本文選題：Caveolin-1　切入點：食管腫瘤　出處：《山東大學》2015年碩士論文　論文類型：學位論文

【摘要】：研究背景及目的食管鱗癌(ESCC)是世界上最常見的惡性腫瘤之一,其在中國的患病率和死亡率相對偏高。除環(huán)境危險因素吸煙、飲酒、飲用熱茶外,有證據(jù)表明遺傳因素,如單核苷酸多態(tài)性(SNPs),可能促進食管鱗癌的發(fā)生。Caveolin-1(CAV1)基因是Caveolin基因家族中主要的成員,其在腫瘤的發(fā)生、發(fā)展及轉(zhuǎn)移過程中發(fā)揮重要的作用。在食管鱗癌組織中,CAV1表達水平升高與ESCC的浸潤深度、淋巴結(jié)轉(zhuǎn)移和預后密切相關(guān)。近期有研究表明,CAV1基因的單核苷酸多態(tài)性與腫瘤有關(guān)。本研究旨在探討CAV1基因多態(tài)性位點C239A(rs 1997623)、G14713A (rs3807987)、G21985A (rs12672038)、T29107A (rs7804372)的基因多態(tài)性與食管鱗癌易感性的關(guān)聯(lián)。方法該病例-對照研究包括427例食管鱗癌患者和427例按性別、年齡(±1歲)頻數(shù)匹配的正常對照者。每人抽取外周血5m1并提取基因組DNA。采用聚合酶鏈反應一限制性片段長度多態(tài)性法(polymerase chain reaction and restriction fragment length polymorphism, PCR-RFLP)檢測CAV1基因多態(tài)位點C239A (rs1997623)、 G14713A(rs3807987)、G21985A(rs 12672038)、T29107A (rs7804372)的基因型。采用以貝葉斯分析方法為原理的PHASE軟件構(gòu)建單倍體型,并計算各基因多態(tài)性位點的單倍體型頻率。采用條件Logistic回歸模型分析基因多態(tài)性位點的基因型、等位基因及單倍型與食管鱗癌發(fā)病風險的相關(guān)性。根據(jù)病例組和對照組的年齡、性別、吸煙史、飲酒史進行分層分析,評估CAV1基因多態(tài)性位點G14713A和T29107A的基因型對食管鱗癌易感性的影響。結(jié)果病例組和對照組在年齡、吸煙、飲酒三方面的分布無統(tǒng)計學差異(P=0.893,P=0.154,P=0.101)；病例組G14713A位點的基因型AG和AA及等位基因A的頻率顯著高于對照組(AG,OR=1.921,95%CI=1.292-2.855,P=0.00004;AA, OR=3.199,95%CI=1.542-6.635,P=0.00007;A等位基因,OR=2.067,95%CI =1.481-2.885,p0.00001);相反,病例組T29107A位點的基因型AA以及等位基因A明顯低于對照組(AA,OR=0.403,95%CI=0.173-0.857,P=0.00700;A等位基因,OR=0.601,95%CI=0.421-0.857,P=0.00034)；而C239A和G21985A位點的基因型和等位基因頻率在兩組中的分布差異均無統(tǒng)計學意義(P0.05)。單倍型分析表明：單倍型CAAT和CAGT顯著增加了食管鱗癌的發(fā)病風險(CAAT,OR=3.968,95%CI=1.251.12.579,P=0.00285;CAGT,OR= 3.345,95%CI=1.882-5.944,P0.00001),而單倍型CGGA降低了食管鱗癌的易感性(OR=0.176,95%CI=0.071-0.437,P0.00001).分層分析結(jié)果表明：多態(tài)性位點G14713A可同時增加男性(P=0.00344)、女性(P=0.00009)60歲(P=0.00013)、≥60歲(P=0.00021)、不吸煙及不飲酒(P0.00001,P=0.00003)個體的食管鱗癌發(fā)病風險,而多態(tài)性位點T29017A可同時降低女性(P=0.00013)、不吸煙(P=0.00140)和不飲酒(P=0.00027)個體罹患食管鱗癌的可能性。結(jié)論CAV1基因多態(tài)位點C239A.G14713A.G21985A.T29107A均具有多態(tài)性；G14713A和T29107A位點的多態(tài)性與食管鱗癌易感性相關(guān),而C239A和G21985A位點的多態(tài)性與食管鱗癌易感性無關(guān)；單倍體型CAAT和CAGT是食管鱗癌的危險因素,而單倍體型CGGA是食管鱗癌的保護因素；多態(tài)位點G14713A和T29107A與食管鱗癌易感性的關(guān)聯(lián)性在女性患者及不吸煙不飲酒的患者中更加顯著；多態(tài)性位點G14713A和T29107A將成為有利于食管鱗癌的早期診斷、個體化治療的有效遺傳標記物。
[Abstract]:Background and objective: esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumor in the world, the Chinese morbidity and mortality is relatively high. In addition to smoking, environmental risk factors of drinking, drinking hot tea, there is evidence that genetic factors, such as single nucleotide polymorphisms (SNPs), may promote the occurrence of esophageal squamous cell carcinoma (.Caveolin-1 CAV1) gene is one of the main members of Caveolin gene family, in tumorigenesis, play an important role in the process of development and metastasis. In esophageal squamous cell carcinoma, the expression level of CAV1 ESCC increased with the depth of invasion, lymph node metastasis and prognosis of closely related. Recent studies have shown that CAV1 gene single nucleotide polymorphism and tumor. This study aimed to investigate the CAV1 gene polymorphism of C239A (RS 1997623), G14713A (rs3807987), G21985A (rs12672038), T29107A (rs7804372) gene polymorphism and susceptibility to esophageal squamous cell carcinoma The association method. The case-control study included 427 cases of patients with esophageal squamous cell carcinoma and 427 cases by gender, age (+ 1 years) normal controls were frequency matched. Each extraction of peripheral blood 5m1 and genomic DNA. by polymerase chain reaction restriction fragment length polymorphism method (polymerase chain reaction and restriction fragment length polymorphism, PCR-RFLP) detection of CAV1 gene C239A (rs1997623), G14713A (rs3807987), G21985A (RS 12672038), T29107A (rs7804372) genotype. By using Bias analysis method to construct haplotype as the principle of PHASE software, and the calculation of haplotype frequency of each gene polymorphism loci. The gene type conditional Logistic regression analysis of the correlation between the gene polymorphism site, allele and haplotype with risk of esophageal squamous cell carcinoma. According to the case and control groups were age, gender, Smoking history, drinking history were stratified analysis, evaluation of effects of genotype CAV1 gene polymorphism of G14713A and T29107A on the susceptibility of esophageal squamous cell carcinoma. The results of the case group and the control group in age, smoking, drinking and distribution in three aspects of no significant difference (P=0.893, P=0.154, P= 0.101); group G14713A loci AG and AA and A allele frequency was significantly higher than that of the control group (AG, OR=1.921,95%CI=1.292-2.855, P=0.00004; AA, P=0.00007; OR=3.199,95%CI=1.542-6.635, A alleles, OR=2.067,95%CI =1.481-2.885, p0.00001); on the contrary, the case group T29107A locus genotype AA and allele A was significantly lower than the control group (AA, OR=0.403,95%CI=0.173-0.857, P=0.00700; A allele, OR=0.601,95%CI=0.421-0.857, P=0.00034); while there were no statistical difference of distribution of C239A and G21985A loci genotype and allele frequencies in the two groups in the Meaning (P0.05). Haplotype analysis showed that haplotype CAAT and CAGT significantly increased the risk of esophageal squamous cell carcinoma (CAAT, OR=3.968,95%CI=1.251.12.579, P=0.00285; CAGT, OR=, 3.345,95%CI=1.882-5.944, P0.00001) and CGGA haplotype decreased susceptibility to esophageal squamous cell carcinoma (OR=0.176,95%CI=0.071-0.437, P0.00001). The hierarchical analysis results showed that the polymorphism of G14713A can also increase male (P=0.00344), female (P=0.00009) 60 (P=0.00013), more than 60 years old (P=0.00021), not smoking and not drinking (P0.00001, P=0.00003) individual risk of esophageal squamous cell carcinoma, and the polymorphism of T29017A can also reduce the female (P=0.00013), smoking (P=0.00140) and (P=0.00027) the possibility of individual drinking suffering from esophageal squamous cell carcinoma. Conclusion CAV1 gene C239A.G14713A.G21985A.T29107A polymorphism sites were polymorphic; the polymorphism of G14713A and T29107A loci in esophageal squamous cell carcinoma Association between C239A and G21985A polymorphisms has nothing to do with the susceptibility of esophageal squamous cell carcinoma; haploid type CAAT and CAGT are the risk factors of esophageal squamous cell carcinoma, and the CGGA haplotype is a protective factor for esophageal squamous cell carcinoma; G14713A and T29107A polymorphisms and susceptibility of esophageal squamous cell carcinoma associated not drinking in women and non-smoking patients more significant; polymorphic loci of G14713A and T29107A will be conducive to the early diagnosis of esophageal squamous cell carcinoma, effective genetic markers for individualized treatment.

【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R735.1

【參考文獻】

相關(guān)期刊論文 前1條

1 Yuwei Zhang;;Epidemiology of esophageal cancer[J];World Journal of Gastroenterology;2013年34期

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本文編號：1611223