SMAD7基因非编码区遗传多态对云南汉族人群结直肠癌患病的影响

发布时间：2018-05-31 15:16

本文选题：结直肠癌 + SMAD7基因　；参考：《云南大学》2015年硕士论文

【摘要】：背景：结直肠癌是世界上最常见的恶性肿瘤之一,发病率仅次于肺癌和乳腺癌,且呈稳定增长趋势。目前结直肠癌的发病机理尚未完全阐明,但病因学研究表明,结直肠癌的发生是一个多阶段、多步骤、多基因参与的过程,环境因素和遗传因素的联合作用导致了结直肠癌的发生。 Smad7是转化生长因子-β(TGF-β)信号转导通路的抑制元件,可选择性抑制TGF-β信号转导通路。而TGF-β信号转导通路的异常同结肠直肠癌、胰腺癌、肺癌、皮肤癌等多种肿瘤的发生有关。因此,Smad7也被认为是结肠直肠癌的一个候选基因。全基因组关联研究在SMAD7基因上识别了几个与结直肠癌相关的单核苷酸多态位点,但关于这些位点对结肠直肠癌发病的影响作用,来自不同研究小组的结果却不一致,表现出该基因遗传多态对结直肠癌易感影响的人群差异。但云南人群的相关研究数据尚缺乏。本研究即是期望对SMAD7基因的单核苷酸多态对云南汉族结直肠癌的影响进行初步评估。方法：本研究共纳入577例病例样本和584例正常对照样本,样本采自云南省第一人民医院,均为云南汉族人群。用酚-氯仿抽提法提取DNA,用PCR-RFLP方法对SMAD7基因非编码区的5个标签SNPs rs11874392、rs12953717、rs3736242、rs1316447和rs16950113(前4个在内含子区,第5个在3’UTR)位点进行基因型分型,用logistic回归分析检测遗传变异(等位基因,基因型和单倍型)与结直肠癌之间的关联性。结果： 1.单位点的五种遗传模式分析得到基本一致的影响作用结果：内含子区rs11874392和rs3736242的A等位基因为结直肠癌患病的风险因素；同样是内含子区的rs12953717和rs1316447的T等位基因和3’UTR rs16950113的C等位基因为结直肠癌的保护因素。2.进行直肠癌和结肠癌分层分析,结果显示：rs11874392和rs3736242在不同遗传模型下基本都同样表现出增加直肠癌和结肠癌患病风险的关联性；rs1316447在不同遗传模型下都同样表现降低结肠癌和直肠癌发病作用的关联性,而rs12953717仅表现出对直肠癌风险降低的作用；rs16950113则在任何一种遗传模型下都与结肠癌或直肠癌无关联。3.按照rs16950113-rs11874392-rsl2953717-rs1316447-rs3736242的单倍型结构,无论是结直肠癌综合分析还是结肠癌和直肠癌分别分析,6种主单倍型均表现出与结直肠癌的关联：H1、H4和H6单倍型为结肠癌和直肠癌的保护单倍型,H2、H3和H5单倍型为结肠癌和直肠癌的风险单倍型。结论：我们的研究结果提示,SMAD7基因是一个重要的结直肠癌候选基因,其上非编码区的遗传多态对结直肠癌发病的影响值得进一步关注。
[Abstract]:Background: colorectal cancer is one of the most common malignant tumors in the world. At present, the pathogenesis of colorectal cancer has not been fully elucidated, but etiological studies have shown that the occurrence of colorectal cancer is a multi-stage, multi-step, multi-gene involved process. The combination of environmental and genetic factors leads to the progression of rectal cancer. Smad7 is an inhibitory element of TGF- 尾) signal transduction pathway and can selectively inhibit TGF- 尾 signal transduction pathway. The abnormal signal transduction pathway of TGF- 尾 is related to the occurrence of many kinds of tumors, such as colorectal cancer, pancreatic cancer, lung cancer, skin cancer and so on. So Smad7 is also considered a candidate gene for colorectal cancer. The genome-wide association study identified several single nucleotide polymorphic loci associated with colorectal cancer on SMAD7 genes, but the results from different research groups were inconsistent as to the effects of these loci on the pathogenesis of colorectal cancer. The genetic polymorphism of the gene affected susceptibility to colorectal cancer in different populations. However, the relevant research data of Yunnan population is still lacking. This study is intended to evaluate the effect of single nucleotide polymorphism of SMAD7 gene on colorectal cancer in Yunnan Han nationality. Methods: a total of 577 cases and 584 normal controls were collected from the first people's Hospital of Yunnan Province. SNPs rs11874392rs12953717, rs3736242, rs1316447 and rs169501143 (the first four in intron region and the fifth in 3UTRR) were extracted by phenol-chloroform extraction method. The genotypes of SNPs rs11874392rs12953717 and rs169501143 (the first four were in intron region and the fifth in 3UTRs) were detected by logistic regression analysis. Genotypes and haplotypes) are associated with colorectal cancer. Results: 1. The results of analysis of five genetic patterns at unit point were consistent: allele A of intron region rs11874392 and rs3736242 were risk factors of colorectal cancer. The T allele of rs12953717 and rs1316447 and the C allele of 3'UTR rs16950113 are the protective factors of colorectal cancer. Stratified analysis of rectal and colon cancer, The results showed that in different genetic models, both the two groups showed the same association in increasing the risk of colorectal cancer and colon cancer. Rs1316447 showed the same association in reducing the incidence of colon cancer and rectal cancer in different genetic models. Rs12953717 only showed a reduced risk for rectal cancer. Rs16950113 was not associated with colon or rectal cancer in any genetic model. According to the haplotype structure of rs16950113-rs11874392-rsl2953717-rs1316447-rs3736242, The six major haplotypes were associated with colorectal cancer. The haplotypes of H1H4 and H6 were the protective haplotypes of colon cancer and rectal cancer. The haplotypes H2H3 and H5 haplotypes were found to be colorectal cancer haplotypes. Haplotypes of bowel cancer and rectal cancer. Conclusion: our results suggest that SMAD7 gene is an important candidate gene for colorectal cancer.
【学位授予单位】：云南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.34

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