To assess COX-2 expression, in relation to adenoma recurrence and the protective effect of aspirin, in a large series of colorectal adenomas, recruited from a double-blind randomised controlled trial comparing recurrences after low-dose aspirin or placebo.
Treatment of colorectal adenomas with selective cyclooxygenase-2 inhibitors can contribute to the chemoprevention of colorectal cancer (CRC), but the molecular background of their effect is not fully understood.
Taken together, our results suggest that overexpression of mPGES in addition to COX-2 contributes to increased amounts of PGE(2) in colorectal adenomas and cancer.
A protective effect on colorectal adenomas was found for the CT genotype of SNP H477H in PPARgamma and the GC genotype of SNP V102V in COX-2 (OR 0.63, 95% CI 0.45-0.89 and OR 0.65, 95% CI 0.46-0.92, respectively) compared with the homozygous major genotypes.
Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma.
Three of those (COL1A2, SFRP2, SOCS3) showed hypermethylation and THBS2 showed hypomethylation both in AD and in CRC samples compared to NAT, while BCL2, PRIMA1 and PTGDR showed hypermethylation only in the CRC group. miR-21 was found to be significantly (p < 0.01) upregulated in adenoma and tumour samples compared to the healthy colonic tissue controls and could explain the altered expression of genes for which DNA methylation changes do not appear to play role (e.g.BCL2, MAL, PTGS2).
However, subset analysis suggested that this lack of response to celecoxib was confined to those patients with 15-PGDH intact tumors who were also using cardioprotective aspirin.<b>Conclusions:</b> The expression of Cox-2 and 15-PGDH in pre-treatment adenomas provides predictive information in patients treated with celecoxib for prevention of colorectal adenomas.<b>Impact:</b> The results of this study show that Cox-2 and 15-PGDH are characteristics of colorectal adenomas that may be used to predict nonsteroidal anti-inflammatory drug chemoprevention efficacy.
The cyclooxygenase (COX) pathway is important in colorectal carcinogenesis with the majority of cancers overexpressing COX-2; however, the role of COX-2 in the development of colorectal adenomas is less well defined.
Homozygote carriers of variant alleles for the PTGS1 50C>T, PTGS2 -765G>C and IL-10 -592C>A polymorphisms did not have a significantly altered risk of CRA recurrence (relative risk [RR]=0.91; 95% confidence interval [CI]: 0.14-6.07, RR=1.32; 95% CI: 0.66-2.62 and RR=1.24; 95% CI: 0.74-2.07, respectively).
High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer.
We have previously described an association between colorectal adenomas and SNP V102V in PTGS2 and have now confirmed this association for colorectal adenocarcinomas.
An increase of COX-2-positive cells in adenoma was observed in 11 (37.9%) lesions, 10 (90.9%) of which had a K-ras gene mutation, suggesting a significant correlation between COX-2 expression and K-ras gene mutation in colorectal adenomas.
To investigate expression of HuR in the colorectal adenoma-carcinoma sequence, we examined expression of HuR in colorectal mucosa of patients with familial adenomatous polyposis (FAP) and sporadic colorectal cancer with correlation to COX-2 expression.
Treatments with COX-2-specific NSAIDs have been shown to reduce polyp size and polyp number in FAP patients with a predisposition to colorectal adenoma and cancer.
This study investigated the relation of COX-2 polymorphisms (-1195G>A, -765G>C and 8160A>G) to colorectal adenomas in a case-control study of male officials in the Self Defense Forces (SDF).
We investigated the association of colorectal adenoma with 19 single nucleotide polymorphisms in a range of important proinflammatory (IL1B, IL6, IL8, TNF, and LTA) and anti-inflammatory (IL4, IL10, and IL13) cytokines and other inflammation-related genes (PTGS2 and PPARG) in a case-control study of risk factors for colorectal polyps in which all participants (ages 18-74 years) had undergone colonoscopy or sigmoidoscopy.
Paracrine cyclooxygenase-2 activity by macrophages drives colorectal adenoma progression in the Apc <sup>Min/+</sup> mouse model of intestinal tumorigenesis.