p16和FHIT基因启动子甲基化与肺癌的关系  

Relationship of methylation of p16 and FHIT gene promoters with lung cancer

作　　者：周安燕[1] 田蕊[1] 吴拥军[1] 邝红萍[1] 陆青[1] 王静[1] 

机构地区：[1]郑州大学第一附属医院呼吸内科,450052

出　　处：《国际呼吸杂志》2014年第10期744-748,共5页International Journal of Respiration

基　　金：国家自然科学基金资助项目（30972457）;河南省重大科技攻关项目（112102310102）

摘　　要：目的 探讨外周血p16和FHIT启动子区甲基化与肺癌的发生关系.方法 应用实时荧光定量甲基化特异性PCR方法检测180例肺癌患者和180名健康对照者外周血p16、FHIT基因启动子序列的甲基化率,并对比分析两者的甲基化水平在肺癌患者和健康人群中存在的差异.探讨各个临床病理特征是否对两者的基因启动子的甲基化率产生影响,分析两者的甲基化水平以及性别、年龄和吸烟史等因素与发生肺癌的危险相关性.结果 肺癌组p16和FHIT基因的甲基化水平高于对照组（p16：Z=-2.560,P=0.010;FHIT：Z=-2.797,P=0.005）.p16和FHIT基因的甲基化水平与性别、年龄、吸烟史、肺癌的组织类型及临床分期均无明显关联（p16：Z=-1.121,P=0.262,Z=-0.304,P=0.761,Z=-0.082,P=0.935,x2=0.582,P=0.748,Z=-1.605,P=0.108;FHIT：Z=-0.169,P =0.886,Z=-0.411,P=0.681,Z=-1.095,P=0.273,x2=2.97,P=0.227,Z=-1.189,P=0.234）.单因素logistic回归分析结果显示性别对肺癌的危险性无影响（OR=1.274,P=0.297）,年龄、吸烟、p16和FHIT甲基化水平对肺癌的危险性有影响（OR值分别为1.952、1.888、1.598、1.830,P值分别为0.002、0.003、0.027、0.005）.多因素logistic回归分析结果显示FHIT随着其甲基化水平升高,患肺癌的危险性明显增加（OR =1.867,P=0.006）;p16随着其甲基化水平升高,患肺癌的危险性增加可能性很大（OR=1.477,P=0.086）.联合2个基因甲基化检测可提高对肺癌诊断的价值（AUC=0.832,P＜0.01）.结论 外周血p16和FHIT基因启动子甲基化和肺癌有关;联合2个基因检测比单个基因检测对肺癌诊断价值高;p16和FHIT基因启动子甲基化水平检测有望成为肺癌筛查、早期诊断的指标.Objective To investigate the relationship between detection of promoters methylation status of cancer suppressor genes such as the cell-cycle inhibitor gene CDKN2A （p16）,fragile histidine triad （FHIT） genes in peripheral blood and the development of lung cancer.Methods Real-time quantitative methylation specific PCR was used to detect the status of p16 and FHIT gene promoters methylation in peripheral blood collected from 180 lung cancer patients and 180 normal controls.The differences between lung cancer group and control group in methylation status were analyzed and compared.The effect of age,gender,smoking,histological type and clinical stage on the methylation of the referred two gene promoters were discussed,and the relationship between lung cancer and risk factors,such as age,gender,smoking and methylation level of the referred gene promoters was studied.Results There were statistically significant differences in methylation levels between p16 and FHIT genes （p16：Z =-2.560,P =0.010;FHIT：Z =-2.797,P =0.005）.These two genes were more highly methylated in lung cancer group compared with control group.The methylation levels of p16 and FHIT genes had no obvious relevance with gender,age,smoking history,histological type and clinical stage （p16：Z =-1.121,P=0.262,Z=-0.304,P =0.761,Z =-0.082,P=0.935,x2=0.582,P=0.748,Z=-1.605,P=0.108;FHIT：Z =-0.169,P =0.886,Z =-0.411,P =0.681,Z =-1.095,P =0.273,x2 =2.97,P =0.227,Z =-1.189,P =0.234）.Single-factor non-conditional logistic regression analysis showed that gender had no risk impact on lung cancer （OR =1.274,P =0.297）,while age,smoking and methylation levels of p16 and FHIT genes promoted the development of lung cancer （OR =1.952,1.888,1.598,1.830,P =0.002,0.003,0.027,0.005,respectively）.Multiple-factor nonconditional logistic regression analysis showed that the risk of lung cancer increased with methylation status of FHIT gene （OR =1.867,P =0.006）,and the risk of lung cancer was possibly increased while the methylation level of p16 gen

关 键 词：P16基因 FHIT基因 甲基化 肺癌 

分 类 号：R734.2[医药卫生—肿瘤]