Breast cancer is the most common cancer in females and the leading cause of cancer death in women worldwide. Angiogenesis, the formation of new blood vessels, plays an important role in the development and progression of breast cancer. Vascular endothelial growth factor A (VEGFA), the key modulator of angiogenesis, is highly expressed in cancer tissue and correlates with its more aggressive features. Polymorphisms of VEGFA alter the levels of expression and subsequently influence the susceptibility and aggressiveness of breast cancer. Assessment of VEGFA polymorphisms may be used for the identification of patients suitable for anti-VEGFA therapy.

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 semi‑quantitative RT‑PCR. 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 II‑IV. Individuals with ‑634C/C had lower disease‑free 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.