Dataset Information

Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

ABSTRACT: Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and acute myeloid leukemia risk (AML) have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C) polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls) and 9 studies (1335 patients and 4295 controls) for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98-1.04; 95% CI, 0.86-0.92 to 1.09-1.25). Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis.

SUBMITTER: Qin YT

PROVIDER: S-EPMC3930602 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

Qin Yu-Tao YT Zhang Yong Y Wu Fang F Su Yan Y Lu Ge-Ning GN Wang Ren-Sheng RS

PloS one 20140220 2

Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and acute myeloid leukemia risk (AML) have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C) polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs) ...[more]

PMID: 24586405

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Project description:BACKGROUND:Since the 1990s, there have been a lot of research on single-nucleotide polymorphism (SNP) and different diseases, including many studies on 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and essential hypertension (EH). Nevertheless, their conclusions were controversial. So far, six previous meta-analyses discussed the internal relationship between the MTHFR polymorphism and EH, respectively. However, they did not evaluate the credibility of the positive associations. To build on previous meta-analyses, we updated the literature by including previously included papers as well as nine new articles, improved the inclusion criteria by also considering the quality of the papers, and applied new statistical techniques to assess the observed associations. OBJECTIVES:This study aims to explore the degree of risk correlation between two MTHFR polymorphisms and EH. METHODS:PubMed, EMBASE, the Cochrane Library, CNKI, and Wan Fang electronic databases were searched to identify relevant studies. We evaluated the relation between the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and EH by calculating the odds ratios (OR) as well as 95% confidence intervals (CI). Here we used subgroup analysis, sensitivity analysis, cumulative meta-analysis, assessment of publication bias, meta-regression meta, False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and Venice criterion. RESULTS:Overall, harboring the variant of MTHFR C677T was associated with an increased risk of EH in the overall populations, East Asians, Southeast Asians, South Asians, Caucasians/Europeans, and Africans. After the sensitivity analysis, positive results were found only in the overall population (TT vs. CC: OR = 1.14, 95% CI: 1.00-1.30, P h = 0.032, I 2 = 39.8%; TT + TC vs. CC: OR = 1.15, 95% CI: 1.01-1.29, P h = 0.040, I 2 = 38.1%; T vs. C: OR = 1.14, 95% CI: 1.04-1.25, P h = 0.005, I 2 = 50.2%) and Asian population (TC vs. CC: OR = 1.14, 95% CI: 1.01-1.28, P h = 0.265, I 2 = 16.8%; TT + TC vs. CC: OR = 1.17, 95% CI: 1.04-1.30, P h = 0.105, I 2 = 32.9%; T vs. C: OR = 1.10, 95% CI: 1.02-1.19, P h = 0.018, I 2 = 48.6%). However, after further statistical assessment by FPRP, BFDP, and Venice criteria, the positive associations reported here could be deemed to be false-positives and present only weak evidence for a causal relationship. In addition, when we performed pooled analysis and sensitivity analysis on MTHFR A1298C; all the results were negative. CONCLUSION:The positive relationships between MTHFR C677T and A1298C polymorphisms with the susceptibility to present with hypertension were not robust enough to withstand statistical interrogation by FPRP, BFDP, and Venice criteria. Therefore, these SNPs are probably not important in EH etiology.

Project description:Previous studies have shown that the single nucleotide polymorphisms (SNPs) in Methylenetetrahydrofolate reductase (MTHFR) and Glutathione S-transferases (GSTs, including GSTM1, GSTT1) genes play an important role in determining the response of an individual to environmental pathogenesis and significantly relate to incidences of various human tumors, including brain tumors. However, these genes' polymorphisms on meningioma risk remains poorly understood. The relevant inferences from previous studies are hindered by their limited statistical power and conflicting results. The aim of this meta-analysis is to provide a relatively comprehensive account of the association between these polymorphisms and human meningioma risk. A literature search for eligible studies published before January 1, 2014 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases. Pooled odds ratios (OR) with their corresponding 95% confidence intervals (95% CI) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. Heterogeneity and publication bias were evaluated. All statistical analyses were conducted by using the software of STATA 12.0 (STATA Corporation, College Station, TX, USA). For MTHFR C677T (dbSNP: rs1801133) (C T) polymorphism, 9 individual case-control studies from six publications with 1,615 cases and 1,909 controls were obtained. For GSTM1 null polymorphism, there were 4 studies with 417 cases and 1,735 controls. For GSTT1 null polymorphism, there were 4 studies with 405 cases and 1,622 controls. The combined results for the MTHFR C677T show that carriers of the CT genotype may be associated with a higher meningioma risk (OR = 1.20, 95% CI 1.05-1.38, P = 0.009). Stratified analyses show that Caucasians have significantly higher risk if they carry the CT genotype of MTHFR (OR = 1.31, 95% CI 1.05-1.63, P = 0.02). Risk of Caucasians carrying TT + CT genotype is also significantly higher (OR = 1.27, 95% CI 1.02-1.58, P = 0.03). Risk of Caucasians carrying TT genotype is not significantly different compared to control population (OR = 0.96, 95% CI 0.69-1.34, P = 0.82). All of the enrolled studies about GSTM1/GSTT1 are on Caucasians. The pooled ORGSTM1 and ORGSTT1 were not significant in Caucasian population. These results indicate SNPs of MTHFR C677T are related to meningioma risk with ethnic differences. Caucasians carrying CT genotype of MTHFR C677T have significantly higher meningioma susceptibility. SNPs of GSTM1/GSTT1 are not related to meningioma risk.

Dataset Information

Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

Publications

Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

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