scholarly journals Polymorphisms of Tumour necrosis factor-α-308 (rs 1800629) and gastric cancer susceptibility: A meta- analysis of associations studies with trial sequential analysis

2021 ◽  
Author(s):  
Norah Htet Htet ◽  
Cho Naing ◽  
Wong Siew Tung ◽  
Thin Thin Win ◽  
Joon Wah Mak
Keyword(s):  
Gastric Cancer ◽  
Sequential Analysis ◽  
Association Studies ◽  
Meta Analysis ◽  
Genetic Association Studies ◽  
Trial Sequential Analysis ◽  
Tnf Α ◽  
Strength Of Association ◽  
Necrosis Factor

Abstract Background: Gastric cancer is globally the fifth most common cancer. Several studies have assessed the relationship between tumour necrosis factor-alpha (TNF-a- 308) and the risk of gastric cancer. These individual genetic association studies showed inconclusive results. The objective of the present study was to synthesis evidence on the association between TNF-a-308 polymorphisms and gastric cancer risk by meta-analysis of data from eligible studies.Methods: We performed a meta-analysis of genetic association studies, according to the PLOS One checklist. We searched relevant case-control studies in health-related electronic databases. The methodological quality of included studies was assessed by the Newcastle-Ottawa quality assessment scale. The strength of association was calculated as odds ratios (ORs) with 95% confidence intervals (CIs). Pooled ORs and 95 % CIs were estimated using random-effects model or fixed effect model, based on between-study heterogeneity. We analysed the strength of association under four genetic models (allele, dominant, recessive and additive models). Subgroup analyses on ethnic groups, Hardy-Weinberg equilibrium (HWE) status, status of Helicobacter pylori infection and study quality were done for robustness of the estimates. Publication bias was detected by inspection of funnel plot asymmetry. To estimate the required information size, we performed trial sequential analysis (TSA) that classified the effect estimates as ‘firm evidence of effect’ or ‘potentially spurious evidence of effect’.Results: A total of 35 studies, comprising 11353 cases and 12827 controls were identified. Based on 28 studies that met HWE, there was overall significant association between TNF-α-308 polymorphisms and gastric cancer risk under the dominant model (OR 1.19, 95%CI 1.1-1.29, I2:37%), as well as Asians (OR 1.2, 95%CI 1.05-1.38, I2:53%) and Cassian subgroups (OR 1.19, 95%CI 1.07-1.31, I2:28%). Based on 13 high quality studies under the dominant model, overall significant association was also found (OR 1.38, 95%CI 1.07, 1.77). The TSA plot indicated the analyses was with the required information size. There was no publication bias. In the subgroup analysis by ethnic groups, the quality of studies impacted on the estimates. Conclusions: The findings suggest that TNF-α-308 gene polymorphism plays an important predisposing role for gastric carcinogenesis, and can serve as a useful screening marker.

scholarly journals Tumour necrosis factor-α(-308) polymorphism and the risk of gastric cancer: A meta- analysis and trial sequential analysis

2019 ◽  
Author(s):  
Cho Naing ◽  
Wong Siew Tung ◽  
Norah Htet Htet ◽  
Kandasami Palayan ◽  
Thin Thin Win ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumour Necrosis ◽  
Association Studies ◽  
Meta Analysis ◽  
Genetic Association Studies ◽  
Gastric Cancer Risk ◽  
Effect Model ◽  
Strength Of Association ◽  
Necrosis Factor

Abstract Background: Numerous studies have reported that polymorphisms in the tumour necrosis factor-alpha (TNF-a-308) gene are implicated in susceptibility to gastric cancer. However, individual genetic association studies that assessed the relationship between TNF-a- 308 and the risk of gastric cancer showed inconclusive results. The objective of this study was to synthesis evidence on the association between polymorphisms in the TNF-a-308 and gastric cancer risk. Methods: This is a meta-analysis of genetic association studies. We searched relevant case-control studies, assessing TNF- 308 polymorphisms and gastric cancer in health-related electronic databases. The methodological quality of included studies was assessed by the Newcastle-Ottawa quality assessment scale. The strength of association was calculated as odds ratios (ORs) with its 95% confidence intervals (CIs). Pooled ORs and 95 % CIs were estimated using random-effect model or fixed effect model, based on between-study heterogeneity. We analysed the strength of association under dominant, recessive, additive and allele models. Multiple subgroup analyses including ethnic groups, HWE status, study quality were done for robustness of the estimates. Publication bias was detected by inspection of funnel plot asymmetry. Results: A total of 33 studies, comprising 7695 patients and 12327 controls were identified. Based on the studies that met HWE, significant association was found between this polymorphisms and gastric cancer risk under dominant model (OR 1.2, 95%CI 1.1-1.3, I 2 :37%), recessive model OR 1.27, 95%CI 1.0-1.62, I 2 :0%) and additive model (OR 1.31, 95%CI 1.08-1.32, I 2 :0%). The TSA plot indicated the analyses was with the required information size. There was no publication bias. In the subgroup analysis by ethnicity, the ethnic groups and the quality of studies had impact on the estimates. Conclusions: The findings suggest that TNF-α-308 gene polymorphism plays an important role as host genetic factor predisposing to gastric carcinogenesis, and it would be useful for a screening marker.

