VEGF Polymorphisms are Associated With an Increasing Risk of Developing Renal Cell Carcinoma

Abstract

Vascular endothelial cell growth factor is studied in different malignant tumors as a key endothelial cell mitogen. Many single nucleotide polymorphisms in the VEGF gene have been described. We compared VEGF gene polymorphisms between a control group and a renal cancer group. This study was performed in 202 control, white, healthy blood donors (control group) and in 51 consecutive patients with renal cell carcinoma. We studied VEGF genotype polymorphisms at positions -2549, -460, -1154, +405 and +936 using polymerase chain restriction fragment length polymorphism, and looked for correlations with clinical data. No association was found between VEGF gene polymorphism and renal cell carcinoma prognostic parameters. However, in contrast as observed for controls and other polymorphisms the patient group displayed a heterozygote excess (p = 0.0179, 35.9% more than that expected) at the -460 polymorphism. Comparing the control group and the renal cell carcinoma group we detected a significantly increased risk of renal cell carcinoma in subjects with the C-460T polymorphism. T carrier genotypes and the T allele increased the risk of renal cell carcinoma with an OR of 14.15 (95% CI 1.900-105.41, p = 0.0017) and 2.14 (95% CI 1.34-3.419, p = 0.0018), respectively. The genotype at the -2549 polymorphism exhibited a nonsignificant trend for increased risk but the D allele was significantly associated with increased risk (p = 0.0305). Our results suggest that the -460 polymorphism is a risk factor for renal cancer. An individual screening test could be proposed for high risk populations.