title: Intronic polymorphisms of the SMAD7 gene in association with colorectal cancer.
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.
authors: Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail : azimzadeh@sbmu.ac.ir.
authors: Behzad
authors: B
authors: Damavand
authors: Shaghayegh
authors: S
authors: Derakhshani
authors: Nastaran
authors: N
authors: Saeedi
authors: Seyed Reza
authors: SR
authors: Mohebbi
authors: Saman
authors: S
authors: Milanizadeh
authors: Pedram
authors: P
authors: Azimzadeh
authors: Hamid Asadzadeh
authors: HA
authors: Aghdaie
authors: Mohammad Reza
authors: MR
authors: Zali
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007492:Iran; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D051906:Smad7 Protein / Q000235:genetics*
chemical_list: C497806:SMAD7 protein, human; D051906:Smad7 Protein