The Role of Tumor Necrosis Factor-α (TNF-α) Polymorphisms in Gastric Cancer: a Meta-Analysis

2021 ◽  
Author(s):  
Maryam Gholamalizadeh ◽  
Samaneh Mirzaei Dahka ◽  
Hadi Sedigh Ebrahim-Saraie ◽  
Mohammad Esmail Akbari ◽  
Azam Pourtaheri ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Meta Analysis ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Genetic Association Studies of Red Blood Cell Transfusion Related Alloimmunization: A Systematic Review and Meta-Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2459-2459
Author(s):  
Jorn Gerritsma ◽  
Ilja Oomen ◽  
Sanne Meinderts ◽  
C. Ellen van der Schoot ◽  
Bart J. Biemond ◽  
...  
Keyword(s):  
Systematic Review ◽  
Genetic Variants ◽  
Screening Tool ◽  
Association Studies ◽  
Data Extraction ◽  
Meta Analysis ◽  
Genetic Association Studies ◽  
Risk Of Bias ◽  
Cell Disease

Introduction: Blood transfusions are an important treatment modality for patients with either acute or chronic onset anemia such as trauma, sickle cell disease, and hematological malignancies. Transfusion poses a risk for alloimmunization, which may lead to potentially lethal transfusion reactions. A promising strategy to prevent alloimmunization is extensive matching on blood groups, yet this is a costly procedure and should be reserved for patients at highest risk for alloimmunization. Identification of genetic variants that increase the risk for alloimmunization might help to identify high-risk patients and could be used as a screening tool for patients receiving multiple transfusions. Objectives: To summarize all available evidence on genetic risk factors for alloimmunization after blood transfusion. Design: Systematic review with meta-analysis of observational studies. Studies were only included in the meta-analysis if polymorphisms were tested at least 3 times, and if ethnic background of the population and the control populations were comparable between studies. Data sources: The online databases Embase, MEDLINE and the Cochrane Library were search for relevant articles with search terms: 1) transfusion, 2) alloimmunization 3) genetics. The search was last updated March 2018. Eligibility criteria: 1) Primary study that assessed the association of genetic polymorphisms with transfusion related alloimmunization, 2) a human population, 3) studies with at least 50 patients, 4) full text availability. Data extraction: Two reviewers independently screened articles for eligibility, extracted data using a standardized data extraction form. Extracted data included study setting, study population, participant demographics, baseline characteristics, study methodology, comparisons and outcome, and risk of bias. Primary outcome measure: Alloimmunization after one or more blood transfusions. Risk of bias assessment: The quality of the included studies was assessed by the Q-genie tool for genetic association studies. Results: A total of 2045 cases and 24084 controls were derived from 18 genetic case-control studies that were included in this systematic review. Most commonly studied disease group was sickle cell disease (SCD) (8 studies). Three studies included patients with different diseases and seven studies did not report the underlying disease. Eleven studies identified the association of HLA polymorphisms with alloimmunization and 8 studies focused on non-HLA variants. Overall quality of the included studies was moderate (11 studies), 2 studies were of high quality, and 5 studies were ranked as poor. HLA-DRB1*04 (Odds Ratio 7.16, 95%CI 3.87-13.22, P<0.00001) and HLA-DRB1*15 (OR 3.01, 95%CI 1.84-5.53, P<0.0001) were by meta-analysis significantly associated with anti-Fy(a) formation, although there was considerable heterogeneity (I2=78% and 55% respectively). Moreover, HLA-DRB1*10 (OR 2.64, 95%CI 1.41-4.95, P=0.002), HLA*DRB1*11 (OR 2.11, 95%CI 1.34-3.32, P=0.001), and HLA-DRB1*13 (OR 1.71, 95%CI 1.26-2.33, P=0.0006) were overall associated with anti-Kell formation. Heterogeneity was less prominent with an I2 of 0%, 54% and 19% respectively (Figure 1). No other variants were eligible for meta-analysis. Non-HLA variants were tested less extensively, as most variants were reported by only 1 study. Polymorphisms of genes in the immunomodulatory pathways were assessed most frequently. Of these variants, FC-gamma-receptor 2C.nc-ORF was associated with a decreased risk of alloimmunization in SCD (OR 0.26, 95%CI 0.11-0.64, p=0.003). All other associations that were described as significant by the original articles were summarized in Figure 2. Discussion: There is limited evidence supporting the role of genetic risk factors for alloimmunization. The results of our meta-analysis suggest that several HLA polymorphisms potentially influence antigen presentation of the Duffy(a) and Kell antigen. Once confirmed by experimental studies, these polymorphisms could be used as a screening tool for the prevention of alloimmunization among frequently transfused patients. Overall, the effect of genetic variants on alloimmunization has mostly been assessed by small studies, hampering reliable interpretation of the results. Future studies should include large and well-defined cohorts when performing genetic analysis on this complicated subject. Disclosures No relevant conflicts of interest to declare.

