Caveolin-1基因多态性与食管鳞癌易感性的关联性研究

发布时间：2018-03-14 12:33

本文选题：Caveolin-1　切入点：食管肿瘤　出处：《山东大学》2015年硕士论文　论文类型：学位论文

【摘要】：研究背景及目的食管鳞癌(ESCC)是世界上最常见的恶性肿瘤之一,其在中国的患病率和死亡率相对偏高。除环境危险因素吸烟、饮酒、饮用热茶外,有证据表明遗传因素,如单核苷酸多态性(SNPs),可能促进食管鳞癌的发生。Caveolin-1(CAV1)基因是Caveolin基因家族中主要的成员,其在肿瘤的发生、发展及转移过程中发挥重要的作用。在食管鳞癌组织中,CAV1表达水平升高与ESCC的浸润深度、淋巴结转移和预后密切相关。近期有研究表明,CAV1基因的单核苷酸多态性与肿瘤有关。本研究旨在探讨CAV1基因多态性位点C239A(rs 1997623)、G14713A (rs3807987)、G21985A (rs12672038)、T29107A (rs7804372)的基因多态性与食管鳞癌易感性的关联。方法该病例-对照研究包括427例食管鳞癌患者和427例按性别、年龄(±1岁)频数匹配的正常对照者。每人抽取外周血5m1并提取基因组DNA。采用聚合酶链反应一限制性片段长度多态性法(polymerase chain reaction and restriction fragment length polymorphism, PCR-RFLP)检测CAV1基因多态位点C239A (rs1997623)、 G14713A(rs3807987)、G21985A(rs 12672038)、T29107A (rs7804372)的基因型。采用以贝叶斯分析方法为原理的PHASE软件构建单倍体型,并计算各基因多态性位点的单倍体型频率。采用条件Logistic回归模型分析基因多态性位点的基因型、等位基因及单倍型与食管鳞癌发病风险的相关性。根据病例组和对照组的年龄、性别、吸烟史、饮酒史进行分层分析,评估CAV1基因多态性位点G14713A和T29107A的基因型对食管鳞癌易感性的影响。结果病例组和对照组在年龄、吸烟、饮酒三方面的分布无统计学差异(P=0.893,P=0.154,P=0.101)；病例组G14713A位点的基因型AG和AA及等位基因A的频率显著高于对照组(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,病例组T29107A位点的基因型AA以及等位基因A明显低于对照组(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位点的基因型和等位基因频率在两组中的分布差异均无统计学意义(P0.05)。单倍型分析表明：单倍型CAAT和CAGT显著增加了食管鳞癌的发病风险(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),而单倍型CGGA降低了食管鳞癌的易感性(OR=0.176,95%CI=0.071-0.437,P0.00001).分层分析结果表明：多态性位点G14713A可同时增加男性(P=0.00344)、女性(P=0.00009)60岁(P=0.00013)、≥60岁(P=0.00021)、不吸烟及不饮酒(P0.00001,P=0.00003)个体的食管鳞癌发病风险,而多态性位点T29017A可同时降低女性(P=0.00013)、不吸烟(P=0.00140)和不饮酒(P=0.00027)个体罹患食管鳞癌的可能性。结论CAV1基因多态位点C239A.G14713A.G21985A.T29107A均具有多态性；G14713A和T29107A位点的多态性与食管鳞癌易感性相关,而C239A和G21985A位点的多态性与食管鳞癌易感性无关；单倍体型CAAT和CAGT是食管鳞癌的危险因素,而单倍体型CGGA是食管鳞癌的保护因素；多态位点G14713A和T29107A与食管鳞癌易感性的关联性在女性患者及不吸烟不饮酒的患者中更加显著；多态性位点G14713A和T29107A将成为有利于食管鳞癌的早期诊断、个体化治疗的有效遗传标记物。
[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.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.1

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