本文選題：結直腸癌 + SMAD7基因�。� 參考：《云南大學》2015年碩士論文

【摘要】：背景：結直腸癌是世界上最常見的惡性腫瘤之一,發(fā)病率僅次于肺癌和乳腺癌,且呈穩(wěn)定增長趨勢。目前結直腸癌的發(fā)病機理尚未完全闡明,但病因學研究表明,結直腸癌的發(fā)生是一個多階段、多步驟、多基因參與的過程,環(huán)境因素和遺傳因素的聯合作用導致了結直腸癌的發(fā)生。 Smad7是轉化生長因子-β(TGF-β)信號轉導通路的抑制元件,可選擇性抑制TGF-β信號轉導通路。而TGF-β信號轉導通路的異常同結腸直腸癌、胰腺癌、肺癌、皮膚癌等多種腫瘤的發(fā)生有關。因此,Smad7也被認為是結腸直腸癌的一個候選基因。 全基因組關聯研究在SMAD7基因上識別了幾個與結直腸癌相關的單核苷酸多態(tài)位點,但關于這些位點對結腸直腸癌發(fā)病的影響作用,來自不同研究小組的結果卻不一致,表現出該基因遺傳多態(tài)對結直腸癌易感影響的人群差異。但云南人群的相關研究數據尚缺乏。本研究即是期望對SMAD7基因的單核苷酸多態(tài)對云南漢族結直腸癌的影響進行初步評估。 方法：本研究共納入577例病例樣本和584例正常對照樣本,樣本采自云南省第一人民醫(yī)院,均為云南漢族人群。用酚-氯仿抽提法提取DNA,用PCR-RFLP方法對SMAD7基因非編碼區(qū)的5個標簽SNPs rs11874392、rs12953717、rs3736242、rs1316447和rs16950113(前4個在內含子區(qū),第5個在3’UTR)位點進行基因型分型,用logistic回歸分析檢測遺傳變異(等位基因,基因型和單倍型)與結直腸癌之間的關聯性。 結果： 1.單位點的五種遺傳模式分析得到基本一致的影響作用結果：內含子區(qū)rs11874392和rs3736242的A等位基因為結直腸癌患病的風險因素；同樣是內含子區(qū)的rs12953717和rs1316447的T等位基因和3’UTR rs16950113的C等位基因為結直腸癌的保護因素。2.進行直腸癌和結腸癌分層分析,結果顯示：rs11874392和rs3736242在不同遺傳模型下基本都同樣表現出增加直腸癌和結腸癌患病風險的關聯性；rs1316447在不同遺傳模型下都同樣表現降低結腸癌和直腸癌發(fā)病作用的關聯性,而rs12953717僅表現出對直腸癌風險降低的作用；rs16950113則在任何一種遺傳模型下都與結腸癌或直腸癌無關聯。3.按照rs16950113-rs11874392-rsl2953717-rs1316447-rs3736242的單倍型結構,無論是結直腸癌綜合分析還是結腸癌和直腸癌分別分析,6種主單倍型均表現出與結直腸癌的關聯：H1、H4和H6單倍型為結腸癌和直腸癌的保護單倍型,H2、H3和H5單倍型為結腸癌和直腸癌的風險單倍型。 結論：我們的研究結果提示,SMAD7基因是一個重要的結直腸癌候選基因,其上非編碼區(qū)的遺傳多態(tài)對結直腸癌發(fā)病的影響值得進一步關注。
[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.
【學位授予單位】：云南大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R735.34

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本文編號：1960251