Journal of Molecular Biology Research; Vol.9,No. 1; 2019 ISSN 1925-430X E-ISSN 1925-4318 Published by Canadian Center of Science and Education 133 The Association between Functional Polymorphisms of COX-2 and Serum PGE2 Level in ESCC Patients in North of Iran Maryam Sadegh Sheshpoli 1, 3 , Safoura Khajeniazie 2 , Masoud Khoshnia 3 , Nasser Behnampour 4 , Mohsen Saeedi 5 & Abdolvahab Moradi 3 1 School of New Technologies, Golestan University of Medical Sciences, Gorgan, Iran 2 Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran 3 Golestan Research Center of Gastroenterology and Hepatology, Gorgan, Iran 4 Health Management and Social Development Research Center, Gorgan, Iran 5 Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran Correspondence author: Abdolvahab Moradi, Golestan Research Center of Gastroenterology and Hepatology. Golestan University of Medical Sciences, Gorgan, 4934174515, Iran. E-mail: abmoradi@yahoo.com Received: May 22, 2019 Accepted: September 29, 2019 Online Published: October 23, 2019 doi:10.5539/jmbr.v9n1p133 URL: https://doi.org/10.5539/jmbr.v9n1p133 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. Keywords: Cyclooxygenase-2, Prostaglandin-E2, Esophageal cancer 1. Introduction Cancer is one of the most important health issues and one of the most important reasons of death worldwide (Bab et al., 2018). It is caused by the uncontrolled generation of the abnormal cells (Alkhatib et al., 2017) that results in malignant growth, and eventually severe morbidity and mortality (Alshammari, 2018). Despite steps taken to improve knowledge regarding cancer, the burden of cancer is still rising at a great rate worldwide (Sundus at al., 2018; Abdel-Sattar et al., 2018). Esophageal cancer is a major global health concern and the sixth most common cause of cancer death. (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. It has been defined as "the succession of changes which occurs in a living tissue when it is injured provided that the injury is not of such a degree as to at once destroy its structure and vitality" or "the reaction to injury of the living microcirculation and related tissues” (Hemashree & Thangavelu, 2018). COX-2 enzyme is one of the most important factors involved in inflammation.(Greenhough,Smartt,Moore, Roberts,Williams & Cancer, 2009)This