Damavand Behzad, Derakhshani Shaghayegh, Saeedi Nastaran, Mohebbi Seyed Reza, Milanizadeh Saman, Azimzadeh Pedram, Aghdaie Hamid Asadzadeh, Zali Mohammad Reza
Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail :
Asian Pac J Cancer Prev. 2015;16(1):41-4. doi: 10.7314/apjcp.2015.16.1.41.
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.
基于全基因组关联研究（GWAS），已注意到SMAD7（果蝇抗五体不全蛋白同源物7）内含子3中的几个变体（如单核苷酸多态性（SNP）），即rs12953717、rs4464148和rs4939827之间的连锁与结直肠癌（CRC）易感性有关。在本研究中，我们基于病例对照研究调查了487名伊朗个体中rs12953717和rs4464148与CRC风险的关系。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行SNP基因分型，为确认结果，对10%的基因分型病例进行了RFLP测序。比较病例组和对照组，我们发现rs4464148 SNP与较低的CRC风险之间存在显著关联。AG基因型显示风险降低，优势比为0.635（校正OR = 0.635，95%可信区间：0.417 - 0.967，p = 0.034）。在评估的两组人群中，SMAD7基因rs12953717 TT基因型的分布没有显著差异（校正OR = 1.604，95%可信区间：0.978 - 2.633，p = 0.061）。另一方面，rs12953717 T等位基因与CRC风险显示出统计学上的显著关联（校正OR = 1.339，95%可信区间：1.017 - 1.764，p = 0.037）。总之，我们发现CRC风险与rs4464148 AG基因型之间存在显著关联。此外，rs12953717 T等位基因可能是一个风险因素。这种关联可能是由前体mRNA的可变剪接引起的。虽然我们在受影响的女性中观察到与rs4464148 GG基因型有很强的关联，但在CRC男性患者中未检测到相同的关联。
