GSTM1、GSTT1基因缺失与肺癌易感性的关系  

Relationship between deletion of GSTM1,GSTT1 genes and susceptibility to lung cancer

作　　者：姚武[1] 王娜[1] 吴拥军[1] 吴逸明[1] 

机构地区：[1]郑州大学公共卫生学院劳动卫生与卫生毒理学教研室,郑州450052

出　　处：《中国公共卫生》2006年第9期1070-1072,共3页Chinese Journal of Public Health

基　　金：河南省自然科学基金项目(0111021400);"211工程"重点学科研究项目(200330164)

摘　　要：目的探讨谷胱苷肽S转移酶M1（GSTM1）、谷胱苷肽S转移酶T1（GSTT1）基因缺失与肺癌发病之间的关系及其与P16表达降低的相关性在肺癌发生中的作用。方法采用PCR技术检测77例肺癌患者和107例健康对照人群中GSTM1、GSTT1基因缺失的频率，以十二烷基磺酸钠（SDS）-聚丙烯酰胺凝胶电泳及蛋白印迹（WeStern—blot）技术测定P16蛋白在正常组织中的表达。结果病例组GSTM1基因缺失频率为58．4％，显著高于对照组缺失频率为42．1％（X^2=4．811，P=0．028），危险度分析OR=1．938，95％CI=1．070～3．509；病例组GSTT1基因缺失频率为57．1％，接近对照组50．5％缺失频率的水平（X^2=0．802，P=0．371）。联合分析表明，2种基因在肺癌发生中具有协同作用。GSTM1空白基因型与GSTM1非空白基因型个体相比、GSTM1／GSTT1联合空白基因型与其他联合多态基因型相比P16表达水平降低，差异有统计学意义（P〈0．05）。结论GSTM1基因缺失或GSTM1、GSTT1基因联合缺失在肺癌患者中发生频率增高，可增加个体患肺癌的易感性；GSTM1基因缺失及GSTM1／GSTT1联合缺失可能与抑癌基因p16的蛋白表达减低有关。Objective To study the relationship between the deletion of glutathione S transferase M1 （GSTM1）, glutathione S transferase T1 （GSTT1） and susceptibility to lung cancer and its mechanism, Methods Using the method of PCR to detect the genotypes of GSTM1 and GSTT1 in 77 lung cancer patients and 107 healthy people, Using SDS - PAGE and Western - blot to detect the expression of P16 protein in normal lung tissue. Results There were 58.4 % （45/77） patients with GSTM1 null genotype in all eases and 42.1% （45/107） persons with GSTM1 null genotype in the healthy people, and there was significant difference between the two groups （X^2 = 4. 811, P = 0. 028）, and its OR was 1. 938 （95 % CI = 1. 095 -3.581） ;There were 57.1% （44/77） patients with GSTT1 null genotype in all eases and 50.5% （54/107） persons with GSTT1 null genotype in the healthy people, and there wasn＇t significant difference between the two groups （X^2 = 0. 802, P = 0. 371） ;There were 26 eases with GSTM1 null/GSTT1 null genotype in patients which was significantly higher than those in the healthy people, and its OR was 2.451 （95 % CI = 1. 067 -- 5. 633）. There was significant difference on the levels of P16 protein between individuals with GSTM1 null genotype and those with GSTM1 non - null genotype as well as the group of GSTM1/GSTT1 combined null genotype and those of GSTM1/GSTT1 combined positive （P 〈 0.05）. Conclusion GSTM1 null genotype and GSTM1/GSTT1 combined null genotype laid in much more lung cancer patients than healthy people, and it could highly increase the risk of lung cancer occurrence. The deletion of GSTM1 gene and GSTM1/GSTT1 combined null genotype were related to the low expression of P16 protein.

关 键 词：肺癌 遗传易感性 谷胱苷肽S转移酶M1(GSTM1) 谷胱苷肽S转移酶T1(GSTT1) P16蛋白 

分 类 号：R734.2[医药卫生—肿瘤]