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DNA修復(fù)通路基因多態(tài)性與宮頸癌同步放化療敏感性的關(guān)聯(lián)研究

發(fā)布時(shí)間:2018-06-03 13:19

  本文選題:宮頸癌 + DNA修復(fù)。 參考:《西北大學(xué)》2016年碩士論文


【摘要】:宮頸癌是一種常見(jiàn)的婦科惡性腫瘤,在發(fā)展中國(guó)家中,有較高的發(fā)病率和死亡率。目前晚期局部宮頸癌的主要治療手段是同步放化療(CCRT), CCRT與其它的傳統(tǒng)治療手段相比具有毒副作用更小,患者的生存期更長(zhǎng)等優(yōu)勢(shì)。但是由于不同個(gè)體之間遺傳差異,一部分患者表現(xiàn)出較低的應(yīng)答率。CCRT治療主要是通過(guò)誘導(dǎo)各種類型的DNA損傷,進(jìn)而引起細(xì)胞周期阻滯,并誘導(dǎo)細(xì)胞凋亡。CCRT會(huì)誘發(fā)DNA雙鏈斷裂,而DNA雙鏈斷裂主要是通過(guò)同源重組和非同源末端鏈接進(jìn)行修復(fù)的。當(dāng)腫瘤細(xì)胞可以高效的對(duì)CCRT誘導(dǎo)的DNA損傷進(jìn)行修復(fù),就會(huì)降低CCRT對(duì)腫瘤細(xì)胞的殺傷力。因此在放化療治療中,造成患者會(huì)對(duì)CCRT表現(xiàn)出低應(yīng)答,治療效果欠佳。有研究證實(shí),DNA修復(fù)通路中基因多態(tài)性與腫瘤患者的放化療敏感性密切相關(guān)。因此,本課題以DNA修復(fù)通路中SNPs作為研究對(duì)象,分析DNA修復(fù)通路基因多態(tài)性與宮頸癌患者放化療敏感性的相關(guān)性,旨在找到中國(guó)人群宮頸癌患者同步放化療敏感性的分子標(biāo)志物。本課題以72例宮頸癌組織樣本為研究對(duì)象,基于焦磷酸測(cè)序法對(duì)25個(gè)DNA修復(fù)基因的共29個(gè)SNP位點(diǎn)進(jìn)行檢測(cè),并將檢測(cè)結(jié)果與患者的臨床病理特征及放化療敏感性進(jìn)行關(guān)聯(lián)分析。結(jié)果表明,DNA修復(fù)基因EXO1-rs9350多態(tài)性與宮頸癌患者對(duì)CCRT應(yīng)答率顯著相關(guān)(odds ratio [OR],8.316; 95%CI,2.245-30.807; p=0.002)。 EXO1-rs9350可以作為獨(dú)立預(yù)測(cè)宮頸癌患者放化療敏感性的預(yù)測(cè)因子。
[Abstract]:Cervical cancer is a common gynecologic malignancy with high morbidity and mortality in developing countries. At present, the main treatment of advanced local cervical cancer is concurrent radiotherapy and chemotherapy. Compared with other traditional treatment, CCRT has less side effects and longer survival. However, because of the genetic differences among different individuals, some patients showed low response rate. CCRT treatment mainly induced various types of DNA damage, and then caused cell cycle arrest, and induced apoptosis. CCRT could induce DNA double strand break. DNA double strand breaks were repaired by homologous recombination and non-homologous terminal links. When tumor cells can efficiently repair DNA damage induced by CCRT, it will reduce the cytotoxicity of CCRT to tumor cells. Therefore, in radiotherapy and chemotherapy, patients will show a low response to CCRT, the treatment effect is not good. Some studies have confirmed that gene polymorphism in DNA repair pathway is closely related to chemosensitivity of tumor patients. Therefore, SNPs in DNA repair pathway was used as the research object to analyze the relationship between gene polymorphism of DNA repair pathway and radio-chemosensitivity in patients with cervical cancer. The aim of this study was to identify the molecular markers of chemosensitivity in cervical cancer patients in China. A total of 29 SNP loci of 25 DNA repair genes were detected by pyrosequencing in 72 cervical cancer tissue samples. The results were correlated with clinicopathological features and chemoradiotherapy sensitivity of patients. The results showed that the EXO1-rs9350 polymorphism of the repair gene was significantly associated with odds ratio [OR] 8.316; 95 CI2.245-30.807; p0.002; EXO1-rs9350 can be used as an independent predictor of chemoradiosensitivity in patients with cervical cancer.
【學(xué)位授予單位】:西北大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2016
【分類號(hào)】:R737.33

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 許義松;周文靜;祁曉麗;席佩;戴鵬高;;NHEJ信號(hào)通路關(guān)鍵基因mRNA表達(dá)與宮頸鱗癌同步放化療敏感性的關(guān)系[J];西北大學(xué)學(xué)報(bào)(自然科學(xué)版);2015年05期

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