Direct evidence for this assertion is provided by the fact that inactivating mutations in SMAD4 (Howe, et al., 1998) and BMPR1A (Howe, et al., 2001), which, like BMP4, are members of the TGF-β superfamily cause the rare juvenile polyposis syndrome, which carries a very high risk of CRC. Here, BMP4 is linked to colorectal carcinoma.