The Association between Functional Polymorphisms of COX-2 and Serum PGE2 Level in ESCC Patients in North of Iran

Abstract

Background: Esophageal cancer is recognized as one of the most fatal diseases around the world. Many factors are involved in the development of esophageal cancer, including genetic factors and inflammation. Cyclooxygenase-2 (COX-2) and its downstream signaling are the most important proinflammatory factors contributing to cancer. The present study aimed to evaluate the relationship between the polymorphisms and expression of COX-2 and prostaglandin-E2 (PGE2) level in patients with esophageal squamous cell carcinoma (ESCC) in Golestan Province (Iran), situated on the “esophageal cancer belt”. Methods: In this case-control study, blood and biopsy samples were obtained from ESCC patients and healthy controls. The COX-2 polymorphisms for -1195, -1290, -765, and +8473 SNPs were assayed using PCR-RFLP assay, while the level of PGE2 was measured using an ELISA kit. In addition, real-time PCR assay and immunohistochemistry (IHC) were performed to assay mRNA and protein expression of COX-2, respectively. Results: An association was found between 8473TC genotype and risk of ESCC (OR= 5.417, P= 0.036). In addition, mRNA and protein expression of COX-2 in ESCC patients was higher than the controls (P=0.001 and P=0.048, respectively). Based on the findings, the level of PGE-2 was significantly higher in ESCC patients, compared to the controls (P= 0.045). However, ROC curve analysis revealed PGE2 is a weak biomarker for diagnosis of ESCC. There was a significant relationship between the level of PGE2 and 8473CC, 8473TC, -765CC, and -1290AA genotypes (P= 0.028, P= 0.022, P= 0.024, and P= 0.011, respectively). Conclusion: Based on our results, functional polymorphisms of COX-2 (8473CC, 8473TC, - 765CC, and -1290AA) increase PGE2 level and carriers of these polymorphisms might be more susceptible to ESCC.