Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma.
OBJECTIVE
To determine whether -1195 A-->G and/or -765 G-->C polymorphisms in Cyclooxygenase-2 (COX-2) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population.


METHODS
Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated.


RESULTS
The distribution of the -1195 A-->G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma (OR = 3.85, 95% CI: 1.45-10.3) compared with the -1195 AA genotype as a reference. The -765 G-->C genotype distribution was not different between the two groups. The GG/GG haplotype was present more often in esophageal adenocarcinoma patients than in controls (OR = 3.45, 95% CI: 1.24-9.58; with AG/AG as a reference). The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance.


CONCLUSIONS
Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.
Kristinsson
Jón O
JO
Department of Gastroenterology, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
van Westerveld
Paul
P
te Morsche
Rene H M
RH
Roelofs
Hennie M J
HM
Wobbes
T
T
Witteman
Ben J M
BJ
Tan
Adriaan C I T L
AC
van Oijen
Martijn G H
MG
Jansen
Jan B M J
JB
Peters
Wilbert H M
WH
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human