COX-2 CA-haplotype is a risk factor for the development of esophageal adenocarcinoma.
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.


OBJECTIVE
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).


CONCLUSIONS
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.
Moons
Leon M G
LM
Department of Gastroenterology and Hepatology, Erasmus MC- University Medical Center Rotterdam, Rotterdam, The Netherlands.
Kuipers
Ernst J
EJ
Rygiel
Agnieszka M
AM
Groothuismink
Anthonie Z M
AZ
Geldof
Han
H
Bode
Willem A
WA
Krishnadath
Kausilia K
KK
Bergman
Jacques J G H M
JJ
van Vliet
Arnoud H M
AH
Siersema
Peter D
PD
Kusters
Johannes G
JG
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D000483:Alleles; D001471:Barrett Esophagus / Q000235:genetics; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2 / Q000235:genetics*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics*; D004942:Esophagitis, Peptic / Q000235:genetics; D004945:Esophagoscopy; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors
D051546:Cyclooxygenase 2