A case-control study: association of SMAD7 single nucleotide polymorphisms with colorectal cancer in the Han population

Recent genome-wide studies and analyses of the TGF-beta pathway have identified a risk locus among the Caucasian population for colorectal cancer (CRC). This risk locus is located at 18q21, which maps to the SMAD7 gene. As a result, the CRC susceptibility loci identified thus far among Caucasians cannot be used to predict the risk of CRC in Chinese Han population. A Chinese Han population case-control study was conducted to assess genetic associations with CRC risk. Four SNPs in the SMAD7 gene were genotyped among 276 CRC cases and 385 controls using the Sequenom Mass-ARRAY (R) platform. The associations of the SNP frequencies with CRC were analyzed by Chi-square (X-2) tests, SNPStats software, and SHEsis software. Based on X-2 tests, rs12956924 (P = 0.010), rs11874392 (P = 0.003) and rs4939827 (P = 0.026) correlate with CRC risk. We found that allele "A" of rs12956924 may reduce the risk of CRC (P = 0.048) and rectal cancer (P = 0.03) using the log-additive model genetic analysis. The minor allele "A" of rs11874392 may increase the risk of CRC (P = 0.017), colon (P = 0.038) and rectal (P = 0.03) cancers based on the log-additive model. And we also found the minor allele "T" of rs4939827 was also significantly associated with increase CRC risk (P = 0.026) and colon cancer (P = 0.048) under the dominant model. No significant associations were observed for the rs1873190 SNP evaluated in the SMAD7 gene. Our data add evidence supporting the genes SMAD7 is associated with CRC susceptibility and found the differences of susceptibility loci between colon and rectal cancers in Chinese Han population. Collectively, these data suggest that SMAD7 SNP may be considered as potential diagnostic biomarkers in patients with colorectal cancer in Chinese Han populations.