Our results suggested that the COX-2 promoter polymorphisms were associated with increased risk of GC, especially interacting with H. pylori infection.
These findings suggest that induction of 15-LOX-1-mediated down-regulation of a PPAR-gamma and COX-2 pathway by honokiol may be a promising therapeutic strategy for gastric cancer.
The -765C, -1195A, -1290G, *2430T alleles and *429TT genotype of COX-2 polymorphisms were determined a significant association with susceptibility to GC.
In addition, our findings also suggest that reduction of COX-2 using nonsteroidal anti-inflammatory drugs in gastric cancer chemoprevention may only be relevant for older patients.
The over-expression of COX-2 (Cyclooxygenase 2) protein has been reported to play a key role in the incidence and development of Helicobacter pylori-associated gastric cancer.
Both forced COX-2 overexpression and high-salt intake significantly increased the frequency of gastric cancer development in mice as compared with WT littermates treated with MNU alone.
Cyclo-oxygenase (COX) profile predicts prognosis of gastric cancer; COX-2 positive tumors are more often aggressive, and COX-2 suppression is protective against gastric cancer.
Previously we have found that early-onset gastric cancer has a unique COX-2 low-expressing phenotype that differs significantly from that of the frequent overexpression seen in conventional gastric cancers.
COX-2 may play an important role in the development of gastric cancer, and the over-expression of COX-2 protein may be a high risk factor for liver metastasis.
From CSG to GA, IM, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency, whereas COX-1 expression did not change significantly in the gastric mucosa.
These biological factors are often derived from the genetic process, which is thought to represent a crucial step to gastric cancer (DNA copy number changes, microsatellite instability, thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2, COX-2, matrix metalloproteinases, VEGFR and EGFR).
Five different classes of methylation behaviors were found: (a). genes methylated in GC only (GSTP1 and RASSF1A), (b). genes showing low methylation frequency (<12%) in CG, IM, and gastric adenoma (GA) but significantly higher methylation frequency in GC (COX-2, hMLH1, p16), (c). a gene with low and similar methylation frequency (8.8-21.3%) in four-step lesions (MGMT), (d). genes with high and similar methylation frequency (53-85%) in four-step lesions (APC and E-cadherin), and (e). genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP-3).
Five different classes of methylation behaviors were found: (1) genes methylated in GC only (GSTP1 and RASSF1A); (2) genes showing low methylation frequency (<12%) in CG, IM, and GA, but significantly higher methylation frequency in GC (COX-2, hMLH1, and p16); (3) a gene with low and similar methylation frequency (8.8-21.3%) in four-step lesions (MGMT); (4) genes with high and similar methylation frequency (53-85%) in four-step lesions (APC and E-cadherin); and (5) genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP3).
Infection with H. pylori, especially that expressing CagA-positivity, is primum movens in developing GC and MALT-lymphoma and the upregulation of growth factors, particularly of gastrin, and COX-2 and dysregulation of the Bax/Bcl-2 system seem to contribute to gastric cancerogenesis.