The Influence Of SMAD7Gene Noncoding Region Genetic Polymorphisms On Risk Of Colorectal Cancer In Yunnan Han Population

Background:Colorectal cancer (CRC) is one of the most common malignant tumor estimated2.8million patients in the world, and its incidence is just next to lung cancer and gastric carcinoma. Moreover, colorectal cancer showed a steady growth trend with about one million new cases increased each year. Pathogenesis of colorectal cancer has not been fully elucidated, but a lot of etiology studies have shown that the development of colorectal cancer is a multi-stage, multi-step, multi-gene involved process, and the joint action of environment factors and genetic factors result in the occurrence of colorectal cancer.SMAD7is an inhibitory SMAD and a negative regulator of the transforming growth factor β (TGF-β) signaling pathway, which plays important roles in tumor initiation, invasion and metastasis. Currently, much attention has been drawn to those SNPs associated with CRC within SMAD7gene. But most of these studies are carried out in western populations, only a few assessed in Chinese. Moreover, some results of SNPs associated with CRC studies led to contradictory conclusions about the effect of the SNPs on susceptibility to CRC.Thus, to analyze whether those SNPs located in SMAD7gene are correlated with CRC in Chinese Han as that in western populations, we performed this association analysis with5SNPs in SMAD7gene in Yunnan Han nationality.Methods:In this study, a total of577CRC cases and584cancer-free control were recruited from the First People’s Hospital of Yunnan Province. All individuals are of Han nationality in Yunnan. Genotyping for five tagging SNPs of SMAD7gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The association between the genetic variation (Allele, Genotype and Haplotype) and CRC disease was examined by logistic regression.Results:1. The minor allele of both intronic SNPs rs11874392and rs3736242were detected association with a significant increased risk with CRC under different genetic models; while the minor allele of other two intronic SNPs rs12953717and rs1316447, and the3’UTR SNP rs16950113were all found associated with a decreased risk with CRC under part of genetic models.2. After classified CRC into rectal cancer and colon cancer. the strong correlation still remained in rs11874392and rs3736242for their increased risk with both rectal cancer and colon cancer; and the decreasing effect with both rectal cancer and colon cancer was also observed in rs1316447, while that only found with rectal cancer in rs12953717. But it showed that neither colon cancer nor rectal cancer associated with rs16950113polymorphism in any genetic model.3. Composed of five SNPs by rs16950113-rs11874392-rs12953717-rsl316447-rs3736242, there were six major haplotypes were detected. Among these haplotypes, HI, H4and H6shown as the protective factors of CRC, and H2, H3and H5shown as the risk factors of CRCConclusion:Our study confirmed that the effect of SMAD7SNPs on CRC should not be neglected.