A Single Nucleotide Polymorphism in the Vascular Endothelial Growth Factor Gene Is Associated with Recurrence of Hepatocellular Carcinoma after Transplantation

Background

Vascular endothelial growth factor (VEGF), an important regulator of angiogenesis and vascular permeability, is involved in various steps of many malignancies. Gene polymorphisms within the gene encoding VEGF have been shown to be independently associated with an adverse outcome in various malignancies including hepatocellular carcinoma (HCC) with resection. However, no data are available for HCC treated with liver transplantation (LT). Therefore, we investigated association of VEGF genomic polymorphisms with risk for developing HCC and tumor recurrence after LT.

Methods

Seven polymorphisms in the VEGF gene (rs699947, rs1570360, rs2010963, rs3024997, rs3025010, rs3025035, rs3025039) were examined in 93 HCC patients treated with LT and 99 controls using Applied Biosystems SNaP-Shot and TaqMan technology. Cox proportional hazard model was used to estimate the hazard ratios associated with polymorphisms.

Results

The association between rs3025035 and recurrence was significant (p=0.003). However, no other SNP in VEGF was associated with recurrence. Interestingly, we found that patients with rs3025035 CT heterozygous was independently associated with a shortened recurrence-free survival (odds ratio: 3.3; 95% confidence interval: 1.8–6.0; p<0.001).

Conclusions

Our data suggest that polymorphism rs3025035 in the VEGF gene may be a potential genetic marker for HCC recurrence in LT patients.

Key Words: Hepatocellular carcinoma, Polymorphisms, Recurrence, Vascular endothelial growth factor