Neoplastic progression of Barrett's Esophagus towards esophageal adenocarcinoma is associated with increased expression of cyclooxygenase-2 (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.
Dr Johannes Kuster and colleagues from the Netherlands studied the impact of COX-2 haplotypes on the risk of developing esophageal adenocarcinoma in patients with different forms of gastroesophageal reflux disease (GERD) including Barrett's Esophagus.
|CA-carriership was associated with esophageal adenocarcinoma|
|The American Journal of Gastroenterology|
The team obtained DNA from a total of 635 Dutch white patients comprised of 140 patients with esophageal adenocarcinoma, 255 with Barrett's Esophagus, and 240 with reflux esophagitis.
COX-2 haplotypes were based on the gene polymorphisms at -765C/G and -1195A/G.
The researchers reported that the tested population contained 170 CA- (-765C and -1195A) haplotypes, 829 GA and 271 GG-haplotypes, and no GC-haplotypes.
The haplotype distribution in patients with reflux esophagitis and Barrett's Esophagus was similar.
The research team observed that the haplotype distribution in patients with esophageal adenocarcinoma differed significantly from those with reflux esophagitis and Barrett's Esophagus.
The team found that the CA-haplotype was more common in esophageal adenocarcinoma patients.
CA-carriership was associated with esophageal adenocarcinoma.
The team noted that homozygosity for the CA-allele was statistically most significantly associated with esophageal adenocarcinoma.
Dr Moons' team concluded, "The COX-2 CA-haplotype is more frequently observed in patients with EAC than in patients with Barrett's Esophagus and reflux esophagitis."
"These data suggest a direct link between COX-2 activity and neoplastic progression in patients with Barrett's Esophagus and reflux esophagitis."