survivin基因启动子-625gc位点多态性与结直肠癌相关性研究

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1、中图分类号：R36硕士学位论文Survivin基因启动子-625G/C位点多态性与结直肠癌相关性研究院（系）、所基础医学院研究生姓名程序学科、专业病理学与病理生理学导师姓名孙兴旺教授二Ο一二年四月1目录1Survivin基因启动子-625G/C位点多态性与结直肠癌相关性研究„„11.1中文摘要„„„„„„„„„„„„„„„„„„„„„„„„„11.2英文摘要„„„„„„„„„„„„„„„„„„„„„„„„„51.3前言„„„„„„„„„„„„„„„„„„„„„„„„„„„91.4材料与方法„„„„„„„„„„„„„„„„„„„„„

2、„„„131.5结果„„„„„„„„„„„„„„„„„„„„„„„„„„„241.6讨论„„„„„„„„„„„„„„„„„„„„„„„„„„„311.7结论„„„„„„„„„„„„„„„„„„„„„„„„„„„381.8参考文献„„„„„„„„„„„„„„„„„„„„„„„„„391.9英汉缩略词对照表„„„„„„„„„„„„„„„„„„„„„452致谢„„„„„„„„„„„„„„„„„„„„„„„„„„„463Glypican-3的研究进展（综述）„„„„„„„„„„„„„„„472Survivin基因启动子-625G/C位点多

3、态性与结直肠癌相关性研究摘要目的：通过检测-625G/C多态位点在结直肠癌（CRC）人群及正常人群中的基因型频率和等位基因频率分布情况，探讨survivin启动子-625G/C位点多态性与CRC患病风险之间的关联；与CRC患病的临床病理学参数（肿瘤部位、肿瘤大小、大体类型、组织类型、浸润深度、分化程度、淋巴转移）的关系；与CRC患病的临床检测肿瘤标志物（CA19-9、CA72-4、AFP、CEA）的关系；与CRC患病血脂生化指标（LDL-C、TC）的关系。为进一步深入细致的了解和认识CRC发生、发展以及转移提供部分实验依据。方法：

4、随机选取2009年到2011年的四川省泸州医学院附属医院CRC确诊患者236例和健康人254例分为CRC组和对照组，抽取外周静脉血，采用“酚-氯仿法”提取血液单个核细胞DNA,设计survivin启动子区的-625G/C位点的错配引物，利用PCR-RFLP技术中的PCR-错配引物酶切法，以及琼脂糖凝胶电泳技术鉴定survivin启动子区的-625G/C位点基因型。对基因型进行哈代-温伯格平衡（Hardy-WeinbergEquilibriumHWE）2检验，验证选取的调查资料的可靠性。采用χ检验检测CRC组和对照组基因型频率、等位

5、基因频率之间分布差异。收集临床病理参数（肿瘤部位、肿瘤大小、大体类型、组织类型、分化程度、浸润深度、淋巴转移）、CRC患者术前初诊的临床检测肿瘤标志物（CA19-9、CA72-4、AFP、CEA）2以及血脂相关生化指标（LDL-C、TC）资料。采用χ检验分析CRC患2者survivin启动子区的-625G/C位点基因型与肿瘤标志物的相关性；采用χ检验分析CRC患者survivin启动子区的-625G/C位点基因型与肿瘤临床病3理学参数的关系；采用t检验分析基因型频率与临床肿瘤标志物及临床生化指标相关性。所有分析均采用SPSS19.

6、0软件进行，以P<0.05具有统计学意义。结果：CRC组和对照组在性别、年龄上匹配，分布无统计学差22异，P性别﹥0.05(χ性别=0.119，P性别=0.784，双侧)；P年龄﹥0.05(χ年龄=0.166，P年龄=0.748，双侧)。CRC组和对照组survivin启动子区的-625G/C位点基因型频率及等位基因频率均符合HWE平衡定律,CRC组P＞0.0522（χ=0.414，P=0.520）；对照组P＞0.05（χ=0.070，P=0.792）。CRC组和对照组-625G/C位点GG、GC+CC各基因型频率总体分布有显著性

7、差异，2P＜0.05（χ=5.393，P=0.004，双侧）；G、C等位基因频率总体分布有显著2性差异，P＜0.05（χ=8.490，P=0.023，双侧）。CRC患者-625G/C位点GG、GC+CC各基因型频率在不同肿瘤部位（结肠、直肠）没有显著性差异，P2＞0.05(χ=0.633，P=0.426，双侧)；在不同肿瘤大小（≥3cm、<3cm）中没2有显著性差异，P＞0.05(χ=0.045，P=0.833，双侧)；在不同肿瘤大体类型2（溃疡型、隆起型）中没有显著性差异，P＞0.05(χ=0.017，P=0.896，双侧)；在

8、不同肿瘤组织类型（腺癌、粘液腺癌）没有显著性差异，P＞0.052(χ=0.058，P=0.810，双侧)；在不同肿瘤腺癌分化程度（高分化、中低分2化）没有显著性差异，P＞0.05(χ=1.199，P=0.274，双侧)；在不同肿瘤浸2润深度（未到全