scholarly journals Traction Therapy for Cervical Radicular Syndrome is Statistically Significant but not Clinically Relevant for Pain Relief. A Systematic Literature Review with Meta-Analysis and Trial Sequential Analysis

2020 ◽  
Vol 9 (11) ◽  
pp. 3389
Author(s):  
Claudio Colombo ◽  
Stefano Salvioli ◽  
Silvia Gianola ◽  
Greta Castellini ◽  
Marco Testa
Keyword(s):  
Sequential Analysis ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Treatment Modalities ◽  
Trial Sequential Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Quality Of Evidence ◽  
Radicular Syndrome

Aim: We aimed to investigate the effectiveness of traction therapy in reducing pain by performing a systematic review with meta-analysis. We also explore the best modality for administering traction to patients with cervical radicular syndrome (CRS). Methods: We searched the Medline, Physiotherapy Evidence Database (PEDro), Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) electronic databases. Two reviewers independently selected randomized controlled trials (RCTs) that compared traction in addition to other treatments versus the effectiveness of other treatments alone for pain outcome. We calculated the mean differences (MDs) and 95% confidence intervals (CIs). We used Cochrane’s tool to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate the quality of evidence and summarize the study conclusions. Results: A total of seven studies (589 patients), one with low risk of bias, were evaluated. An overall estimate of treatment modalities showed low evidence that adding traction to other treatments is statistically significant (MD −5.93 [95% CI, −11.81 to −0.04] P = 0.05 and I2 = 57%) compared to other treatments alone. The subgroup analyses were still statistically significant only for mechanical and continuous modalities. Conclusions: Overall analysis showed that, compared to controls, reduction in pain intensity after traction therapy was achieved in patients with cervical radiculopathy. However, the quality of evidence was generally low and none of these effects were clinically meaningful.

-308 G > A of TNF-α gene promoter decreases the risk of multiple sclerosis: a meta-analysis

2010 ◽  
Vol 17 (6) ◽  
pp. 658-665 ◽  
Author(s):  
Yan Yang ◽  
Rulin Sun ◽  
Heng Yang ◽  
Fang Zheng ◽  
Feili Gong
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Factors ◽  
Association Studies ◽  
Meta Analysis ◽  
Low Frequency ◽  
Gene Promoter ◽  
Tnf Α ◽  
Control Association ◽  
Necrosis Factor ◽  
Reduced Risk

Background: Environmental and genetic factors are thought to be involved in the pathogenesis of multiple sclerosis (MS). Polymorphisms of tumor necrosis factor (TNF)-α −308 were implicated in MS risk in several case–control association studies. However, the studies have shown inconsistent results. Objectives: To address the association of G/A polymorphisms of TNF-α −308 with MS risk by meta-analysis. Methods: Thirteen studies were included. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated. Results: A total of 1870 cases and 2769 controls were included in the meta-analysis. The pooled result indicated that −308 A allele is significantly associated with reduced risk of MS compared with −308 G allele (A vs. G, p = 0.022). The same pattern of the result was also obtained in the contrasts of AA + GA vs. GG ( p = 0.008) and GA vs. GG ( p = 0.007). For AA vs. GG or AA vs. GA + GG, no significant association was detected most likely caused by very low frequency or non-availability of homozygote genotype AA for all of the studies. Conclusions: TNF-α −308 A allele is associated with reduced risk of MS.

scholarly journals The Effects of Ascorbic Acid Over Sepsis: Meta-analysis With Trial Sequential Analysis

2020 ◽  
Author(s):  
Ying Wang ◽  
Hui-chang Zhuo ◽  
Jiandong Lin
Keyword(s):  
Odds Ratio ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
Random Errors ◽  
Quality Of Evidence ◽  
Randomized Controlled ◽  
Registration Number ◽  
Summary Odds Ratio

