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Intronic Polymorphisms of the SMAD7 Gene in Association with Colorectal Cancer

  • Damavand, Behzad (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Derakhshani, Shaghayegh (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Saeedi, Nastaran (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Mohebbi, Seyed Reza (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Milanizadeh, Saman (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Azimzadeh, Pedram (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Aghdaie, Hamid Asadzadeh (Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Zali, Mohammad Reza (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences)
  • Published : 2015.02.04

Abstract

Based on genome-wide association studies (GWAS) a linkage between several variants such as single nucleotide polymorphisms (SNPs) in intron 3 of SMAD7 (mothers against decapentaplegic homolog7) were, rs12953717, rs4464148 and rs4939827 has been noted for susceptibility to colorectal cancer (CRC). In this study we investigated the relationship of rs12953717 and rs4464148 with risk of CRC among 487 Iranian individuals based on a case-control study. Genotyping of SNPs was performed by PCR-RFLP and for confirming the outcomes, 10% of genotyping cases were sequenced with RFLP. Comparing the case and control group, we have found significant association between the rs4464148 SNP and lower risk of CRC. The AG genotype showed decreased risk with and odds ratio of 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 showed a statistically significant association with CRC risk (adjusted OR=1.339, 95% CI: 1.017-1.764, p=0.037). In conclusion, we found a significant association between CRC risk and the rs4464148 AG genotype. Furthermore, the rs12953717 T allele may act as a risk factor. This association may be caused by alternative splicing of pre mRNA. Although we observed a strong association with rs4464148 GG genotype in affected women, we did not detect the same association in CRC male patients.

Keywords

SMAD7;single nucleotide polymorphism;cancer;TGF-${\beta}$;gender variation

Acknowledgement

Supported by : Shahid Beheshti University of Medical Sciences

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