High Vascular Endothelial Growth Factor (VEGF) Level and Matrix Metalloproteinase-9 (MMP-9) Gene Polymorphism (rs17576) Increase Metastasis Risk in Breast Cancer: A Cross-sectional Study

Metastatic breast cancer is a serious health problem with a high mortality rate. Matrix metalloproteinase-9 (MMP-9) gene polymorphisms (rs17576) and Vascular Endothelial Growth Factor (VEGF) expressions enhance the process of angiogenesis and the risk of metastatic breast cancer. However, there is still a lack of studies on this topic. Therefore, the purpose of the study was to evaluate the association between MMP-9 gene polymorphism and VEGF levels with the risk of metastasis in breast cancer patients. This is a cross-sectional study involving breast cancer patients in Bali. The Polymerase Chain Reaction and DNA sequencing techniques are used to analyze the MMP-9 gene polymorphisms (rs17576), while the ELISA method is used to measure the VEGF levels. The data was then analyzed using SPSS ver.26. This study involved 64 breast cancer patients. The median (IQR) of the VEGF level is 85.17 (57.82 – 124.73) pg/mL. It was found as much as 42.2% of the patients experienced MMP-9 gene polymorphism. Receiver operating curve (ROC) analysis found the optimum cut-off of VEGF level is 98.11 pg/mL with a sensitivity of 66.7% and specificity of 81.4% (p=0.007). This study found that breast cancer patients with high VEGF levels ( 98.11 pg/mL) (p=0.001; AOR: 8.93; 95%CI: 2.41 – 33.08) have a higher risk of metastasis. In conclusion, breast cancer patients with high VEGF levels have a higher risk of developing metastasis.