本文選題：甲狀腺乳頭狀癌 + BRAF��； 參考：《濱州醫(yī)學(xué)院》2016年碩士論文

【摘要】：背景:最近的研究結(jié)果表明,國內(nèi)甲狀腺癌的發(fā)病率呈不斷攀升的態(tài)勢。其發(fā)病率由1/10萬上升至3-4/10萬。甲狀腺惡性腫瘤中最為常見的病理類型是乳頭狀甲狀腺癌(PTC)(約占甲狀腺惡性腫瘤比例的80%)。環(huán)境與遺傳因素作為腫瘤致病因素的兩方面互為增強。一方面電離輻射作為甲狀腺癌較為明確的環(huán)境致病因素引起的DNA雙鏈斷裂增加了甲狀腺癌的易感性;另一方面參與甲狀腺癌發(fā)生與發(fā)展的遺傳學(xué)分子機(jī)制主要是基因的點突變和染色體重排,其中癌基因BRAF V600E的點突變研究較為廣泛。此外,修復(fù)DSB基因的單核苷酸多態(tài)性(single nucleotide polymorphism,SNP)作為甲狀腺癌遺傳易感因素新的研究課題備受關(guān)注。DSB修復(fù)基因的單核苷酸多態(tài)性(SNP)對PTC的診斷、治療、腫瘤良惡性評估以及預(yù)后監(jiān)測均具有積極的指導(dǎo)作用。分析參與DSB修復(fù)路徑中修復(fù)基因的單核苷酸多態(tài)性與BRAF突變的關(guān)聯(lián)對進(jìn)一步探索和揭示乳頭狀甲狀腺癌的發(fā)病機(jī)制具有重要意義,為此我們選取XRCC5、XRCC6作為修復(fù)基因多態(tài)性研究對象并探查其多態(tài)性與BRAF突變有無相關(guān)性。目的:尋找與BRAF突變顯著相關(guān)的修復(fù)基因的SNPs,以期為PTC的診療提供新的分子靶點,同時為臨床預(yù)測BRAF突變風(fēng)險,為甲狀腺乳頭狀癌的診治及預(yù)后監(jiān)測提供新的分子標(biāo)志物。方法:采用以醫(yī)院臨床標(biāo)本為基礎(chǔ)的病例-病例研究,擬應(yīng)用分子流行病學(xué)的方法,利用已有的標(biāo)本提取DNA,借助PCR技術(shù)進(jìn)行基因分型,設(shè)計并分析乳頭狀甲狀腺癌患者中XRCC5、XRCC6基因多態(tài)性在BRAF突變型與野生型之間的分布情況。結(jié)果:1. XRCC5基因rs2160981位點的基因型在BRAF野生型和突變型兩個分組間存在明顯差異(X2: 9.267; P: 0.008),具有統(tǒng)計學(xué)意義;同時rs2160981位點的等位基因頻率在兩組間的差異也具有統(tǒng)計學(xué)意義(X2: 7.262; P: 0.009)。2. XRCC6基因rs132771位點基因型在BRAF野生型和突變型兩組間的差異具有統(tǒng)計學(xué)意義(X2: 7.067; P: 0.008),該位點的等位基因頻率在BRAF野生型和突變型兩組間的差異具有統(tǒng)計學(xué)意義(X2: 6.563; P: 0.001)。結(jié)論:乳頭狀甲狀腺癌(PTC)患者非同源修復(fù)通路中XRCC5、XRCC6基因的單核苷酸多態(tài)性(SNPs)與BRAF突變具有相關(guān)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.
【學(xué)位授予單位】：濱州醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R736.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 李瑩瑩;宋西成;;DNA雙鏈斷裂修復(fù)基因的單核苷酸多態(tài)性與甲狀腺癌的研究進(jìn)展[J];山東大學(xué)耳鼻喉眼學(xué)報;2016年02期

2 易文君;鐘德s，

本文編號：2009903