贵州医科大学学报

2017, v.42;No.205(10) 1149-1154

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mTOR启动子区域的基因多态性与汉族人群甲状腺癌发病风险的关联性
Association of Genetic Polymorphisms in the mTOR Promoter Region with Thyroid Cancer Morbidity in Han Population

文静;时立新;
WEN Jing;SHI Lixin;Ultrasound Center,the Affiliated Hospital of Guizhou Medical University;Endocrine Department,the Affiliated Hospital of Guizhou Medical University;

摘要(Abstract):

目的:探讨mTOR基因启动子区域单核苷酸多态性(SNP)rs2295080与甲状腺癌(TC)发病风险的关联性。方法:选取汉族甲状腺乳头状癌(PTC)患者560名(病例组)及同期汉族正常对照人群500名(观察组),统计两组人群中rs2295080 TT、TG和GG基因型的分布频率,采用非条件性Logistic回归以及趋势性检验评估mTOR基因多态性rs2295080不同基因型频率和TC发病风险的关联性以及rs2295080多态性与TC人群中年龄、性别以及TC临床变量的关联性,通过荧光素酶报告基因方法检测rs2295080多态性对Nthy-ori3-1和TPC-1细胞系转录活性的影响。结果:病例组rs2295080 TT、TG和GG基因型的分布频率分别为65.4%、30.4%和4.3%,对照组为59.0%、35.2%和5.8%;logistic抑制性模型检验显示,与T等位基因比较,G等位基因能够显著降低TC发病风险(P=0.004,矫正OR=0.72,95%CI=0.63~0.87);趋势性检验显示,TC发病风险与G等位基因存在剂量依赖性;对于TC,m TOR rs2295080在男性人群中具有保护性效应(P<0.001,矫正OR=0.55,95%CI=0.42~0.76);在原发肿瘤、淋巴结转移及远端转移中,rs2295080多态性与TC临床变量多存在保护性效应;荧光素酶报告显示,在Nthy-ori3-1和TPC-1细胞系中,T等位基因的转录活性均高于G等位基因。结论:m TOR基因启动子多态性rs2295080与汉族人群TC的发病风险有关联,其G等位基因可能是TC发病中一个保护性基因。
Objective: To investigate the association between single nucleotide polymorphism in m TOR promoter region and thyroid cancer morbidity. Methods: A total of 560 patients with thyroid papillary carcinoma( PTC) in Han nationality and 500 normal controls in the same period( observation group) were selected. TT,TG and GG genotype frequencies of rs2295080 were measured in two groups. Non conditional Logistic regression and trend test were used to assess the association between m TOR genotype polymorphism,rs2295080 genotype frequency and risk of TC,as well as the association between rs2295080 polymorphism and age,sex,and TC clinical variables in TC population. The effect of rs2295080 polymorphism on transcriptional activity of Nthy-ori3-1 and TPC-1 cell lines was examined by luciferase reporter gene assay. Results: The frequencies of TT,TG and GG genotypes of rs2295080 were 65. 4%,30. 4% and 4. 3% in the case group,59%,35. 2% and 5. 8% in the control group respectively; Logistic suppression model test showed that G allele could significantly reduce the risk of TC in comparison with T allele( P = 0. 004,corrected OR = 0. 72,95% CI = 0. 63 ~ 0. 87).The trend test showed that the risk of TC was dose-dependent with G alleles; For TC,m TOR rs2295080 has a protective effect in male populations( P < 0. 001,corrected OR = 0. 55,95% CI = 0. 42~ 0. 76). In the primary tumor,lymph node metastasis and distant metastasis,rs2295080 polymorphism have protective effect; Luciferase reports showed that in Nthy-ori3-1 and TPC-1 cell lines the transcriptional activity of the T allele was higher than that of the G allele. Conclusions: The polymorphism of m TOR gene promoter is associated with the risk of TC in Han population,and its G allele may be a protective gene in the pathogenesis of TC.

关键词(KeyWords): 单核苷酸多态性;甲状腺癌;mTOR;启动子区;汉族
single nucleotide polymorphism;thyroid cancer;mTOR;promoter region

Abstract:

Keywords:

基金项目(Foundation): 贵州省科技计划项目[黔科合基础(2016)1122]

作者(Author): 文静;时立新;
WEN Jing;SHI Lixin;Ultrasound Center,the Affiliated Hospital of Guizhou Medical University;Endocrine Department,the Affiliated Hospital of Guizhou Medical University;

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DOI: 10.19367/j.cnki.1000-2707.2017.10.008

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