When the tumor size becomes more than 1–2 mm3, the central tumor cells are subjected to a hypoxic microenvironment; this induces the activation of the hypoxia-inducible factor (HIF) to facilitate its binding to the hypoxia-response element (HRE) to induce cell proliferation and expression of angiogenesis factors such as epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). This evidence concerns the gene VEGFA and neoplasm.