Dataset Information

Population differences concerning TNF-α gene polymorphisms in gastric carcinogenesis based on meta-analysis.

ABSTRACT:

Background

Recent meta-analyses have studied population differences concerning interleukin (IL)-1 gene polymorphisms in gastric carcinogenesis. In addition to the IL-1 gene cluster, candidate genes include those encoding the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The aim of the study was to systematically review the role of TNF-α-238 and TNF-α-308 gene polymorphisms (genotypes G/G, G/A, A/A) in gastric carcinogenesis by meta-analyzing all relevant studies to look for any differences concerning TNF-α gene polymorphisms in gastric carcinogenesis.

Methods

Extensive English language medical literature searches for human studies were performed up to the end of May 2013, using suitable keywords. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using the random-effects model. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the adjusted rank correlation test.

Results

In seventeen studies, from various countries, the TNF-α-308 and TNF-α-238 frequencies of genotypes G/G, G/A, A/A were examined in gastric cancer patients and controls. For TNF-α-308 frequency overall, the pooled ORs with 95%CI for genotype G/G, A/A and G/A were 0.837 (0.712-0.982), 1.430 (1.064-1.923) and 1.145 (0.973-1.348) with respective P values 0.029, 0.018 and 0.104. Subgroup analyses showed significant results for genotype G/G only in Asians [OR=0.774 (0.610-0.983), P=0.036].

Conclusion

In this meta-analysis there was an overall statistically significant increased cancer risk associated with TNF-α-308 G/G and A/A genotypes. Subgroup analyses showed significant results for genotype G/G in Asians, whereas no such significant results were found for Caucasians and Hispanics.

SUBMITTER: Rokkas T

PROVIDER: S-EPMC3982629 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Population differences concerning TNF-α gene polymorphisms in gastric carcinogenesis based on meta-analysis.

Rokkas Theodoros T Sechopoulos Panos P Pistiolas Dimitrios D Kothonas Fotis F Margantinis Georgios G Koukoulis Georgios G

Annals of gastroenterology 20140101 2

<h4>Background</h4>Recent meta-analyses have studied population differences concerning interleukin (IL)-1 gene polymorphisms in gastric carcinogenesis. In addition to the IL-1 gene cluster, candidate genes include those encoding the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The aim of the study was to systematically review the role of TNF-α-238 and TNF-α-308 gene polymorphisms (genotypes G/G, G/A, A/A) in gastric carcinogenesis by m ...[more]

PMID: 24733020

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Project description:BackgroundTumor necrosis factor-alpha (TNF-α) is an important cytokine in acute inflammatory response to infective factors. Based on investigation in different populations, it is thought that this response increases in patients with endometriosis due to the presence of cytokines such as TNF-α. This study aimed to examine the association of four TNF-α polymorphisms, namely -238G/A, -308G/A, -857C/T and -863C/A, with susceptibility to endometriosis in an Iranian population.Materials and methodsWe recruited 150 women with endometriosis and 150 women without endometriosis in this case-control study and collected 4 ml of blood from all subjects. After DNA extraction, the polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe allele frequency of TNF-α -863C/A in the case and control groups showed a significant difference [odds ratios (OR)=0.64, 95% confidence interval (CI)=0.41-0.99, P=0.047] but the result is not significant when Adjusting for multiple testing (P=0.188). No significant difference in the allele frequencies of -238G/A (OR=1.07, 95% CI=0.51-2.25, P=0.862), -308G/A (OR=0.79, 95% CI=0.43-1.45, P=0.438) and -857C/T (OR=1.03, 95% CI=0.66- 1.61, P=0.887) was observed. We adjusted all four polymorphism genotypes by age and body mass index (BMI), however, no significant difference was detected. There was an association between the case and control and BMI when adjusting by age (OR=1.082, 95% CI=1.009-1.162, P=0.028).ConclusionFor the first time the association of the four polymorphisms in the promoter region of the TNF-α gene with endometriosis has been conducted in women of Iranian origin. The present research reveals the -863 A allele may play a role in incidence of endometriosis among Iranian women. Development of endometriosis among those people with -863 A allele seems low. According to the results, the current study indicates that there might be a correlation between BMI and progression of endometriosis.

Project description:BACKGROUND:Toll-like receptors (TLRs) are the first line of host defense, and are involved in Helicobacter pylori (H. pylori) recognition and activation of both inflammatory and carcinogenic processes. The presence of single nucleotide polymorphisms (SNPs) in genes that activate the immune response may modulate the risk of precancerous lesions and gastric cancer (GC). Among them, Toll-like receptor 9 (TLR9) polymorphisms have emerged with a risk factor of infectious diseases and cancer, however the studies are still inconclusive. AIM:To evaluate whether TLR9 rs5743836 and rs187084 SNPs contribute to the risk of gastric carcinogenesis, and its influence on mRNA expression. METHODS:A case-control study was conducted to evaluate two TLR9 SNPs (TLR9-1237 TC-rs5743836 and TLR9-1486 CT-rs187084) in chronic gastritis (CG) and GC patients. A total of 609 DNA samples of peripheral blood [248 CG, 161 GC, and 200 samples from healthy individuals (C)] were genotyped by polymerase chain reaction-restriction fragment length polymorphism. All samples were tested for the H. pylori infection using Hpx1 and Hpx2 primers. Quantitative polymerase chain reaction by TaqMan® assay was used to quantify TLR9 mRNA from fresh gastric tissues (48 GC, 26 CG, and 14 C). RESULTS:For TLR9-1237, the TC + CC or CC genotypes were associated with a higher risk of GC than C [recessive model odds ratio (OR) = 5.01, 95% confidence interval (CI): 2.52-9.94, P < 0.0001], and the CG (recessive model OR =4.63; 95%CI: 2.44-8.79, P < 0.0001) groups. For TLR9-1486, an association between the CT + TT genotypes and increased risk of both GC (dominant model OR = 2.72, 95%CI: 1.57-4.72, P < 0.0001) and CG (dominant model OR = 1.79, 95%CI: 1.15-2.79, P = 0.0094) was observed when compared to the C group. Moreover, the presence of TLR9-1237 TC/CC + TLR9-1486 CC genotypes potentiate the risk for this neoplasm (OR = 18.57; 95%CI: 5.06-68.15, P < 0.0001). The TLR9 mRNA level was significantly higher in the GC group (RQ = 9.24, P < 0.0001) in relation to the CG group (RQ = 1.55, P = 0.0010) and normal mucosa (RQ = 1.0). When the samples were grouped according to the polymorphic genotypes and the presence of H. pylori infection, an influence of TLR9-1237 TC + CC polymorphic genotypes (P = 0.0083) and H. pylori infection (P < 0.0001) was observed on the upregulation of mRNA expression. CONCLUSION:Our findings show that TLR9 rs5743836 and rs187084 polymorphisms are associated with a higher risk of carcinogenesis gastric, and that TLR9 mRNA levels can be modulated by TLR9-1237 TC + CC variant genotypes and H. pylori infection.

Project description:BackgroundThe associations between TNF-α and Interleukin gene polymorphisms and polycystic ovary syndrome (PCOS) risk have been studied in numerous epidemiological studies, but the results remain controversial. To investigate whether these polymorphisms facilitate susceptibility to PCOS, we conducted a comprehensive systematic review and meta-analysis.MethodsPubMed, Embase, Web of Science, Medline, CNKI, and Google Scholar were searched to obtain the genetic association studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (OR) with corresponding 95 % confidence intervals (CI) were used to assess the strengths of the associations. Funnel plots and Egger's tests were performed to test for possible publication bias. All statistical analyses were performed using Review Manager 5.2 and STATA11.0.ResultsEighteen articles were included in the final meta-analysis. The studies involved the following polymorphisms: TNF-α -308G > A, TNF-α -805C>T, TNF-α -1031 T>C, IL-1A -889C>T, IL-1B -511C>T, IL-1B +3953 T>C, IL-6 -174G>C, IL-10 -819C>T, IL-10 -1082A>G, IL-18 -607C>A, and IL-18 -137G>C. Our results show a significant association between PCOS risk and the TNF-α -1031 T>C polymorphism (For TC+CC vs. TT: OR=2.09, 95 % CI=1.58-2.76, p<0.0001. For C allele vs. T allele: OR=1.67, 95 % CI=1.33-2.09, p<0.0001) and between PCOS risk and the IL-6 -174>C polymorphism (For CC+GC vs. GG: OR=0.49, 95 % CI=0.25-0.95, p=0.03. For CC vs. GG: OR=0.48, 95 % CI=0.28-0.80, p=0.005. For C vs. G: OR=0.60, 95 % CI=0.42-0.87, p=0.007). No associations were found with the other genetic models.ConclusionThe results of the meta-analysis suggest positive associations between the TNF-α -1031 T>C and IL-6 -174G>C polymorphisms and the risk of PCOS. No associations are found between PCOS risk and the TNF-α -308G>A, TNF-α -805C>T, IL-1A -889C>T, IL-1B -511C>T, IL-1B +3953C>T, IL-10 -819C>T, IL-10 -1082 A>G, IL-18 -607C>A, and IL-18 -137G>C polymorphisms. However, due to the heterogeneity and low quality of the studies related to PCOS polymorphisms in the meta-analysis, the results should be interpreted with caution. Future multi-ethnicity studies of homogeneous populations of PCOS patients with larger sample sizes and well-matched controls are needed.

Dataset Information

Population differences concerning TNF-α gene polymorphisms in gastric carcinogenesis based on meta-analysis.

Background

Methods

Results

Conclusion

Publications

Population differences concerning TNF-α gene polymorphisms in gastric carcinogenesis based on meta-analysis.

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