Abstract
Cyclooxygenases are key enzymes in conversion of arachidonic acid into prostaglandin H2. Cyclooxygenase-2 (COX-2) increases prostaglandins in neoplastic tissue. COX-2 has important roles in cell proliferation cancers, angiogenesis, and alzheimer. COX-2 is up-regulated in several types of cancer, and it is hypothesized that COX-2 expression may be genetically influenced. Our main objective was to evaluated the association of polymorphism COX-2 with risk of breast cancer in khouzestan province, and the second objective of the study was to evaluate the association with biochemistry parameters. This study consisting of 150 patients with breast cancer and 120 normal DNA was extracted from the white blood cells. Polymorphism cox2 gene was detected by polymerase chain reaction according to the standard methods. The profile lipids and estrogen were measured in two groups by standard methods. Chi square analysis showed that there was no association between breast cancer risk and COX-2 −765G>C genotype and alleles. Also, no association were observed between −765G>C polymorphism and biochemistry parameters. A multiple logistic regression model with cox2 genotypes and LDL and HDL as covariates revealed that there is no significant association between cox2 genotypes and risk of breast cancer, but higher values of LDL and HDL significantly increase risk of breast cancer.
Similar content being viewed by others
References
Needleman P, Turk J, Jakschik BA et al (1986) Arachidonic acid metabolism. Annu Rev Biochem 55:69–102
Smith WL, Garavito RM, DeWitt DL (1996) Prostaglandin endoperoxidesynthases(cyclooxygenases)-1 and -2. J Biol Chem 271:33157–33160
Zha S, Yegnasubramanian ZS, Nelson WG et al (2004) Cyclooxygenases in cancer: progress and perspective. Cancer Lett 205:1–20
Wang JM, Ko CY, Chen LC et al (2006) Functional role of NF-IL6beta and its sumoylation and acetylation role of NF-IL6beta and its sumoylation and acetylation modifications in promoter activation of cyclooxygenase-2 gene. Nucleic Acids Res 34:217–231
Gallicchio L, McSorley MA, Newschaffer CJ et al (2006) Nonsteroidal anti inflammatory drugs, cyclooxygenase polymorphisms, and the risk of developing breast carcinoma among women with benign breast disease. Cancer 106:1443–1452
Pereira C, Sousa H, Ferreira P et al (2006) −765G>C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia. World J Gastroenterol 12:5473–5478
Shahedi K, Lindstrom S, Zheng SL, Wiklundand et al (2006) Genetic variation in the COX-2 gene and the association with prostate cancer risk. Int J Cancer 119:668–672
Ali IU, Luke BT, Dean M et al (2005) Allellic variants in regulatory regions of cyclooxygenase-2: association with advanced colorectal adenoma. Br J Cancer 93:953–959
How LR, Subbaramaiah K, Brown AM et al (2001) Cyclooxygenase-2 a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 8:97–114
Saxena A, Prasad KN, Ghoshal UC et al (2008) Polymorphism of −765G>C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection: a study from northern India. World J Gastroenterol 14:1498–1503
Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16(3):1215
Tan W, Wu J, Zhang X et al (2007) Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer. Carcinogenesis 28:1197–1201
Dannenberg AJ, Subbaramaiah K (2003) Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell 4:431–436
Dannenberg AJ, Altorki NK, Boyle JO et al (2001) Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol 2:544–551
Dannenberg AJ, Howe LR (2003) The role of COX-2 in breast and cervical cancer. Prog Exp Tumor Res 37:90–106
Langsenlehner U, Yazdani-Biuki B, Eder T et al (2006) The cyclooxygenase-2 (PTGS2) 8473T > C polymorphism is associated with breast cancer risk. Clin Cancer Res 12:1392–1394
Zhang X, Miao X, Tan W et al (2005) Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. Gastroenterology 129:565–576
Campa D, Zienolddiny S, Zienolddiny S, Maggini V et al (2004) Association of a common polymorphism in the cyclooxygenase-2 gene with risk of non-small cell lung cancer. Carcinogenesis 25:229–235
Li F, Ren GS, Li HY et al (2009) A novel single nucleotide polymorphism of the cyclooxygenase-2 gene associated with breast cancer. Clin Oncol (R Coll Radiol) 4:302–305
Ulrich CM, Whitton J, Yu JH, Sibert J et al (2005) PTGS2 (COX-2) −765G>C promoter variant reduces risk of colorectal adenoma among nonusers of nonsteroidal anti-inflammatory drugs. Cancer Epidemiol Biomarkers Prev 14(3):616–619
Diogo NP, Juliana SF, Laura MA et al (2010) Polymorphisms in regulatory regions of cyclooxygenase-2 gene and breast cancer risk in Brazilians: a case-control study. BMC Cancer 10:613
Williams CS, Mann M, DuBois RN (1999) The role of cyclooxygenasesin inflammation, cancer, and development. Oncogene 18:7908–7916
Zhu W, Wei BB, Shan X et al (2010) −765G>C and 8473T > C polymorphisms of COX-2 and cancer risk: a meta-analysis based on 33 case-control studies. Mol Biol Rep 37(1):277–288
Xing L-L, Wang Z-N, Jiang L et al (2008) Cyclooxygenase-2 polymorphism and colorectal cancer: −765G>c variant modifies risk associated with smoking and body mass index. World J Gastroenterol 14(11):1785–1789
Soslow RA, Dannenberg AJ, Rush D et al (2000) Cyclooxigenase is expressed in human pulmonary, colonic and mammary tumours. Cancer 89:2637–2645
Singh-Ranger G, Mokbel K (2002) The role cyclooxygenase-2 (cox2) in breast cancer, and implication of cox2 inhibition. Eur J Surg Oncol 28:729–737
Montali A, Barillà F, Tanzilli G et al (2010) Functional rs20417 SNP (−765G>C) of cyclooxygenase-2 gene does not predict the risk of recurrence of ischemic events in coronary patients: results of a 7-year prospective study. Cardiol J 115(3):236–242
Kohsaka S, Volcik KA, Folsom AR et al (2008) Increased risk of incident stroke associated with the cyclooxygenase-2 (COX-2) G-765C polymorphism in African–Americans: the atherosclerosis risk in communities study. Atheroscler J 196(2):926–930
Lee CR, North KE, Bray MS, Couper DJ et al (2008) Cyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study. Clin Pharmacol Ther 83(1):52–60
McKeown N (1999) Antioxidants and breast cancer. Nutr Rev 57:321–324
Wesseling C, Antich D, Hogstedt C et al (1999) Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure. Int J Epidemiol 28:365–374
Ulrich CM, Whitton J, Yu JH et al (2005) PTGS2 (COX-2) −765G>C promoter variant reduces risk of colorectal adenoma among nonusers of nonsteroidal anti-inflammatory drugs. Cancer Epidemiol Biomarkers Prev 14:616–619
Acknowledgments
The authors thank all the subjects for participating. This study was supported by the Department of Biochemistry, Faculty of Medicine, Ahvaz Jondishapour University of Medical sciences, Ahvaz, Iran.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Ahmadi, B., Nikzamir, A., Ghafari, S.M. et al. Lack of association between cyclooxygenase 2−765G/C gene polymorphism and breast cancer risk in Ahvaz, west-south Iran. Mol Biol Rep 41, 997–1001 (2014). https://doi.org/10.1007/s11033-013-2944-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-013-2944-1