['Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry.', '23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression.', 'Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12-1.49), and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70-0.92) were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps.'] Are genetic variations in SMAD7 associated with colorectal cancer risk in the colon cancer family registry?