PI3K-AKT-mTOR信号通路基因多态性与胃癌遗传易感相关性
发布时间：2018-10-16 22:16
【摘要】：目的探讨中国福建地区汉族人群PI3K/AKT/mTOR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PI3K rs7651265 AG、mTOR rs7212142 GA及AKT rs1130214 GT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(P0.05)。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(P0.05)。mTOR rs7212142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(P0.05)。采用似然比检验分析表明,PI3K rs7651265 AG和mTOR rs7212142 GA基因多态性间存在明显交互作用。与携带野生型纯合子PI3K AA和mTOR GG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,P0.05)和6.41(95%CI:4.13~9.90,P0.05)。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。
[Abstract]:Objective to investigate the relationship between single nucleotide polymorphisms (single nucleotide polymorphism,SNP) of PI3K/AKT/mTOR signaling pathway gene and genetic susceptibility of gastric cancer in Fujian Han population. Methods the polymorphism of PI3K rs7651265 AG,mTOR rs7212142 GA and AKT rs1130214 GT were detected by PCR- ligase assay (ligase detection reaction,PCR-LDR) in 323 cases of histologically diagnosed gastric cancer and 493 healthy controls with matched age and sex. Non-conditional Logistic regression analysis was used to evaluate the relationship between different genotypes and the risk and pathological features of gastric cancer. The interaction between PI3K and mTOR gene polymorphism was analyzed by likelihood ratio test. Results the risk of gastric cancer in patients with PI3K rs7651265 carrying G allele (GG GA) was 4.93 times higher than that with AA genotype (P0.05). The risk of tumor invasion in patients with AA genotype was 3.5 times higher than that in patients with GG AG genotype (P0.05). The risk of lymph node metastasis in patients with GG genotype was 1.67 times higher than that in patients with GG genotype (P0.05). The analysis of likelihood ratio test showed that there was obvious interaction between PI3K rs7651265 AG and mTOR rs7212142 GA gene polymorphism. Compared with the individuals with wild type homozygous PI3K AA and mTOR GG genotypes, PI3K (AG GG) * mTOR (GG), PI3K (AG GG) * mTOR (AG AA) with variant loci increased the risk of gastric cancer, with OR values of 5.71 (95 CI: 3.50) and 6.41 (95CI: 4.130.9.90), respectively. Conclusion Polymorphism of PI3K-AKT-mTOR signaling pathway is closely related to the occurrence, invasion and metastasis of gastric cancer, which may be a new molecular marker for the prognosis of gastric cancer.
【作者单位】： 福建医科大学教学医院;福建省肿瘤医院病理科;福建省肿瘤转化重点实验室;
【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)
【分类号】：R735.2
，
本文编号：2275792
[Abstract]:Objective to investigate the relationship between single nucleotide polymorphisms (single nucleotide polymorphism,SNP) of PI3K/AKT/mTOR signaling pathway gene and genetic susceptibility of gastric cancer in Fujian Han population. Methods the polymorphism of PI3K rs7651265 AG,mTOR rs7212142 GA and AKT rs1130214 GT were detected by PCR- ligase assay (ligase detection reaction,PCR-LDR) in 323 cases of histologically diagnosed gastric cancer and 493 healthy controls with matched age and sex. Non-conditional Logistic regression analysis was used to evaluate the relationship between different genotypes and the risk and pathological features of gastric cancer. The interaction between PI3K and mTOR gene polymorphism was analyzed by likelihood ratio test. Results the risk of gastric cancer in patients with PI3K rs7651265 carrying G allele (GG GA) was 4.93 times higher than that with AA genotype (P0.05). The risk of tumor invasion in patients with AA genotype was 3.5 times higher than that in patients with GG AG genotype (P0.05). The risk of lymph node metastasis in patients with GG genotype was 1.67 times higher than that in patients with GG genotype (P0.05). The analysis of likelihood ratio test showed that there was obvious interaction between PI3K rs7651265 AG and mTOR rs7212142 GA gene polymorphism. Compared with the individuals with wild type homozygous PI3K AA and mTOR GG genotypes, PI3K (AG GG) * mTOR (GG), PI3K (AG GG) * mTOR (AG AA) with variant loci increased the risk of gastric cancer, with OR values of 5.71 (95 CI: 3.50) and 6.41 (95CI: 4.130.9.90), respectively. Conclusion Polymorphism of PI3K-AKT-mTOR signaling pathway is closely related to the occurrence, invasion and metastasis of gastric cancer, which may be a new molecular marker for the prognosis of gastric cancer.
【作者单位】： 福建医科大学教学医院;福建省肿瘤医院病理科;福建省肿瘤转化重点实验室;
【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)
【分类号】：R735.2
，
本文编号：2275792
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