuismink AZ, Geldof H, Bode WA, Krishnadath KK, Bergman JJ, van Vliet AH, Siersema PD, Kusters JG |
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| Jazyk: | angličtina |
| Zdroj: | The American journal of gastroenterology [Am J Gastroenterol] 2007 Nov; Vol. 102 (11), pp. 2373-9. Date of Electronic Publication: 2007 Jun 20. |
| DOI: | 10.1111/j.1572-0241.2007.01373.x |
| Abstrakt: | 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: | MEDLINE |
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