Analysis of the cyclooxygenase-2 (COX-2) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in esophageal cancer

• Grant number: 12/17920-2
• Support type: Regular Research Grants
• Duration: December 01, 2012 - November 30, 2013
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal researcher: Ulysses Ribeiro Júnior
• Grantee: Ulysses Ribeiro Júnior
• Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Studies of genetic polymorphisms may obtain a description of the risk factors, progression, prognosis and susceptibility of the cancer. Cyclooxygenase-2 (COX-2) is induced in response to growth factor and cytokines, expressed in inflammatory diseases, premalignant and esophageal tumors. The product of folate metabolism by the enzyme methylenetetrahydrofolate reductase acts in DNA synthesis, alteration or inhibition of this enzyme increases the susceptibility to mutations, damage and altered DNA methylation, gene expression of transforming the tumor suppressor and proto- ontogenesis, potential risk factors for esophageal cancer. This research aims to investigate the frequency of COX-2 polymorphisms (-1195A> G,-765G> C, 8473T> C and-1759G> A), and MTHFR (677C> T and 1298C> A) in patients with esophageal cancer. One hundred and fifty patients with a diagnosis of adenocarcinoma or squamous cell carcinoma of the esophagus histologically confirmed, Hospital das Clinicas of University of São Paulo School of Medicine form the study group. All patients underwent surgical resection between June 2001 and January 2008. The same number of patients operated for benign disease at the Hospital das Clinicas of University of São Paulo School of Medicine, matched for age and sex, no individual or family history of cancer will be the control group. Genomic DNA will be isolated from leukocyte using extraction and purification kit PureLink "Genomic DNA Mini Kit. The identification technique based on the use of probes labeled with fluorophores, followed by amplification by polymerase chain reaction (PCR) and real-time analysis will be used for genotyping of polymorphisms of COX-2 and MTHFR, through the TaqMan ® SNP Genotyping Assay. For the analysis of tissue expression will be used tissue microarray (TMA) from esophageal tumors blocks fixed in formaldehyde and paraffin. Immunohistochemical analysis will be performed using the immunoperoxidase technique with monoclonal antibodies against COX-2. The results of the polymorphisms will be associated to epidemiological, clinicopathological and immunohistochemical features of the patients. (AU)