As mentioned above, accumulating researches validate that colorectal cancer cells originate from ISCs, however, ISCs are apt to differentiate and Lgr5 expression is reduced in tissue damage (like radiation, DSS, and infection) and inflammation (such as IFN-γ, IL-17, and IL-13) state, which are key risk factors for colorectal tumorigenesis. This evidence concerns the gene LGR5 and infection.