P-0179 - Intronic SMAD7 gene polymorphisms, rs12953717 and rs4464148, in association with risk of Colorectal Cancer

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Shaghayegh Derakhshani
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors S. Derakhshani1, S. Milanizadeh1, P. Azimzadeh2, B. Damavand1, N. Saeedi1, R. Mohebbi Seyed1
  • 1Gastroenterology and Liver Diseases Research Center, Tehran/IR
  • 2Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran/IR



Based on Genome-wide association studies (GWAS) a linkage between several variants and the susceptibility to colorectal cancer (CRC) such as Single nucleotide polymorphisms (SNPs) in intron 3 of SMAD7 (mothers against decapentaplegic homolog7) were rs12953717 and rs4464148. SMAD7 is an inhibitory SMAD, and due to its role as a negative regulator of the TGF-ß signaling pathway; it elevates the anti-inflammatory effects of TGF-ß pathway. Thus the act of SMAD 7 could remarkably decrease the TGF-ß signaling and results in increasing the risk of cancer. Molecular biology and studying the signaling pathways are now going to make an evolutionary challenge through presenting the new generation of medicine which is now growing by the advances in SNPs researches and could form the personalized medicine.


In this study we investigated the relationship of rs12953717, rs4464148 and risk of CRC among 487 Iranian individuals based on a case-control study. Genomic DNA was extracted from 5 mL of peripheral blood drawn from study participants using a standard salting out method. Genotyping of SNPs was performed by PCR-RFLP method and for approving the outcomes 10% of genotyping results with RFLP, were sequenced.


Comparing the case and control group, indicates significant association between the rs4464148 SNP and lower risks for CRC. The AG genotype showed decreased risk for colorectal cancer with odds ratio 0.635 (adjusted OR = 0.635, 95% CI: 0.417-0.967, P = 0.034). There was no significant difference in the distribution of SMAD7 gene rs12953717 TT genotype between two groups of the population evaluated (adjusted OR = 1.604, 95% CI: 0.978-2.633, P = 0.061). On the other hand, rs12953717 T allele shows statistically significant association with CRC risk (adjusted OR = 1.339, 95% CI: 1.017-1.764, P = 0.037). The genotyping and allele distribution data analyzing base on gender status was performed, which in women, the rs4464148 GG genotype was statistically associated with an increased risk of colon cancer (adjusted OR = 3.499, 95% CI: 1.382-8.859, P = 0.008). For men P value of the rs4464148 AG genotype was 0.050. This stratified analysis has revealed no association between gender difference and rs12953717.


The results showed that rs4464148 AG genotype may act as a protective factor as opposed to rs12953717 T allele which may act as a risk factor in susceptibility to CRC. Our findings indicated that although the mentioned SNPs for SMAD 7 in this study were intronic, they showed a significant association with CRC risk. SNPs have revealed as significant markers for predicting susceptibility to serious diseases like cancer and a road to get to personalized medicine. Since colorectal cancer is one of the leading causes of death in the world and there are so many findings regarding the influence of single polymorphisms on alternation the risk of CRC, more research on different SNPs whether intronic or exonic is needed.