PI3K-AKT-mTOR信号通路基因多态性与胃癌遗传易感相关性  

Association of SNP in the PI3K-PTEN-AKT-mTOR pathway with genetic susceptibility of gastric cancer

作　　者：林贤东[1,2,3] 胡丹[2] 陈刚 师怡[2] 张和军[2] 金善丰[2] 李鑫静[2] 郑雄伟[1,2,3] 

机构地区：[1]福建医科大学教学医院,福州350014 [2]福建省肿瘤医院病理科,福州350014 [3]福建省肿瘤转化重点实验室,福州350014

出　　处：《临床与实验病理学杂志》2016年第4期361-365,369,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：国家临床重点专科建设项目;福建省自然科学基金(2014J0101);福建省卫计委创新课题(2015-CX-7);福建省卫计委中青年骨干人才培养项目(2013-ZQN-JC-8;2015-ZQN-JC-7)

摘　　要：目的 探讨中国福建地区汉族人群PI3K/AKT/mT0R信号通路基因单核苷酸多态性（single nucleotide polymorphism,SNP）与胃癌遗传易感性的关系。方法 选取组织学确诊的胃癌323例及年龄和性别等频数匹配的对照健康体检人493例,采用PCR-连接酶检测反应（ligase detection reaction,PCR-LDR）法进行PI3Krs7651265A〉G、mTORrs7212142G〉A及AKT rs1130214G〉T多态性检测,应用非条件Logistic回归分析评估不同基因型与胃癌发病风险及病理特征的关系。采用似然比检验分析PI3K和mTOR基因多态性之间的交互作用。结果 PI3K基因rs7651265携带G等位基因（GG＋GA）患者发生胃癌的风险是携带AA基因型的4.93倍（P〈0.05）。而该位点携带AA基因型的患者发生肿瘤浸润的风险是携带GG＋AG基因型患者的3.5倍（P〈0.05）。mTORrs7212142携带GG基因型的患者发生淋巴结转移的风险是携带AA＋AG基因型的1.67倍（P〈0.05）。采用似然比检验分析表明,PI3Krs7651265A〉G和mTORrs7212142G〉A基因多态性间存在明显交互作用。与携带野生型纯合子PI3KAA和mTORGG基因型的个体相比,位点发生变异的PI3K（AG＋GG）mTOR（GG）、PI3K（AG＋GG）mTOR（AG＋AA）增加个体患胃癌的风险,OR值分别为5.71（95%CI：3.50-9.34,P〈0.05）和6.41（95%CI：4.13-9.90,P〈0.05）。结论 PI3K-AKT-mTOR信号通路基因多态性与胃癌的发生及侵袭转移密切相关,有可能成为胃癌预后的新分子指标。Purpose To explore the correlations between single-nucleotide polymorphisms （SNP） in the PI3K/AKT/mTOR pathway and the genetic susceptibility of gastric carcinoma （GC） in Fujian province, China. Methods A case-control study was conducted in a population in Fujian province. Polymorphisms of PI3K rs7651265 A 〉 G, mTOR rs7212142 G 〉 A and AKT rs1130214 G 〉 T in 323 gastric carcinoma patients and 493 cancer-free controls, frequency-matched by age and sex, were determined by PCR-ligase detection reaction （PCR-LDR）. Adjusted odds ratios （ORs） and 95% confidence evaluate intervals （95% CI） were measured by multivariate logistic regression analysis to investigate the correlations of the polymorphisms to the susceptibility to gastric cancer. Tests for an interaction between the PI3K rs7651265 A 〉 G and roTOR rs7212142 G 〉 A were performed using the likelihood ratio test. Results As compared with AA genotype, patients with GG ＋ AG of PI3K rs7651265 had a significantly higher risk of the cancer with OR of 4. 93 （ P 〈 0. 05 ）. And comparing to GG ＋ AG genotype, patients with AA of PI3K rs7651265 had a significantly higher risk in tumor invasion with OR of 3.5 （P 〈 0. 05 ）. When compared with AA ＋ AG genotype, patients with GG of roTOR rs7212142 had a significantly higher risk in lymph node metastasis with OR of 1.67 （ P 〈 0. 05 ）. There was significant interaction between the polymorphisms of PI3K rs7651265 A 〉 G and mTOR rs7212142 G 〉 A observed by the likelihood ratio test. When compared with the wild homozygous PI3K AA and mTOR GG. PI3K （AG ＋ GG） ＊ roTOR （GG） and PI3K （AG ＋ GG） ＊ roTOR （ AG ＋ AA） genotype carriers, there was a significantly increase of risk in gastric carcinogenesis of 5.71 （P 〈 0. 05 ） and 6.41 （ P 〈 0. 05 ）, respectively. Conclusion Polymorphisms of PI3K-AKT-mTOR pathway is significantly related with occurrence and development of GC and it may be a new biomarker of GC for prognosis.

关 键 词：胃肿瘤 PI3K-AKT-mTOR信号通路 单核苷酸多态性 疾病遗传易感性 

分 类 号：R735.2[医药卫生—肿瘤]