Analysis of the cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) gene polymorphisms in colorectal cancer

• Grant number: 11/23181-5
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2012 - August 31, 2013
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ulysses Ribeiro Júnior
• Grantee: Ulysses Ribeiro Júnior
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Polymorphic genes' study may aid in the detection of people at higher risk of developing cancer, characterization of differentiated outcome, distinctive response to chemotherapy or radiotherapy and prognosis. Cyclooxygenase-2 (COX-2) is induced in response to growth factor and cytokines, and it is expressed in inflammatory diseases, precancerous lesions and colorectal tumors. On the other hand, the vascular endothelial growth factor (VEGF) is a soluble molecule that mediates potential mitogen for vascular endothelial cells isolated from small and large vessels, actively participating in tumor neoangiogenesis. This study aims to investigate the frequency of COX-2 polymorphisms (1195A> G,-765G> C and 8473T> C) and VEGF (-2578C> A,-634G> C,-460C> T and 936C > T) in patients who have undergone surgical treatment for colorectal cancer. Two hundred and thirty colorectal cancer resected patients admitted at the Hospital das Clinicas of University of São Paulo School of Medicine form the study group. One hundred and ninety-four patients operated for benign disease at the same institution, matched for age and sex, and no individual or familial 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 VEGF, through the TaqMan ® SNP Genotyping Assay. For the analysis of tissue expression will be used tissue microarray (TMA) from colorectal tumors blocks fixed in formaldehyde and paraffin. Immunohistochemical analysis will be performed using the immunoperoxidase technique with monoclonal antibodies against COX-2 and VEGF. The results of the polymorphisms will be associated to epidemiological, clinicopathological and immunohistochemical features of the patients. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TATIANA PEREIRA TOMITAO, MICHELE; CARLOS NAHAS, SERGIO; SALDANHA KUBRUSLY, MARCIA; KATSUE FURUYA, TATIANE; AUGUSTO DINIZ, MARCIO; KAZUE NAGAHASHI MARIE, SUELY; VAZ SAFATLE-RIBEIRO, ADRIANA; ELUF-NETO, JOSE; CECCONELLO, IVAN; RIBEIRO, JR., ULYSSES. Cyclooxygenase-2 gene polymorphisms and susceptibility to colorectal cancer in a Brazilian population. JOURNAL OF GASTROINTESTINAL ONCOLOGY, v. 8, n. 4, p. 629-635, AUG 2017. (11/23181-5)