VEGF polymorphisms are associated with an increasing risk of developing renal cell carcinoma

Purpose: 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.

Materials and methods: 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.

Results: 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).

Conclusions: 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.