COX-2 polymorphisms in patients with familial adenomatous polyposis.
Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of biologic processes such as inflammation, cell proliferation, and angiogenesis. COX-2 has been found overexpressed in (pre)malignant tissues and may be relevant to cancer development. We investigated whether functional genetic polymorphisms in COX-2 may have a risk-modifying effect on duodenal adenomatosis in patients with familial adenomatous polyposis (FAP). Blood from 85 patients with FAP and 218 age- and sex-matched healthy subjects was investigated for the presence of two functional promoter region polymorphisms (-1195G-->A and -765G-->C) in COX-2. Logistic regression analysis revealed an overrepresentation of the -1195GG genotype compared to the -1195AA genotype in patients with FAP (odds ratio = 2.81; 95% CI = 1.00-7.91, p = 0.042). No associations between single COX-2 polymorphisms or COX-2 haplotype were found when patients were evaluated according to their Spigelman stage. The predicted low COX-2 expression genotype -1195GG was found overrepresented in the patients with FAP. The COX-2 genotypes showed no association with the severity of duodenal adenomatosis.
Peters
Wilbert H M
WH
Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. w.peters@mdl.umcn.nl
te Morsche
Rene H M
RH
Roelofs
Hennie M J
HM
Mathus-Vliegen
Elisabeth M H
EM
Berkhout
Marloes
M
Nagengast
Fokko M
FM
D011125:Adenomatous Polyposis Coli / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
D051546:Cyclooxygenase 2