多个抑癌基因启动子区域CpG岛异常甲基化与非小细胞肺癌关系及临床意义的研究  

Association of Abnormal Methylation of CpG Islands in Promoter Domains of Multiple Tumor Suppressor Genes with Non-Small Cell Lung Cancer

作　　者：金永堂[1] 徐鹤云[2] 张晨烨[1] 张虎[2] 薛绍礼[3] 于在诚[4] 徐迎春[5] 

机构地区：[1]浙江大学医学部公共卫生学院环境医学系,杭州市310058 [2]浙江大学附属邵逸夫医院胸心外科 [3]安徽医科大学基础医学院 [4]安徽医科大学附属第一医院胸心外科 [5]浙江大学医学部药学院

出　　处：《中国肿瘤临床》2010年第19期1109-1114,共6页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:30471427);浙江省自然科学基金资助(编号:R207067)~~

摘　　要：目的:分析多个抑癌基因启动子区域CpG岛异常甲基化与非小细胞肺癌关系。方法:收集原发性非小细胞肺癌患者肺癌组织与癌旁正常组织,提取DNA并利用甲基化特异PCR(MSP)方法进行抑癌基因甲基化检测,对资料进行Logistic回归分析。结果:对94例肺癌患者资料进行的分析结果表明,91.49%肺癌患者肺癌组织中抑癌基因发生了甲基化,明显高于相应的癌旁正常组织(40.43%)(P<0.01)。其中p16^(INK4a)、DAPK、MGMT、TIMP-3和RARβ基因的甲基化频率分别是41.49%、50.00%、17.02%、24.47%和68.09%,比癌旁正常组织高且具有统计学意义。抑癌基因甲基化对肺鳞癌、中央型肺癌和临床Ⅲ期及以上期肺癌的影响相对比较大,并随着甲基化指数的增加而显著增加。吸烟显著增加抑癌基因甲基化,尤其是p16^(INK4a)和DAPK基因甲基化,分别是不吸烟者的21.714倍和15.268倍(P<0.01)。而且,吸烟时间或吸烟指数与抑癌基因甲基化之间显示出剂量-反应关系。结论:吸烟增加抑癌基因甲基化的危险性,肺癌发病与多个抑癌基因甲基化密切相关。Objective： To analyze the association of abnormal methylation of CpG islands in the promoter domain of multiple tumor suppressor genes with non-small cell lung cancer. Methods： Methylation specific PCR was used to detect methylation of tumor suppressor genes （TSG） and the data were analyzed by logistic regression analysis. Results： The methylation data of 94 lung cancer cases were used in this study. The analysis revealed promoter domain methylation in more than one TSG in 91.49% of lung cancer tissue samples （P〈0.01）. Frequencies of promoter methylation in P161NK4a, DAPK, MGMT, TIMP-3 and RARI3 in lung cancer tissue were 41.49%, 50.00%, 17.02%, 24.47% and 68.09%, respectively, with a significant difference from those in normal lung tissue. The effect of TSG promoter methytation on squamous cell cancer, central lung cancer, and stage Ⅲ or more was increased as the methylation index （MI） increased. Smoking increased the risk of p161NK4a and DAPK methytation by OR of 21.714 and 15.268 （P〈0.01）, respectively. There was a dose-re- sponse relationship between smoking history and methylation of TSG. Conclusion： Smoking is an important risk factor for methylation of TSG and the methylation of multiple TSG plays a key role in the pathogenesis of lung cancer.

关 键 词：非小细胞肺癌 抑癌基因 甲基化 

分 类 号：R734.2[医药卫生—肿瘤]