Given the SMAD7's role in the TGF-β signaling pathway [12] and the significant between-study heterogeneity in the reported association between SMAD7 SNPs and CRC risk, we looked to confirm the association between SMAD7 SNPs and CRC risk in a large family-based case-control study based on the multi-center Colon Cancer Family Registry (Colon CFR), and to examine gene X environmental interactions to identify risk/protective factors that may affect the association between SMAD7 SNPs and CRC risk. The gene discussed is SMAD7; the disease is colorectal carcinoma.