尿苷二磷酸葡萄糖醛基转移酶1A7UGT1A7基因多态性和原发性肝癌易感性研究.pdf

目 录 一、摘要 1．中文论著摘要··············-··············-···················l 2．英文论著摘要·················································5 二、英文缩略语······················································7 三、论文 1。．肖f言·························································8． 日U舌。。。。。。。。’。。‘。。。。。。。。。。。。。。。‘‘‘。。。。。。。。。‘‘。。。。‘。’。。。。。。。‘。子 2．实验材料与方法··············································10 3．实验结果····················································14 4．讨论························································19 5．结论························································22 四、本研究创新性自我评价···········································23 五、参考文献·······················································24 六、附录 1．综述························································28 2．在学期间科研成绩············································37 3．致谢························································38 4．个人简介····················································39 ·中文论著摘要· 态性与原发性肝癌易感性的研究 莉 青 Carcinoma，PHC)是世界范围内常见的恶性肿 原发性肝癌(PrimaryHepatic 瘤之一，发病居所有恶性肿瘤的第六位，死亡居所有肿瘤死因的第三位。这种状 况在我国更加严峻，全世界55％的新发肝癌病例在我国，我国每年有35万人死于 肝癌，居所有恶性肿瘤死因的第二位。以往研究表明，肝癌的发生与多种因素有 关，包括乙型和丙型肝炎病毒感染，肝硬化，饮酒，黄曲霉毒素暴露等。除了环 境因素外，肝癌的发病还与个体对危险因素的敏感性有关。肿瘤相关基因的单核 苷酸多态导致的编码蛋白活性的差异被认为是个体敏感性的重要原因。 源性和外源性物质在体内进行II相生物转化时最重要的一种酶，催化多种外源性 和内源性化学物进行葡萄糖醛酸结合反应，将亲脂性的底物与葡糖醛酸结合转变 为极性较大的亲水性化合物，从而易于随尿、胆汁和粪便排出体外。UGTlA7是 UGT家族的成员之一，可以催化结合苯并芘等致癌物。近年来研究发现，UGTlA7 基因序列存在多态性，催化活性低的UGTlA7突变基因型与结直肠癌，肺癌，胰 腺癌等恶性肿瘤的易感性有关。在UGTlA7与原发性肝癌关系的研究中，各国研 究者结论不一，争议很大。而相关报道在中国较少，仅在台湾地区Tseng等人做 过相关研究。 本研究拟采用病例对照的设计方法，分析原发性肝癌组和对照组的UGTlA7 探讨中国东北人群UGTlA7基因多态与肝癌发病危险性的关系，以及UGTlA7 多态与肝癌其他相关因素的潜在交互作用，为肝癌的防治提供相关依据。 实验对象与方法 肝癌患者为病例组，用频数匹配的方法选择同期在体检中心体检的同性别、年龄士5 岁的136例非肿瘤患者为对照。收集所有研究对象的静脉血，人口学及相关因素 的资料信息。 c