mTOR启动子区基因多态性与肾癌发病风险的关系

Polymorphism in the mTOR promoter is associated with risk of renal cell carcinoma

目的： mTOR信号通路在肾癌的形成过程中起着重要作用。本研究旨在探索mTOR信号通路相关基因多态性与肾癌易感性的关系。方法采用病例‐对照研究，对710例肾癌患者和760例健康人群，应用 TaqMan探针分型法对 AKT1、AKT2、PTEN和mTOR基因功能区8个基因多态性进行分型。控制混杂因素，应用非条件逻辑回归，评价基因多态性与肾癌的关系。结果在8个基因多态性位点中，我们通过校正后的多因素分析发现位于mTOR启动子区的（rs2295080）与肾癌的风险成负相关（P＝0．005，OR＝0．74，95％ CI＝0．59～0．91，TG／GG vs ．TT）。另一位于PTEN基因3＇端非翻译区的位点，其多态性与肾癌的风险成正相关（P＝0．014，OR＝1．45，95％ CI＝1．08～1．96，CC vs ．TT），然而通过校正后的多因素分析，我们发现上述关系在统计学上并无明显统计学意义。此外，rs2295080 G等位基因肾脏组织中，mTOR表达水平明显降低。没有发现其他几个多态性位点与肾癌风险存在明显的相关性。结论位于mTOR启动子区的rs2295080多态性与肾癌的易感性有关。

ABSTRACT：Objective To explore the association between the polymorphism of mTOR pathway‐related genes and risk of renal cell carcinoma （RCC ） .Methods Eight potentially functional polymorphisms in AKT1 , AKT2 , PTEN and mTOR genes were genotyped using the TaqMan method in a case‐control study of 710 RCC patients and 760 cancer‐free subjects .Un‐conditional logistic regression ,adjusted for potential confounding factors ,was used to assess the risk associations .Results Of the 8 polymorphisms ,after being adjusted for multiple comparisons ,a significant association was found between one variant （rs2295080） in the promoter of mTOR and reduced RCC risk （ P=0 .005 , OR=0 .74 ,95% CI=0 .59 -0 .91 ,TG/GG vs . TT） .Another variant （rs701848） in the 3＇UTR region of PTEN was associated with increased RCC risk （ P= 0 .014 , OR=1.45 ,95% CI=1 .08-1 .96 ,CC vs .TT）;however ,the association was not significant after being adjusted for multiple com‐parisons .Furthermore ,lower mTOR mRNA levels were observed in the presence of the rs2295080G allele in normal renal tis‐sues .No other significant association between the selected polymorphisms and RCC risk was observed .Conclusion Our re‐sults suggest that the mTOR promoter rs2295080 variant affects RCC susceptibility ,which needs further validation .