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DNA修复通路基因多态性与宫颈癌同步放化疗敏感性的关联研究

发布时间:2018-06-03 13:19

  本文选题:宫颈癌 + DNA修复 ; 参考:《西北大学》2016年硕士论文


【摘要】:宫颈癌是一种常见的妇科恶性肿瘤,在发展中国家中,有较高的发病率和死亡率。目前晚期局部宫颈癌的主要治疗手段是同步放化疗(CCRT), CCRT与其它的传统治疗手段相比具有毒副作用更小,患者的生存期更长等优势。但是由于不同个体之间遗传差异,一部分患者表现出较低的应答率。CCRT治疗主要是通过诱导各种类型的DNA损伤,进而引起细胞周期阻滞,并诱导细胞凋亡。CCRT会诱发DNA双链断裂,而DNA双链断裂主要是通过同源重组和非同源末端链接进行修复的。当肿瘤细胞可以高效的对CCRT诱导的DNA损伤进行修复,就会降低CCRT对肿瘤细胞的杀伤力。因此在放化疗治疗中,造成患者会对CCRT表现出低应答,治疗效果欠佳。有研究证实,DNA修复通路中基因多态性与肿瘤患者的放化疗敏感性密切相关。因此,本课题以DNA修复通路中SNPs作为研究对象,分析DNA修复通路基因多态性与宫颈癌患者放化疗敏感性的相关性,旨在找到中国人群宫颈癌患者同步放化疗敏感性的分子标志物。本课题以72例宫颈癌组织样本为研究对象,基于焦磷酸测序法对25个DNA修复基因的共29个SNP位点进行检测,并将检测结果与患者的临床病理特征及放化疗敏感性进行关联分析。结果表明,DNA修复基因EXO1-rs9350多态性与宫颈癌患者对CCRT应答率显著相关(odds ratio [OR],8.316; 95%CI,2.245-30.807; p=0.002)。 EXO1-rs9350可以作为独立预测宫颈癌患者放化疗敏感性的预测因子。
[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.
【学位授予单位】:西北大学
【学位级别】:硕士
【学位授予年份】:2016
【分类号】:R737.33

【参考文献】

相关期刊论文 前1条

1 许义松;周文静;祁晓丽;席佩;戴鹏高;;NHEJ信号通路关键基因mRNA表达与宫颈鳞癌同步放化疗敏感性的关系[J];西北大学学报(自然科学版);2015年05期



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