Abstract Background: This meta-analysis is performed to evaluate the effects of AA on the mortality over sepsis patients, focusing on the courses and initiation of treatment as well as AA doses.Methods: Randomized controlled trials concerning sepsis patients treated with intravenous AA were included when searching the database. The meta-analysis was performed using the random (M-H heterogeneity) model to produce summary odds ratio with 95% CI. Trial sequential analysis was applied to evaluated the effect of random errors.Results: The included 12 trials enrolled a total of 1232 patients. Intravenously administration of AA could not lower 28-day mortality over sepsis patients (OR = 0.81; 95% CI (0.54-1.23); p = 0.326). Subgroup analysis demonstrated that when administrating AA alone, in a dose ≥ 10 g/d, or within 6 h of admission, the result may turn to positive (OR = 0.36; 95% CI (0.15-0.86); p = 0.020, OR = 0.50; 95% CI (0.27-0.92); p = 0.025, OR = 0.49; 95% CI (0.27-0.89); p = 0.019, relatively). The quality of evidence is moderate.Conclusion: IV AA may have no effects to lower mortality over sepsis patients. However, when administrating AA alone, in a dose ≥ 10 g/d, or within 6 h of admission, the result may turn to positive. Due to a moderate GRADE certainty of evidence, further studies are required to fully elaborate the effectiveness of AA during the management of the sepsis patients.PROSPERO registration number: CRD 42020170825. 24 Feb, 2020 retrospectively registered.

scholarly journals Ivabradine added to usual care in patients with heart failure: a systematic review with meta-analysis and trial sequential analysis

2021 ◽  
pp. bmjebm-2021-111724
Author(s):  
Mathias Maagaard ◽  
Emil Eik Nielsen ◽  
Naqash Javaid Sethi ◽  
Ning Liang ◽  
Si-Hong Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Usual Care ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Trial Sequential Analysis ◽  
Serious Adverse Events ◽  
All Cause Mortality

ObjectivesTo assess the beneficial and harmful effects of adding ivabradine to usual care in participants with heart failure.DesignA systematic review with meta-analysis and trial sequential analysis.Eligibility criteriaRandomised clinical trials comparing ivabradine and usual care with usual care (with or without) placebo in participants with heart failure.Information sourcesMedline, Embase, CENTRAL, LILACS, CNKI, VIP and other databases and trial registries up until 31 May 2021.Data extractionPrimary outcomes were all-cause mortality, serious adverse events and quality of life. Secondary outcomes were cardiovascular mortality, myocardial infarction and non-serious adverse events. We performed meta-analysis of all outcomes. We used trial sequential analysis to control risks of random errors, the Cochrane risk of bias tool to assess the risks of systematic errors and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of the evidence.ResultsWe included 109 randomised clinical trials with 26 567 participants. Two trials were at low risk of bias, although both trials were sponsored by the company that developed ivabradine. All other trials were at high risk of bias. Meta-analyses and trial sequential analyses showed that we could reject that ivabradine versus control reduced all-cause mortality (risk ratio (RR)=0.94; 95% CI 0.88 to 1.01; p=0.09; high certainty of evidence). Meta-analysis and trial sequential analysis showed that ivabradine seemed to reduce the risk of serious adverse events (RR=0.90; 95% CI 0.87 to 0.94; p<0.00001; number needed to treat (NNT)=26.2; low certainty of evidence). This was primarily due to a decrease in the risk of ‘cardiac failure’ (RR=0.83; 95% CI 0.71 to 0.97; p=0.02; NNT=43.9), ‘hospitalisations’ (RR=0.89; 95% CI 0.85 to 0.94; p<0.0001; NNT=36.4) and ‘ventricular tachycardia’ (RR=0.59; 95% CI 0.43 to 0.82; p=0.001; NNT=212.8). However, the trials did not describe how these outcomes were defined and assessed during follow-up. Meta-analyses showed that ivabradine increased the risk of atrial fibrillation (RR=1.19; 95% CI 1.04 to 1.35; p=0.008; number needed to harm (NNH)=116.3) and bradycardia (RR=3.95; 95% CI 1.88 to 8.29; p=0.0003; NNH=303). Ivabradine seemed to increase quality of life on the Kansas City Cardiomyopathy Questionnaire (KCCQ) (mean difference (MD)=2.92; 95% CI 1.34 to 4.50; p=0.0003; low certainty of evidence), but the effect size was small and possibly without relevance to patients, and on the Minnesota Living With Heart Failure Questionnaire (MLWHFQ) (MD=−5.28; 95% CI −6.60 to −3.96; p<0.00001; very low certainty of evidence), but the effects were uncertain. Meta-analysis showed no evidence of a difference between ivabradine and control when assessing cardiovascular mortality and myocardial infarction. Ivabradine seemed to increase the risk of non-serious adverse events.Conclusion and relevanceHigh certainty evidence shows that ivabradine does not seem to affect the risks of all-cause mortality and cardiovascular mortality. The effects on quality of life were small and possibly without relevance to patients on the KCCQ and were very uncertain for the MLWHFQ. The effects on serious adverse events, myocardial infarction and hospitalisation are uncertain. Ivabradine seems to increase the risk of atrial fibrillation, bradycardia and non-serious adverse events.PROSPERO registration number: CRD42018112082.

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