外周血DNA FHIT、RASSF1A基因甲基化水平与非小细胞肺癌危险性分析

Promoter methylation of FHIT and RASSFIA in genomic DNA of peripheral blood and risk of non-small cell lung cancer

目的 观察外周血 DNA 脆性组氨酸三联体基因 （ FHIT ）、 RAS 相关结构域家族基因1A （ RASSF1A ）甲基化水平与非小细胞肺癌危险性的关系。方法 采用实时荧光定量 PCR 方法测定136 例非小细胞肺癌患者、 140 例肺良性疾病患者及 145 名正常对照者外周血 DNAFHIT 、 RASSF1A基因甲基化水平。结果 肺癌组、肺良性疾病组和正常对照组 FHIT 、 RASSF1A 基因启动子甲基化率比较,差异均有统计学意义 （χ2 值分别为 6.281 、 4.123 ,P 值均 〈0.05 ）。单因素 logistic 回归分析结果提示,性 别 对 患 肺 癌 的 危 险 性 无 影 响 （ OR =1.434 , P =0.377 ）, 年 龄、 吸 烟 史、 FHIT 、RASSF1A 甲基化率对患肺癌的危险性有影响 （ OR 值分别为 1.712 、 1.983 、 1.698 、 1.735 , P 值分别为 0.005 、 0.002 、 0.017 、 0.001 ）。多因素 logistic 回归分析结果表明,随着 FHIT 、 RASSF1A 甲基化水平升高,患肺癌的危险性均明显增加 （ OR 值分别为 1.767 、 1.367 , P 值分别为 0.002 、 0.016 ）。性别、高龄和吸烟史均可增加患肺癌的危险性 （ OR 值分别为 2.786 、 3.829 、 4.216 , P 值均为 0.000 ）。结论 外周血 DNAFHIT 、 RASSF1A 高甲基化水平与非小细胞肺癌相关,可作为肺癌临床诊断中重要的生物标志物。

Objective To observe the relationship of promoter methylation of fragile histidine triad gene （FHIT） and ras assotiation domain family 1A （RASSF1A） in genomic DNA of peripheral blood with risk of non small cell lung cancer. Methods Promoter methylation of FHIT and RASSF1A in genomic DNA of peripheral blood was measured by quantitative polymerase chain reaction among 136 patients with non-small cell lung cancer, 140 patients with lung benign diseases, and 145 healthy controls. Results There was statistically significant difference in methylation levels of FHIT and RASSF1A genes among lung cancer group, lung benign disease group, and control group （x^2=6. 281,4. 123, all P 〈0.05）. Single-factor non-conditional logistic regression analysis showed that gender had no risk impact on lung cancer （ OR = 1. 434, P = 0. 377）, while age, smoking and methylation levels of FHIT and RASSF1A genes promoted the development of lung cancer （OR =1.712,1.983,1.698,1.735, P =0.005,0.002, 0.017,0. 001, respectively）. Multiple factor non-conditional logistic regression analysis showed that the risk of lung cancer increased with methylation status of FHIT and RASSF1A genes （ OR = 1. 767, 1. 367, P=0.002, 0.016）, and the risk of lung cancer was increased with gender, age and smoking （ OR = 2. 786,3. 829,4. 216, respectively, all P 0. 000）. Conclusions The higher methylation levels of FHIT and RASSFIA genes may be associated with higher risk of non-small ceil lung cancer, and they can be used as clinic diagnosis marker for lung cancer.