SMAD7 and colorectal carcinoma: In another study, Fortini et al. suggested that the associated CRC risk at 18q21.1 is due to four functional variants (rs6507874, rs6507875, rs8085824, and rs58920878) which regulate SMAD7 expression and potentially perturb a BMP negative feedback loop in TGFb/BMP signaling pathways (17).