Role of VEGF-C gene polymorphisms in susceptibility to hepatocellular carcinoma and its pathological development

Background: Vascular endothelial growth factor C (VEGF-C), an angiogenic/lymphangiogenic factor with high expression levels in tumor tissues, plays important roles in the development of several malignancies including hepatocellular carcinoma (HCC). The purpose of this study was to examine whether VEGF-C gene polymorphisms are associated with susceptibility to HCC and its clinicopathological development. Methods: Genetic polymorphisms of VEGF-C of 135 patients with HCC and 520 noncancer controls were analyzed by a real-time polymerase chain reaction (PCR). Results: We found that a significantly (P = 0.021) higher risk for HCC was shown in individuals with the VEGF-C rs1485766 A/A genotype compared to those with wild-type homozygotes; a high frequency of an advanced stage and a low frequency of being positive for cirrhosis were respectively shown in HCC patients with the VEGF-C rs7664413 CT/TT and rs3775194 GC/CC genotypes. Moreover, we found that the GGACA, GACTG, CGATG, and GGCTG haplotypes of five VEGF-C single-nucleotide polymorphisms (SNPs) combined were also related to the risk of HCC. Conclusions: Our results suggest that the VEGF-C rs1485766 SNP and either of five haplotypes combined might contribute to a prediction of susceptibility to HCC. The genetic polymorphism of VEGF-C rs7664413 might be a predictive factor for advanced-stage HCC.