eIF3a 2554G＞A基因多态性对肺癌患者铂类药物化疗敏感性的影响  

Impact of eIF3a 2554G>A genetic polymorphism on clinical sensitivity to platin-based chemotherapy in patients with lung cancer

作　　者：韩丽芳[1,2] 徐潇静[1] 沈杰[1] 裴奇[1] 符健[2] 周宏灏[1] 刘昭前[1] 

机构地区：[1]中南大学临床药理研究所遗传药理学湖南省重点实验室,湖南长沙410078 [2]海南省药物安全性评价研究中心海南医学院实验动物中心,海南海口571101

出　　处：《肿瘤药学》2011年第1期40-47,共8页Anti-Tumor Pharmacy

基　　金：国家自然科学基金项目(NO:30873089);湖南省自然科学基金重点项目(NO:08JJ3058);湖南省"芙蓉学者计划"特聘教授基金(湘教通[2006]312号)

摘　　要：目的 eIF3a在基因转录和翻译过程中起重要的调控作用,近年来研究发现eIF3a蛋白在肺癌组织中具有高表达本研究检测eIF3a基因2554G7A此位点的突变,研究这些突变与肺癌发生的易感性以及与肺癌患者化疗药物敏感性的关系。方法在湘雅医院收集肺癌患者和健康对照者血液标本用半巢式聚合酶链式反应连接的限制性片段长度多态性分析法对16号外显子的2554G>A进行分型,分析该基因多态性与肺癌易感性及肺癌患者对铂类药物化疗敏感性的相关性。结果 eIF3a 2554G>A突变在肺癌中的突变频率为10.9%,其中鳞癌突变频率为10.9%,腺癌为5.9%,小细胞癌为13.4%;健康人群中突变频率为15.3%在肺癌患者中,eIF3a 2554G>A三种基因型GG、GA和AA的频率分别为78.8%、20.6%和0.6%而健康对照者中,GG、GA和AA三种基因型的频率分别为72.9%、23.5%和3.5%。经非条件logistic回归平衡了性别、年龄和吸烟史后,GA、AA、GA+AA基因型患肺癌的危险性与GG基因型相比均无统计学意义,相对于GG基因型,GA型惠肺癌(OR=0.83,95%CI:0.49～1.41),AA型患肺癌(OR=0.18,95%CI:0.02～1.59),GA+AA基因型(OR=0.76,95%CI:0.45～1.27)。小细胞肺癌组GG基因型患者的化疗有效率低于GA基因型(65.0%vs75.0%),而非小细胞肺癌组GG基因型患者的化疗有效率高于GA+AA基因型(24.3%vs16.7%)结论eIF3a 2554G>A基因多态性与肺癌的发生无明显相关性在小细胞肺癌和非小细胞肺癌中,eIF3a 2554G>A不同基因型的个体具有不同的铂类化疗疗效。Objective elF3a plays an essential role in the regulation of initiation of mRNA transicripfion and protein translation in mammalian cells. Recent studies showed that eIF3a protein is overexpressed in lung cancer tissues. The aims of this study were to explore whether eIF3a 2554G〉A genetic polymorphism is associated with the susceptibility of lung cancer development and clinical responses to platinum-based chemotherapy in patients with lung cancer. Method Blood samples in all subjects werecollected from the Xiangya hospital of Central South University, Changsha, Hunan Province, P. R. China. The genotyping analysis of eIF3a 2554G〉A were determined by hemi-nested polymerase chain reaction restriction fragment length polymophism （PCR-RFLP）. Results The allele frequencies of elF3a 2554G〉A in healthy control, lung cancer, small cell lung cancer, squamous cell carcinoma, and adenocarcinoma were 15.3%, 10.9%, 15.7%, 13.4%, and 6.6%, respectively. The frequencies of elF3a 2554 GG, GA and AA in patients with lung cancer were 78.8%, 20.6% and 0.6% respectively. The frequencies of elF3a 2554 GG, GA and AA in healthy control were 72.9%, 23.5% and 3.5% respectively. There was no significant statistical difference in risk for lung cancer between the groups of GA, AA, GA＋AA and the group of GG. After a balance in age, sex, and smoking status of all subjects, compared with group of GG genotype, the OR of the group of GA genotype, AA genotype and GA＋AA genotype are 0.83 （95% CI：0.49-1.41）, 0.18 （95% CI：0.02-1.59） and 0.76 （95% CI：0.45-1.27） respectively. In patients with small cell lung cancer, GA genotypic individuals had better platinum-based chernothempy responsive tendency compared with GG genotype. The non-small cell lung cancer patients with GG genotype also had better chemotherapy responsive tendency compared with GA＋AA genotype. Conclusion The data suggests that the genetic pelymorphism of elF3a 2554G〉A may be associated with platinum-based chemotherapy sensitivity in Chinese patients wi

关 键 词：真核细胞翻译起始因子3a 肺癌 单核苷酸多态性 化疗敏感性 

分 类 号：R734.2[医药卫生—肿瘤] R979.1[医药卫生—临床医学]