It seems that chronic inflammation that strongly predisposes for cancer formation [81], and hypoxia [82] which characterizes the fast growing cancer cells are the two main driving forces that lead to overexpression of TG2 in cancer cells, since TG2 expression is directly regulated by those pro-inflammatory cytokines that activate NF-κB, by TGF-β, and by the hypoxia activated HIFs. This evidence concerns the gene TGM2 and cancer.