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Association of mTOR polymorphisms with cancer risk and clinical outcomes: a meta-analysis.

Shao J, Li Y, Zhao P, Yue X, Jiang J, Liang X, He X - PLoS ONE (2014)

Bottom Line: However, inconsistent results have been reported.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.

View Article: PubMed Central - PubMed

Affiliation: Department of CT/MRI, Wuhan Children's Hospital, Hubei, China.

ABSTRACT
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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Related in: MedlinePlus

Flow of study identification, inclusion, exclusion.
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pone-0097085-g001: Flow of study identification, inclusion, exclusion.

Mentions: Through the primary literature research in Pubmed, 61 studies were identified for cancer risk and/or clinical outcome assessment for mTOR polymorphisms. However, after manually screening the titles and abstracts, 43 studies were excluded. 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. 1. For cancer risk assessment, all 7 studies were conducted in Chinese population, including 5798 cancer patients and 6244 healthy controls. The types of cancers included renal cell cancer, acute lymphoblastic leukemia, prostate cancer, gastric cancer, and esophageal squamous cell carcinoma. Of the 7 studies, 3 studies used population-based and frequency-matched controls to the cases by the age and region [13], [17]–[18]. All studies used TaqMan SNP Genotyping Assay and randomly repeated assays for genotyping quality control. The genotypes in the controls in all studies were in Hardy-Weinberg equilibrium. For estimating the influence of mTOR polymorphisms (rs2295080 and rs11121704) on clinical outcomes in cancer patients, 4 eligible studies included 1594 cancer patients, were identified: 2 were conducted in USA [19], [20] and two were in China [14], [35]. Two studies in USA evaluating evaluated more than one clinical outcome parameter, and these parameters were separately analyzed as separate observations. All studies extracted DNA from peripheral blood lymphocytes for genotyping except for one study, where tumor tissue was used. The essential information for all studies was shown in Table 1 and 2.


Association of mTOR polymorphisms with cancer risk and clinical outcomes: a meta-analysis.

Shao J, Li Y, Zhao P, Yue X, Jiang J, Liang X, He X - PLoS ONE (2014)

Flow of study identification, inclusion, exclusion.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016248&req=5

pone-0097085-g001: Flow of study identification, inclusion, exclusion.
Mentions: Through the primary literature research in Pubmed, 61 studies were identified for cancer risk and/or clinical outcome assessment for mTOR polymorphisms. However, after manually screening the titles and abstracts, 43 studies were excluded. 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. 1. For cancer risk assessment, all 7 studies were conducted in Chinese population, including 5798 cancer patients and 6244 healthy controls. The types of cancers included renal cell cancer, acute lymphoblastic leukemia, prostate cancer, gastric cancer, and esophageal squamous cell carcinoma. Of the 7 studies, 3 studies used population-based and frequency-matched controls to the cases by the age and region [13], [17]–[18]. All studies used TaqMan SNP Genotyping Assay and randomly repeated assays for genotyping quality control. The genotypes in the controls in all studies were in Hardy-Weinberg equilibrium. For estimating the influence of mTOR polymorphisms (rs2295080 and rs11121704) on clinical outcomes in cancer patients, 4 eligible studies included 1594 cancer patients, were identified: 2 were conducted in USA [19], [20] and two were in China [14], [35]. Two studies in USA evaluating evaluated more than one clinical outcome parameter, and these parameters were separately analyzed as separate observations. All studies extracted DNA from peripheral blood lymphocytes for genotyping except for one study, where tumor tissue was used. The essential information for all studies was shown in Table 1 and 2.

Bottom Line: However, inconsistent results have been reported.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.

View Article: PubMed Central - PubMed

Affiliation: Department of CT/MRI, Wuhan Children's Hospital, Hubei, China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus