P16基因甲基化和GSTM1基因多态性与非小细胞肺癌易感性研究  

STUDY ON THE METHYLATION OF P16 GENE AND GENETIC POLYMORPHISM OF GSTM1 GENE RELATED WITH SUSCEPTIBILITY TO NON-SMALL CELL LUNG CANCER

作　　者：汪亚松[1] 金永堂[1] 薛绍礼[1] 于在诚[2] 徐迎春[1] 刘晓[2] 田敏华[3] 陶文虎[2] 孔云明[1] 侯勇[1] 

机构地区：[1]安徽医科大学公共卫生学院,合肥230032 [2]安徽医科大学第一附属医院胸外科 [3]安徽省合肥市第一人民医院体检中心

出　　处：《现代预防医学》2007年第7期1207-1209,1212,共4页Modern Preventive Medicine

基　　金：国家自然科学基金资助项目(NO.30471427)

摘　　要：[目的]研究P16基因甲基化、谷胱甘肽硫转移酶M1基因(GSTM1)多态性和环境暴露与非小细胞肺癌(NSCLC)的关系。[方法]采用病例对照研究方法选择47例NSCLC患者和94例对照,用甲基化特异性PCR(MSP)检测P16基因甲基化,GSTM1基因多态性用限制性片断长度多态性PCR(PCR-RFLP)测定。[结果]肺癌组接触粉尘、毒物频率高于对照组(P﹤0.01),食用蔬菜水果、饮用消毒水频率肺癌组低于对照组(P﹤0.01);肺癌组织甲基化率44.7%,高于癌旁组织的17%(P﹤0.01),甲基化和吸烟高度相关(P﹤0.01);GSTM1多态性分布无统计学意义(P﹥0.05),粉尘接触、吸烟和GSTM1缺陷型有协同作用,P16甲基化和GSTM1多态性关系不明显。[结论]接触粉尘、毒物明显增加NSCLC危险性,食用蔬菜水果和消毒水降低NSCLC危险性;吸烟致P16基因甲基化参与NSCLC的形成,粉尘、吸烟可能增加GSTM1缺失型患NSCLC危险性,未发现P16甲基化和GSTM1多态性有交互作用。[ Objective] To study the relationship among the genetic polymorphism of glutathione S- transferase M1 （GSTM1） , methylation of P16 gene, environment exposure and susceptibility to non-small cell lung cancer （NSCLC） . [Methods] The case-control study was conducted among 47 NSCLC cases and 94 controls, methylation of P16 gene was tested by methylation-specific PCR （MSP）, GSTM1 gene genetic polymorphisois were genotyped with method of polymerase chain reaction-restriction fragment length polymorphism （PCR - RFLP） . [Results] There was a high frequency of dust anti toxicant exposure in cases than in controls （P 〈 0.01 ） . By contrary, the frequency of eating vegetables, fruits and d,＇inking sanitized water frequently was lower in cases. In cancer tissues, the frequency of P16 methylation was 44.7%, which was significantly higher than that in the nomalignant tissue. （ 17%, P 〈 0.01 ） . Methylation of P16 significantly conelated with smoking （P 〈 0.01 ） . There was no statistical difference of GSTM1 null genotype frequency between cases and controls （P 〉 0.05 ） . There was a synergistic interaction between dust and tobacco exposure with GSTM1 null genotype, but methylation of P16 did not correlate with polymorphism of GSTM1. [Conclusion] This study revealed that dust and toxicant exposure increase the risk of NSCLC. Consumption of vegetables, fruits, and sanitized water frequently is associated with the decreased risk of NSCLC. Methylation of P16 gene owing to smoking is involved in the progress of NSCLC, and maybe there is an elevated risk of NSCLC in GSTM1 null genotype with exposure to dust and tobacco. This study did not reveal the interaction between polymorphism of GSTM1 and methylation of P16 in NSCLC.

关 键 词：P16 谷胱甘肽硫转移酶M1(GSTM1) 甲基化 基因多态性 非小细胞肺癌 

分 类 号：R734.202[医药卫生—肿瘤]