The studies from us and others have demonstrated that the increase of cytokines (e.g., COX2, NF-κB, TNFα, IL-1β, IL6, etc.), CXCLs and CXC receptors (CXCRs) could be the cause of malignant transformation of chronic colitis, which shows defect of mucosa barrier, causing gut microbiota disorder and enhancement of inflammation, resulting in genetic mutations, epigenetic alteration (e.g., DNA methylation, histone acetylation and miRNAs, etc.)and oncogenic signaling activation (e.g., Wnt, Ras, PI3K/AKT/STAT3, etc.)[21,28,29,30]. The gene discussed is TNF; the disease is Chronic colitis.