XRCC5、XRCC6单核苷酸多态性与乳头状甲状腺癌BRAF基因突变相关性研究

发布时间：2018-06-12 13:56

本文选题：甲状腺乳头状癌 + BRAF　；参考：《滨州医学院》2016年硕士论文

【摘要】：背景:最近的研究结果表明,国内甲状腺癌的发病率呈不断攀升的态势。其发病率由1/10万上升至3-4/10万。甲状腺恶性肿瘤中最为常见的病理类型是乳头状甲状腺癌(PTC)(约占甲状腺恶性肿瘤比例的80%)。环境与遗传因素作为肿瘤致病因素的两方面互为增强。一方面电离辐射作为甲状腺癌较为明确的环境致病因素引起的DNA双链断裂增加了甲状腺癌的易感性;另一方面参与甲状腺癌发生与发展的遗传学分子机制主要是基因的点突变和染色体重排,其中癌基因BRAF V600E的点突变研究较为广泛。此外,修复DSB基因的单核苷酸多态性(single nucleotide polymorphism,SNP)作为甲状腺癌遗传易感因素新的研究课题备受关注。DSB修复基因的单核苷酸多态性(SNP)对PTC的诊断、治疗、肿瘤良恶性评估以及预后监测均具有积极的指导作用。分析参与DSB修复路径中修复基因的单核苷酸多态性与BRAF突变的关联对进一步探索和揭示乳头状甲状腺癌的发病机制具有重要意义,为此我们选取XRCC5、XRCC6作为修复基因多态性研究对象并探查其多态性与BRAF突变有无相关性。目的:寻找与BRAF突变显著相关的修复基因的SNPs,以期为PTC的诊疗提供新的分子靶点,同时为临床预测BRAF突变风险,为甲状腺乳头状癌的诊治及预后监测提供新的分子标志物。方法:采用以医院临床标本为基础的病例-病例研究,拟应用分子流行病学的方法,利用已有的标本提取DNA,借助PCR技术进行基因分型,设计并分析乳头状甲状腺癌患者中XRCC5、XRCC6基因多态性在BRAF突变型与野生型之间的分布情况。结果:1. XRCC5基因rs2160981位点的基因型在BRAF野生型和突变型两个分组间存在明显差异(X2: 9.267; P: 0.008),具有统计学意义;同时rs2160981位点的等位基因频率在两组间的差异也具有统计学意义(X2: 7.262; P: 0.009)。2. XRCC6基因rs132771位点基因型在BRAF野生型和突变型两组间的差异具有统计学意义(X2: 7.067; P: 0.008),该位点的等位基因频率在BRAF野生型和突变型两组间的差异具有统计学意义(X2: 6.563; P: 0.001)。结论:乳头状甲状腺癌(PTC)患者非同源修复通路中XRCC5、XRCC6基因的单核苷酸多态性(SNPs)与BRAF突变具有相关性。
[Abstract]:Background: recent studies have shown that the incidence of thyroid cancer is increasing in China. Its incidence has risen from 1 / 100, 000 to 3-4 / 100, 000. The most common pathological type of thyroid neoplasms is papillary thyroid carcinoma (PTC) (about 80% of thyroid neoplasms). Environmental and genetic factors are mutually reinforcing as tumor pathogenic factors. On the one hand, the DNA double strand breakage caused by ionizing radiation as a definite environmental pathogenic factor of thyroid cancer increased the susceptibility of thyroid carcinoma. On the other hand, point mutation and chromosome rearrangement are the main molecular mechanisms involved in the genesis and development of thyroid carcinoma, among which the point mutation of BRAF V600E is widely studied. In addition, single nucleotide polymorphisms (SNPs) that repair the DSBs gene as a new genetic susceptibility factor for thyroid cancer have attracted much attention in the diagnosis and treatment of thyroid cancer, including the single nucleotide polymorphisms (SNPs) of the DSB-repair gene (SNPs), and the clinical significance of the single nucleotide polymorphisms (SNPs) in the diagnosis and treatment of thyroid carcinomas. Both benign and malignant tumor evaluation and prognosis monitoring have a positive guiding role. It is important to analyze the association between the single nucleotide polymorphism of repair gene involved in the repair pathway of DSB and the BRAF mutation in order to further explore and reveal the pathogenesis of papillary thyroid carcinoma. Therefore, we selected XRCC5 and XRCC6 as repair gene polymorphisms and investigated their association with BRAF mutation. Objective: to search for the repair gene SNPsrelated to BRAF mutation in order to provide a new molecular target for the diagnosis and treatment of PTC, to predict the risk of BRAF mutation in clinic, and to provide a new molecular marker for the diagnosis, treatment and prognosis monitoring of papillary thyroid carcinoma. Methods: a case-case study based on clinical specimens was used. The method of molecular epidemiology was used to extract DNA from existing samples and genotyping was carried out by PCR. To design and analyze the distribution of XRCC5 and XRCC6 gene polymorphism between BRAF mutation and wild type in patients with papillary thyroid carcinoma. The result is 1: 1. The genotypes of rs2160981 locus of XRCC5 gene were significantly different between wild type and mutant group X2: 9.267; P: 0.008, with statistical significance, and the allele frequency of rs2160981 locus was also significantly different between the two groups (X2: 7.262; P: 0.009, 0.62; P0. 009; P: 0. 009; P: 0. 009, P: 0. 009, P: 0. 009, P: 0. 009, P: 0. 009). The rs132771 genotype of XRCC6 gene was significantly different between wild type and mutant group (X2: 7.067; P: 0.008). The allele frequency of XRCC6 gene was significantly different between wild type and mutant group (X2: 6.563; P: 0.001). Conclusion: the single nucleotide polymorphism (SNPs) of XRCC5 and XRCC6 gene in non-homologous repair pathway in patients with papillary thyroid carcinoma (PTC) is associated with BRAF mutation.
【学位授予单位】：滨州医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R736.1

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