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The TNF-alpha-238 polymorphism and cancer risk: a meta-analysis.

ABSTRACT: BACKGROUND AND OBJECTIVES: Tumor necrosis factor-? (TNF-?) plays a very important role in the development and progress of cancer. Some TNF-? polymorphisms have been confirmed to increase cancer risks; however, the association between TNF-?-238 polymorphism and cancers remains controversial and ambiguous. The aim of this study is to explore a more precise estimation of its relationship with cancer using meta-analysis. METHODS: Electronic searches of several databases were conducted for all publications on the association between this variant and cancer through March 2011. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association in the random-effect model. RESULTS: Thirty four studies with 34,679 cancer patients and 41,186 healthy controls were included. This meta-analysis showed no significant association between TNF-?-238 polymorphism and cancers (AA+GA vs GG: OR?=?1.09, 95%CI?=?0.88-1.34). In Caucasian and Asian subgroups, OR values (95% CI) were 1.14 (0.91-1.43) and 0.97 (0.58-1.61), respectively. In the subgroups of cancer type, no significant association was detected. The sensitivity analysis further strengthened the validity of these negative associations. No publication bias was observed in this study. CONCLUSIONS: No significant association was found between the TNF-?-238 polymorphism and the risk for cancer.

SUBMITTER: Zhou P

PROVIDER: S-EPMC3139602 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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The TNF-alpha-238 polymorphism and cancer risk: a meta-analysis.

Zhou Ping P Lv Guo-Qiang GQ Wang Jian-Zhong JZ Li Cheng-Wan CW Du Liang-Feng LF Zhang Chun C Li Jian-Ping JP

PloS one 20110719 7

<h4>Background and objectives</h4>Tumor necrosis factor-α (TNF-α) plays a very important role in the development and progress of cancer. Some TNF-α polymorphisms have been confirmed to increase cancer risks; however, the association between TNF-α-238 polymorphism and cancers remains controversial and ambiguous. The aim of this study is to explore a more precise estimation of its relationship with cancer using meta-analysis.<h4>Methods</h4>Electronic searches of several databases were conducted f ...[more]

PMID: 21818296

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Project description:Individual studies have assessed the association between TNF-α-308G>A and TNF-α-238 G>A polymorphisms and severity of dengue infection. However, the results are inconclusive and most studies had small sample sizes. The objective of this study was to summarize the evidence of association between TNF-α-308 G>A and TNF-α-238 G>A and severity of dengue infection. This study follows the preferred reporting items for systematic reviews and meta- analyses of genetic association studies, recommended by PLOS One. We calculated pooled odds ratio and its 95% confidence interval (CI) to estimate the association between TNF-α-308 G>A or TNF-α-238 G>A and the risk of severe dengue infections. To determine the information size required for this meta-analysis study, a trial sequential analysis (TSA) was done. Eight studies (640 cases and 1275 controls), which assessed the association of TNF-α-308 G>A or TNF-α-238 G>A and the risk of DHF were included. Overall, we found no significant association between TNF-α-308 G>A and the DHF risk in the allelic model (OR, 0.91; 95% CI, 0.51-1.63), the recessive model (OR,1.32;95%CI,0.73-2.37), the dominant model (OR,0.93;95%CI:0.59-1.47) or the additive model (OR,1.43,95;95%CI:0.79-2.59). There was also no significant association between TNF-α-238 G>A and DHF risk under the allele contrast model (OR:1.51;95%CI:0.88-2.58), the recessive model (OR,1.48,95% CI:0.33-6.58), the dominant model (OR,1.48;95%CI:0.56-3.92), or the additive model (OR:1.5;95%CI:0.34-6.69). On subgroup analysis, neither the Asian population nor the non-Asian population showed significant association between TNF-α-308 G>A/TNF-α-238 G>A and the DHF risk under any genetic models. Leave-one-out meta-analysis showed stability of the results. TSA plots suggested that the sample size in this meta-analysis study was below the required information size. The findings suggest an inclusive evidence of the association between TNF-α-308/ TNF-α-238 G>A and the risk of developing severe dengue infection. Large studies with evidence of Hardy-Weinberg equilibrium, assessing gene-gene interactions are recommended.

Project description:Background and objectiveThe association between TNF-α -308 G/A polymorphism and COPD remains controversial due to insufficiently strict study designs and small group sizes among different studies. In the present study, a meta-analysis update which followed a stricter procedure was performed to obtain a clearer understanding of this association.MethodsA comprehensive database search was conducted to identify the case-control studies published up to July 2015 which reported an association between the TNF-α -308 G/A polymorphism and COPD risk. Data were extracted to calculate pooled odds ratios with 95% confidence intervals under the most appropriate genetic and allelic models. Sensitivity was analyzed, and heterogeneity as well as publication bias was assessed.ResultsThirty-eight eligible studies, comprising 3,951 COPD cases and 5,110 controls, were included in this study, among which 22 studies comprising 2,067 COPD cases and 2,167 controls were performed in Asians, and 16 studies comprising 1,884 COPD cases and 2,943 controls were in non-Asians. The overall result showed that TNF-α -308 G/A polymorphisms were significantly associated with increased COPD risk in both the codominant genetic and allelic models. Individuals with the GA or AA genotype were more susceptible to COPD development than those with the GG genotype. In addition, individuals with the AA genotype were more susceptible to developing COPD than those with the GA genotype. The subgroup analysis stratified by ethnicity supported the results in Asians but not in non-Asians. However, no association was found between TNF-α -308 G/A polymorphisms and COPD susceptibility either in Asians or in non-Asians in the meta-analysis conducted with restriction to former/current smokers.ConclusionThe present meta-analysis suggested that the TNF-α -308 G/A polymorphism was associated with an increased risk of COPD among Asians but not in non-Asians. Furthermore, individuals with the AA genotype of TNF-α -308 were more susceptible to developing COPD.

Dataset Information

The TNF-alpha-238 polymorphism and cancer risk: a meta-analysis.

Publications

The TNF-alpha-238 polymorphism and cancer risk: a meta-analysis.

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