Polymorphisms in the regulatory regions of the COX-2 gene may influence function and/or expression and contribute to interindividual variability in susceptibility to cancer.
To investigate whether the COX-2 -765 G>C promoter polymorphism (known to lead to a reduction of COX-2 promoter activity in the colon) may explain this difference in expression, we carried out single-nucleotide polymorphism (SNP) analysis of 241 gastric cancers, including early-onset gastric cancer, conventional gastric cancers and gastric stump cancers, as well as in 100 control patients, using real-time PCR and sequence analysis, and correlated these findings with COX-2 expression using immunohistochemistry.
The effect of three potentially functional polymorphisms (-765G>C, -1195G>A, and 8473T>C) in the COX-2 gene on cancer risk provided evidence that the COX-2-1195G>A polymorphism was significantly associated with increased risk of digestive system cancers, especially among Asian populations.
Single-nucleotide polymorphisms (-765G/C: rs20417, -1195A/G: rs689466, and -1290A/G: rs689465) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer.
To determine if common known polymorphisms in the regulatory region of the COX-2 gene (PTGS2) can be associated with nonmelanoma skin cancer (NMSC) predisposition after organ transplantation, to evaluate if cancer risks are associated with specific COX-2 gene (PTGS2) haplotypes containing these polymorphisms, and to identify possible new genetic polymorphisms in the proximal 5' or 3' regulatory regions of the gene associated with disease.
Our findings indicate that the COX-2T8473C polymorphism may contribute to NSCLC cancer susceptibility in the Kashmiri population, while our expression analysis revealed a significant increase of COX-2 in tumor tissues as compared to their adjacent normal tissues, suggesting that it could become an important therapeutic marker in NSCLC in the future.
Functional coding region polymorphisms -1195A>G (rs689466), -765G>C (rs20417), and +8473T>C (rs5275) in the COX-2 gene have recently been shown to be associated with several human cancers but their association with HCC has yet to be investigated.
We used odds ratios (ORs) with confidence intervals (CIs) of 95% to assess the strength of the association between the COX-2-765G>C polymorphism and cancer risk in a random-effect model.
We investigated associations between PTGS2 polymorphisms and prostate cancer risk among 2321 prostate cancer cases and 2560 controls in two large case-control studies nested within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Cancer Prevention Study II Nutrition Cohort.
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been reported to exert chemopreventive and antitumor effects on colon cancer, one of the most common solid epithelial malignancy worldwide.
Moreover, these findings strengthen the rationale for determining whether inhibitors of COX-2 or EGFR tyrosine kinase activity can reduce the risk of tobacco smoke-related malignancies of the aerodigestive tract.
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.
Resveratrol is a stilbenoid phytoalexin which binds to a specific site on the cell surface integrin αvβ3 to trigger cancer cell death via nuclear translocation of COX-2.
For PTGS2rs5275 and rs20417, there were no significant differences between the gene polymorphism and NSAID use on cancer risk among the 8 and 7 studies, respectively.
The COX-2 genotypes for 7 single-nucleotide polymorphisms (rs2745557, rs5277, rs2066826, rs4648261, rs4648262, rs2206593, and rs5275) were determined in 162 pancreatic cancer patients and 170 control subjects without cancer who were matched for age and sex.
For the two latter, NSAID use was only associated with a lower cancer risk among homozygous wild type allele carriers. p for interaction was 3 x 10(-6) for COX-2A-1195G and 9 x 10(-5) for PPARgamma2 Pro(12)Ala.
Several clinical studies indicated that the daily use of aspirin or acetylsalicylic acid reduces the cancer risk via cyclooxygenases (Cox-1 and Cox-2) inhibition.