Association Between Single Nucleotide Polymorphisms in the Cyclooxygenase-2, Tumor Necrosis Factor-a, and Vascular Endothelial Growth Factor-A Genes, and Susceptibility to Hepatocellular Carcinoma

Abstract

Cyclooxygenase-2 (COX-2), vascular endothelial growth factor-A (VEGF-A), and tumor necrosis factor-a (TNF-a) are mediators of inflammation and angiogenesis; all of them are produced in liver cirrhosis (LC) and in hepatocellular carcinoma (HCC). It was proposed that there is an association between single nucleotide polymorphisms (SNPs) and HCC. These allelic variants influence the transcriptional activity of these genes, and therefore the proteins levels. The VEGF-A pathway is a potential therapeutic target in HCC, and several antiangiogenic agents have entered clinical trials in HCC. We evaluated the frequency of SNPs of COX-2, TNF-a, and VEGF-A genes in patients with HCC versus LC patients and a control group. The aim of this article was to verify the correlation between the allelic variations and the risk of developing HCC. The study included 96 HCC, 79 LC patients, and 162 healthy subjects. The evaluation of SNPs was performed by the restriction fragment length polymorphism (RFLPPCR) method. The SNPs analyzed were: 1195G>A of the COX-2 gene, 308G>A of the TNF-a gene, and +936C>T of the VEGF-A gene. Chi-square and Fisher exact tests were used for statistical analysis. Our results confirm that carriers with the C allele in the VEGF-A gene are more frequent in HCC versus LC ( p¼0.039), suggesting that this SNP may predispose to the development of HCC.