Genetic polymorphisms of mTOR and cancer risk: a systematic review and updated meta-analysis.
Genetic polymorphisms of mTOR and cancer risk: a systematic review and updated meta-analysis.
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DOI：
10.18632/oncotarget.10805
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发表时间：
2016-08-30
期刊：
影响因子：
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通讯作者：
Yuan Y
中科院分区：
文献类型：
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作者：
Zining J;Lu X;Caiyun H;Yuan Y
mTOR调节几个对肿瘤发生至关重要的细胞过程。然而，以往关于mTOR多态性与不同类型癌症易感性之间关系的研究有些矛盾。因此，我们对mTOR单核苷酸多态性（snp）与癌症风险之间关系的现有证据进行了系统回顾和更新的荟萃分析。截至2015年11月，共鉴定到23篇原始文献，涉及20个mTOR snp，其中7个snp （rs2536、rs2295080、rs1883965、rs1034528、rs17036508、rs3806317和rs1064261）被纳入最终meta分析。我们估计了mTOR多态性与癌症风险的总比值比（ORs）和相应的95%置信区间（CIs），并使用无模型方法研究每种多态性的生物学效应。我们的荟萃分析发现，在完全过显性模型中，rs1883965、rs1034528和rs17036508与癌症风险增加相关（rs1883965 GA与GG/AA：固定效应OR=1.15, 95% CI 1.02-1.29； rs1034528 GC与GG/CC：固定效应OR=1.30, 95% CI 1.13-1.48； rs17036508 TC与CC/TT：固定效应OR=1.23, 95% CI 1.06-1.43）。根据癌症类型进行分层分析，我们发现rs2295080 G等位基因与隐性模型中较高的急性白血病风险相关（GG vs GT/TT：固定效应OR=2.08, 95% CI 1.34-3.22），与显性模型中较低的泌尿生殖系统癌风险相关（TG/GG vs TT：固定效应OR=0.77, 95% CI 0.68-0.86）。有趣的是，进一步的表达分析显示，基于HapMap数据，rs1883965、rs1034528和rs17036508纯合子变异基因型携带者的mTOR转录水平较低。
mTOR regulates several cellular processes that are critical for tumorigenesis. However, previous studies on the association of mTOR polymorphisms with predisposition to different cancer types are somewhat contradictory. Therefore, we performed a systematic review and updated meta-analysis of the available evidence regarding the relationship between mTOR single nucleotide polymorphisms (SNPs) and cancer risk. Up to November 2015, 23 original publications were identified covering 20 mTOR SNPs, of which seven SNPs (rs2536, rs2295080, rs1883965, rs1034528, rs17036508, rs3806317 and rs1064261) were included in the final meta-analysis. We estimated the summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for mTOR polymorphisms and cancer risk, and used the model-free approach to investigate the biological effect of each polymorphism. Our meta-analysis found that rs1883965, rs1034528, and rs17036508 were correlated with increased cancer risk in the complete over-dominant model (rs1883965 GA versus GG/AA: fixed-effects OR=1.15, 95% CI 1.02-1.29; rs1034528 GC versus GG/CC: fixed-effects OR=1.30, 95% CI 1.13-1.48; rs17036508 TC versus CC/TT: fixed-effects OR=1.23, 95% CI 1.06-1.43). Stratifying analyses by cancer type, we found that the rs2295080 G allele was associated with a significantly higher risk of acute leukemia in the recessive model (GG versus GT/TT: fixed-effects OR=2.08, 95% CI 1.34-3.22) and a lower risk of genitourinary cancers in the dominant model (TG/GG versus TT: fixed-effects OR=0.77, 95% CI 0.68-0.86). Interestingly, further expression analysis showed that homozygous variant genotype carriers of rs1883965, rs1034528 and rs17036508 had lower mTOR transcript levels, based on HapMap data.