Vascular endothelial growth factor ­634G/C polymorphism is associated with increased breast cancer risk and aggressiveness.

Polymorphisms in the promoter and 5' untranslated region of vascular endothelial growth factor (VEGF) have been associated with VEGF levels. To investigate the role of VEGF polymorphisms in breast cancer, the VEGF ­2578C/A, ­1498C/T, ­1154G/A and ­634G/C polymorphisms were genotyped in 483 breast cancer patients and 524 healthy controls. VEGF mRNA levels in breast cancer tissue were determined using semi­quantitative RT­PCR. The genotypes, ­634G/C and ­634C/C, were associated with an increased risk for breast cancer when compared with the ­634G/G genotype. The VEGF ­634G/C genotype was associated with tumor size >20 mm, perineural invasion and stage II­IV. Individuals with ­634C/C had lower disease­free survival. Patients with the VEGF ­634C/C genotype exhibited the highest VEGF mRNA levels. High VEGF mRNA expression correlated with tumor size >20 mm, presence of lymphovascular invasion and axillary nodal metastasis. These observations suggested that VEGF ­634G/C polymorphisms have a significant role in breast cancer susceptibility and aggressiveness.