Studies have shown that increased levels of S1P were detected in the SPHK2 knockout mice, which exacerbates chronic intestinal inflammation, and through S1PR1–NF-κB-IL-6 (interleukin-6)–STAT3 (activator of transcription factor 3) signal leads to the development of colitis related cancers (54). This evidence concerns the gene NFKB1 and cancer.