A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk

To identify risk variants for colorectal cancer (CRC), we conducted a genome-wide association study, genotyping 550,163 tag SNPs in 940 individuals with familial colorectal tumor ( 627 CRC, 313 advanced adenomas) and 965 controls. We evaluated selected SNPs in three replication sample sets ( 7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 ( involved in TGF-beta and Wnt signaling) associated with CRC. Across the four sample sets, the association between rs4939827 and CRC was highly statistically significant ( P-trend 1.0 x 10(-12)).