Oncotarget

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Genetic polymorphisms of mTOR and cancer risk: a systematic review and updated meta-analysis

Jin Zining, Xu Lu, He Caiyun and Yuan Yuan _

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Oncotarget. 2016; 7:57464-57480. https://doi.org/10.18632/oncotarget.10805

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Abstract

Jin Zining1,*, Xu Lu1,*, He Caiyun2 and Yuan Yuan1

1 Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention of Liaoning Provincial Education Department, The First Affiliated Hospital of China Medical University, Shenyang, China

2 Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

* These authors have contributed equally to this work, and thus, they were considered as co-first authors

Correspondence to:

Yuan Yuan, email:

Keywords: mTOR; polymorphism; cancer risk; systematic review; meta-analysis

Received: March 03, 2016 Accepted: June 29, 2016 Published: July 24, 2016

Abstract

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.


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PII: 10805