Association of genetic variations in<i>mTOR</i>with risk of childhood acute lymphoblastic leukemia in a Chinese population

Huang, Lizhen; Huang, Jie; Wu, Peng; Li, Qian; Rong, Liucheng; Xue, Yue; Lü, Qing; Li, Jie; Tong, Na; Wang, Meilin; Zhang, Zhengdong; Fang, Yongjun

doi:10.3109/10428194.2011.628062

Cited by 24 publications

(34 citation statements)

References 29 publications

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“…This may be the first report that an mTOR intron rs1883965G>A SNP is associated with gastric cancer risk. In another published study, however, the mTOR rs2536 TC heterozygous genotype was found to be associated with a significantly decreased risk in a study of Chinese childhood acute lymphoblastic leukemia with 417 patients and 554 controls , but this risk was not found in the present study that had a doubled study sample size. It is possible that this risk may be cancer type‐specific.…”

Section: Discussioncontrasting

confidence: 88%

Genetic variations of mTORC1 genes and risk of gastric cancer in an eastern chinese population

Wang

Qiu

et al. 2013

Molecular Carcinogenesis

120

104

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Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false-positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00-1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67-5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03-1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04-1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever-smokers, non-gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two-factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations.

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Section: Discussioncontrasting

confidence: 88%

Genetic variations of mTORC1 genes and risk of gastric cancer in an eastern chinese population

Wang

Qiu

et al. 2013

Molecular Carcinogenesis

120

104

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“…All studies that focused on Chinese populations indicated an association between rs2295080 GT/GG and cancer risk, suggesting an possibly ethnic-specific association. Nevertheless, the associations between mTOR rs2536 C variant or genotypes and cancer risk in Chinese populations were various in the literatures; for example, the mTOR rs2536 CT heterozygous genotype was found to be associated with decreased risk of Chinese childhood acute lymphoblastic leukemia [28]; however, this association was not observed in other tumor types, such as gastric cancer [29], prostate cancer [24], and esophageal squamous cell carcinoma [30]. On the contrary, in the present study, we found that the mTOR rs2536 CT/CC genotypes were associated with an increased PCa risk under a dominant genetic model, different from the findings of another previously published PCa study (666 cases and 708 controls), in which a null association was reported [24].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the mTOR Gene and Risk of Sporadic Prostate Cancer in an Eastern Chinese Population

Zhu

et al. 2013

PLoS ONE

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BackgroundThe mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk.Methodology/Principal FindingsIn a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis.Conclusions/SignificancesIn the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13–1.78), P = 0.003 and 1.29 (1.07–1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64–0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04–1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies.

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“…The remaining 18 articles were reviewed and, 8 of them were removed due to lack of sufficient data or examing other mTOR polymorphisms but not rs2295080, rs2536 (T>C) and rs11121704 [26]–[33]. Finally, 10 studies were met the inclusion criteria [12]–[20], [35], and 6 studies evaluated the influence on cancer risks [12]–[13], [15]–[18] and 3 assessed the clinical outcomes [19], [20], [35], such as death, metastasis, resistance to chemotherapy, and toxicity, and one examined both [14]. The flow of study identification, inclusion, exclusion was shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Association of mTOR Polymorphisms with Cancer Risk and Clinical Outcomes: A Meta-Analysis

Shao

Zhao

et al. 2014

PLoS ONE

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Genetic polymorphisms in mTOR gene may be associated with cancer risk and clinical outcomes of cancer patients by affecting mTOR gene expression or its activation. However, inconsistent results have been reported. The aim of this study is to systematically evaluate the association between mTOR polymorphisms (rs2295080, rs2536 and rs11121704) and cancer risk as well as clinical outcome by a meta-analysis. We identified 10 eligible studies and extracted data by two investigators. Based on dominant and recessive models, odds ratio (ORs) and 95% confidence intervals (CIs) were calculated by using Stata, version 11 to evaluate the association strength. Our meta-analysis results showed that the wild genotype TT of rs2295080 polymorphism was associated with increased cancer risk under dominant model (OR = 1.24, 95%CI: 1.12–1.36, p<0.0005) in Chinese but not with clinical outcome parameters, while the TT genotype of rs11121704 was associated with poor clinical outcome parameters (OR = 1.53, 95%CI: 1.01–2.32, p = 0.044), such as death, metastasis and resistance to chemotherapy. However, rs2536 may not influence cancer susceptibility. In conclusion, this meta-analysis indicated the common polymorphisms in mTOR gene might be genetic risk factors for the carcinogenesis and clinical outcomes of cancer patients. However, further investigation on large population and different ethnicities are warranted.

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Association of genetic variations inmTORwith risk of childhood acute lymphoblastic leukemia in a Chinese population

Cited by 24 publications

References 29 publications

Genetic variations of mTORC1 genes and risk of gastric cancer in an eastern chinese population

Genetic variations of mTORC1 genes and risk of gastric cancer in an eastern chinese population

Polymorphisms in the mTOR Gene and Risk of Sporadic Prostate Cancer in an Eastern Chinese Population

Association of mTOR Polymorphisms with Cancer Risk and Clinical Outcomes: A Meta-Analysis

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