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.
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.
Authors: Juliët H Hoff; Rene H M te Morsche; Hennie M J Roelofs; Elise M J van der Logt; Fokko M Nagengast; Wilbert H M Peters Journal: World J Gastroenterol Date: 2009-09-28 Impact factor: 5.742
Authors: James Y Dai; Jean de Dieu Tapsoba; Matthew F Buas; Lynn E Onstad; David M Levine; Harvey A Risch; Wong-Ho Chow; Leslie Bernstein; Weimin Ye; Jesper Lagergren; Nigel C Bird; Douglas A Corley; Nicholas J Shaheen; Anna H Wu; Brian J Reid; Laura J Hardie; David C Whiteman; Thomas L Vaughan Journal: Cancer Epidemiol Biomarkers Prev Date: 2015-09-16 Impact factor: 4.254
Authors: Vincent T Janmaat; Anouk Van De Winkel; Maikel P Peppelenbosch; Manon C W Spaander; André G Uitterlinden; Farzin Pourfarzad; Hugo W Tilanus; Agnieszka M Rygiel; Leon M G Moons; Pascal P Arp; Kausilia K Krishnadath; Ernst J Kuipers; Luc J W Van Der Laan Journal: Mol Med Date: 2015-04-21 Impact factor: 6.354
Authors: Jón O Kristinsson; Paul van Westerveld; Rene H M te Morsche; Hennie M J Roelofs; T Wobbes; Ben J M Witteman; Adriaan C I T L Tan; Martijn G H van Oijen; Jan B M J Jansen; Wilbert H M Peters Journal: World J Gastroenterol Date: 2009-07-28 Impact factor: 5.742