Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
BMC Med Genomics. 2022 Jan 11;15(1):8. doi: 10.1186/s12920-021-01150-3.
Colorectal cancer (CRC) is one of the common cancers with a high mortality rate worldwide. In Iran, there has been a trend of increased incidence of colorectal cancer in the last three decades that necessitates the early diagnosis. Genetic factors have an influential role in its etiology along with the conventional risk factors such as age, diet, and lifestyle. Results from GWAS have shown significant associations between SMAD7 gene variants and risk of CRC. This study aimed to assess the association of certain polymorphisms as well as haplotypes of this gene and risk of colorectal cancer.
This study was designed as a case-control association study. After obtaining ethical approval and informed consent, blood samples from 209 patients with colorectal cancer were collected and DNA was extracted. Four variants: rs4939827, rs34007497, rs8085824 and rs8088297 were genotyped using ARMS-PCR method.
SMAD7 rs4939827 in the recessive and co-dominant models was associated with colorectal cancer risk [TT/CT + CC: OR = 2.90, 95%CI (1.38-6.09), p = 0.005; CC + TT/CT: OR = 1.66, 95%CI (1.00-2.75), p = 0.01]. Haplotype analysis indicated that some SNP combinations including two for-SNPs haplotypes of T-T-C-C and T-C-C-A were significantly associated with CRC risk.
Based on the identified association of SMAD7 gene variations and haplotypes with colorectal cancer risk in our population, genetic variations in this gene region may have a role in CRC development. This data may shed light on the genetic predisposition of CRC which involves different pathways including TGF-β.
结直肠癌（CRC）是全球死亡率较高的常见癌症之一。在伊朗，过去三十年 CRC 的发病率呈上升趋势，因此需要早期诊断。遗传因素及其与年龄、饮食和生活方式等传统危险因素一起对其发病机制有影响。全基因组关联研究的结果表明 SMAD7 基因变异与 CRC 风险之间存在显著关联。本研究旨在评估该基因的某些多态性以及单倍型与结直肠癌风险的关系。
本研究设计为病例对照关联研究。在获得伦理批准和知情同意后，采集了 209 例结直肠癌患者的血液样本并提取 DNA。使用 ARMS-PCR 方法对 4 个变体(rs4939827、rs34007497、rs8085824 和 rs8088297)进行基因分型。
SMAD7 rs4939827 在隐性和共显性模型中与结直肠癌风险相关[TT/CT+CC：OR=2.90，95%CI(1.38-6.09)，p=0.005；CC+TT/CT：OR=1.66，95%CI(1.00-2.75)，p=0.01]。单倍型分析表明，包括两个前 SNP 单倍型 T-T-C-C 和 T-C-C-A 的一些 SNP 组合与 CRC 风险显著相关。
基于我们人群中 SMAD7 基因变异和单倍型与结直肠癌风险的关联，该基因区域的遗传变异可能在 CRC 发生中起作用。这些数据可能揭示了结直肠癌的遗传易感性，涉及 TGF-β 等不同途径。
