PTGS2 (COX-2) −765 G > C functional promoter polymorphism and its association with risk and lymph node metastasis in nasopharyngeal carcinoma
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Cyclooxygenase-2 (Cox-2) is a key enzyme in the conversion of arachidonic acid to prostaglandins that has been shown to have a particular importance in the progression of several malignancies including nasopharyngeal carcinoma (NPC). In the current report, we designed a case-controlled study to evaluate the susceptibility and prognostic implications of the functional −765 G > C genetic variation in NPC. A PCR and restriction fragment length polymorphism analysis was used to determine the polymorphism in a Tunisian population of patients with NPC (n = 180) and in healthy control subjects (n = 169). A higher risk for NPC was observed for carriers of COX-2 −765 C allele (OR = 1.76; P = 0.01). This association remains significant after adjustments for age and sex (OR = 1.89; P = 0.008). Regarding prognostic indicators, a significant association was found between −765 C allele carriers and the presence of lymph node metastasis (OR = 2.28; P = 0.01), as well as, with tumor stage (OR = 2.73; P = 0.03). This is the first report on the studies of COX-2 SNPs in NPC and our data suggest that this genetic variant may play a role in mediating susceptibility to NPC, as well as, in neoplastic progression, a finding which further supports the involvement of COX-2 in NPC etiology.
KeywordsCOX-2 Nasopharyngeal carcinoma Polymorphism Prognosis Susceptibility
Single nucleotide polymorphism
This work was supported by le Ministère de la Recherche Scientifique de Technologie et du développement des Compétences, le Ministère de l’Enseignement Supérieur, le Ministère de la Santé Publique de la République Tunisienne. We gratefully acknowledge the technical assistance of S. Gabbouj. We thank the staff of the Departments of Radiation Oncology and Medical Oncology of CHU F. Hached, Sousse, for providing samples and clinical information.
- 14.Humar B, Giovanoli O, Wolf A, Attenhofer M, Bendik I, Meier R, Muller H, Dobbie Z (2000) Germline alterations in the cyclooxygenase-2 gene are not associated with the development of extracolonic manifestations in a large Swiss familial adenomatous polyposis kindred. Int J Cancer 87:812–817PubMedCrossRefGoogle Scholar
- 19.Zhang X, Miao X, Tan W, Baitang N, Liu Z, Hong Y, Song W, Guo Y, Zhang X, Shen Y, Qiang B, Kadlubar FF, Lin D (2005) Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. Gastroenterol 129:565–576Google Scholar
- 21.Tan W, Wu J, Zhang X, Guo Y, Liu J, Sun T, Zhang B, Zhao D, Yang M, Yu D, Lin D (2007) Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer. Carcinogenesis 26(6):1197–1201CrossRefGoogle Scholar
- 25.Gao J, Ke O, Ma HX, Wang Y, Zhou Y, Hu ZB, Zhai XJ, Wang XC, Qing JW, Chen WS, Jin GF, Liu JY, Tan YF, Wang XR, Shen HB (2007) Functional polymorphisms in the cyclooxygenase 2 (COX-2) gene and risk of breast cancer in a Chinese population. J Toxicol Environ Health A 70(11):908–915PubMedCrossRefGoogle Scholar
- 26.Vogel U, Christensen J, Wallin H, Friis S, Nexø BA, Tjønneland A (2007) Polymorphisms in COX-2, NSAID use and risk of basal cell carcinoma in a prospective study of Danes. Mut Res 617:138–146Google Scholar
- 34.Liu Y, Zhao S, Liu G, Li Z, Sun Z, Jiang W (2007) The value of cyclooxygenase-2 to predict the effect of radiotherapy in nasopharyngeal carcinoma. Lin Chung Er Bi Yan Hon Tou Jing Wai Ke Za Zhi 21(5):199–202Google Scholar
- 35.Chan CML, Ma BBY, Hui EP, Wong SCC, Mo FKF, Leung SF, Kam MKM, Chan ATC (2006) Cyclooxygenase-2 expression in advanced nasopharyngeal carcinoma- a prognostic evaluation and correlation with hypoxia inducible factor 1α and vascular endothelial growth factor. Oral Oncol 43(4):373–378PubMedCrossRefGoogle Scholar
- 43.Mamoghli T, Douik H, Ghanem A, Ben Chaabene A, Harzallah L, Baatout H, Guemira F (2007) Polymorphisme cox2 et risque de cancer du nasopharynx en Tunisie. Bull Cancer 93(6):562Google Scholar