Abstract 4845: VEGF-A and Cox-2 gene polymorphisms and susceptibility to colorectal cancer in Brazilian population.

Abstract

Background: Brazilian population displays very high levels of genomic diversity due to the multi-ethnicity, which have important clinical/genomic implications. The vascular endothelial growth factor-A (VEGF-A) and Cyclooxygenase-2 (Cox-2) polymorphisms have been implicated in colorectal cancer (CRC) risk, however, the results on the association between polymorphisms and cancer risk are conflicting. VEGF and Cox-2 polymorphisms might modify the levels of mRNA and protein expression and may have a considerable influence on disease phenotype. Aim: We carried out a case-control study to evaluate whether polymorphisms of VEGF-A and Cox-2 genes modulate the risk of developing CRC. We also aimed to investigate possible interactions between these genetic variations and environmental factors in CRC. Methods: We evaluated VEGF-A and Cox-2 genotypes obtained from a series of 230 CRC patients and 194 controls from the Hospital-based Brazilian population. DNA was isolated from leukocyte using extraction and purification kit PureLink, followed by amplification by polymerase chain reaction (PCR). Real-time analysis was used for genotyping of polymorphisms of VEGF-A and Cox-2, through the TaqMan ® SNP Genotyping Assay. There was no difference between the cases and controls regarding gender, age, ethnicity, and no individual or familial history of cancer was found in control cases. Results: We determined frequencies of four VEGF-A biallelic polymorphisms (-2578C>A, -460T>C, -634G>C, +936C>T), with twelve genotypes; and three Cox-2 polymorphisms (-1195A>G, -765G>C, 8437T>C,) with nine genotypes. The genotypes frequencies were similar in both case and control groups, and there was, therefore, no association between these genotypes and CRC risk. A high frequency of the wild genotype Cox-2 -765GG and 8437TT and polymorphic genotype Cox-2 -1195GG and VEGF-A -634CC was found in an Asiatic (mostly Japanese) population. Moreover, VEGF-A -2578C>A, and -460T>C were associated to familial history of cancer in the cases series. Tobacco consumption was marginally associated to Cox-2 -1195A>G genotype. Conclusion: VEGF-A and Cox-2 gene polymorphisms are not associated with an increased risk of CRC in a Brazilian population. We could demonstrate the genotype differences among ethnicity, and the association of these polymorphisms with some risk-factors for CRC. Citation Format: Michele T. P. Tomitão, Márcia S. Kubrusly, Guilherme C. Cotti, Evelise P. Zaidan, Adriana V. Safatle-Ribeiro, Suely K. N. Marie, Ivan Cecconello, Sergio C. Nahas, Ulysses Ribeiro. VEGF-A and Cox-2 gene polymorphisms and susceptibility to colorectal cancer in Brazilian population. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4845. doi:10.1158/1538-7445.AM2013-4845