Increased serum concentrations of TNF-α are present in several independent cancer types, despite malignant cells constitutively producing only small amounts of TNF: TNF-α produced chronically at low picogram levels in the tumor microenvironment, whether by tumor or stromal cells (or most likely both), may cause direct DNA damage, have anti-apoptotic or mitogenic activity, mediate tumor/stromal cell interactions, and induce a range of MMPs, cytokines, and chemokines that promote tumor development. This evidence concerns the gene TNF and neoplasm.