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.
Highlights
Cancer is one of the most important health issues and one of the most important reasons of death worldwide (Bab et al, 2018)
Upadhyay R et al (2009) showed that −1195G>A, −1290A>G, and 3ʹ-UTR 8473T>C polymorphisms had no significant association with esophageal squamous cell carcinoma (ESCC), whereas 765GC and CC polymorphisms conferred ESCC susceptibility in an Indian population. (Upadhyay et al, 2009) In the present study, individuals carrying 765GC genotypes were found to be more susceptible to ESCC, which is in line with the results reported by Upadhyay R and colleagues
We found that −1195 G>A polymorphism was not associated with the serum concentration of PGE2; PGE2 level in patients with 1290 AAgenotype was significantly different from healthy subjects with the same genotype (P= 0.011)
Summary
Cancer is one of the most important health issues and one of the most important reasons of death worldwide (Bab et al, 2018). (Smyth et al, 2017) There are two subtypes of esophagus cancer (EC) with respect to cellular morphology, including squamous cell carcinoma (SCC) and adenocarcinoma.(Zhi, Zhang, Hu, Lu, & Wang, 2003) Generally, inflammation is a response of the immune system to infection, injury, and 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”. 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
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