Tumor Necrosis Factor Alpha Extended Haplotypes and Risk of Gastric Carcinoma

Canedo, Paulo; Durães, Cecília; Перейра, Фернандо Лобо; Regalo, Gonçalo; Lunet, Nuno; Barros, Henrique; Carneiro, Fátima; Seruca, Raquel; Rocha, Jorge; Machado, José Carlos

doi:10.1158/1055-9965.epi-08-0413

Cited by 34 publications

(19 citation statements)

References 31 publications

(32 reference statements)

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“…None of the polymorphisms identified in the promoter of the TGF-b1 gene in this study corresponded to the homologous position of the TGF-b1 -509 C[T variant identified in humans. A polymorphism identified in the promoter of the human IFN-cR1 gene was found to be associated with increased risk of developing early gastric carcinoma (Canedo et al 2008), and in vitro, this polymorphism (-56T[C) has been shown to alter promoter activity (Rosenzweig et al 2004). Later, in silico analysis predicted an AP-2/AP-4 consensus binding site around position -56 of this gene in humans, explaining the observed effect on promoter activity.…”

Section: Discussionmentioning

confidence: 99%

Identification of polymorphisms in genes of the immune system in cynomolgus macaques

Adkins

2012

Mamm Genome

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Cynomolgus macaques are a standard species used preclinically for evaluating efficacy and toxicity of therapeutic drug candidates and vaccines. However, findings from preclinical studies conducted in cynomolgus macaques are often highly variable, which may in part be attributed to genetic diversity. In this study, genetic polymorphisms were identified in 49 genes of the immune system using DNA isolated from 40 cynomolgus macaques. Of these, 20 originated from a breeding center in China and 20 were of Mauritian origin. A total of 580 polymorphisms were identified, including 561 SNPs, 9 deletions, and 10 insertions with minor allele frequencies ranging from 0.03 to 0.5. Of these genes, 92 % had a SNP distribution frequency >1 per 1,000 bp, illustrating that genes of the immune system in cynomolgus macaques are highly polymorphic. There were 551 common SNPs between the Chinese and Mauritian populations, demonstrating a surprisingly high level of conservation. In silico tools were employed to predict the functional consequences for 264 nonintronic polymorphisms identified. Five polymorphisms were predicted to alter binding of one or more transcription factors, and four were predicted to interfere with miRNA target sites. Additionally, 107 were identified to be nonsynonymous polymorphisms with one causing a frameshift in protein sequence (20,787C deletion in TGF-β1) and three generating premature stop codons (11,990 C>T in IFN-γR2, 11174 C>T in CR1, and 3477 G>T in CTLA-4). Understanding polymorphisms present in cynomolgus macaque genes and their functional consequences will enhance understanding and interpretation of data from preclinical studies conducted in this species.

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Section: Discussionmentioning

confidence: 99%

Identification of polymorphisms in genes of the immune system in cynomolgus macaques

Adkins

2012

Mamm Genome

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“…An association of TNF-α -308G>A (rs1800629) with susceptibility/resistance to GC development has been widely investigated and yielded conflicting results. Studies including GC patients and controls from China (7)(8)(9)(10)(11)(12)(13)(14), Brazil (15,16), Portugal (17,18), United States (19), Poland (20), South Korea (21-23), Honduras (24), Italy (25), Colombia (26), and Japan (27) have been associated with susceptibility to GC development. However, other studies including those from India (28), Brazilian (29,30), Romania (31), Spain (32,33), South Korea (34,35), China (36), Mexico (37), Germany (38) and Finland (39) failed to show a possible link between the TNF-α (-308G>A) polymorphism and GC.…”

Section: Introductionmentioning

confidence: 99%

Role of TNF-α -308G/A gene polymorphism in gastric cancer risk: A case control study and meta-analysis

Du¹,

Gao²

2017

Turk J Gastroenterol

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Background/Aims: In the Chinese population, gastric cancer (GC) is ranked as the third most common type of cancer. Although the exact etiology of GC development is unclear, several factors, including genetic and environmental, have been identified as risk factors. Variations in cytokine genes and their receptors have been related to a higher risk of GC. A single nucleotide polymorphism in the promoter region of tumor necrosis factor-α (TNF-α) (-308G>A) has been associated with a higher risk of GC and in the present study we evaluated its possible association with GC in a Chinese cohort. In addition, we performed a meta-analysis to draw a firm conclusion about the association between TNF-α gene polymorphisms and GC. Materials and Methods: We enrolled 400 Chinese GC patients and matched healthy controls hailing from similar geographical areas. The TNF-α -308G/A polymorphism was genotyped by allele-specific polymerase chain reaction (AS-PCR). For the meta-analysis, earlier published articles were searched and eligible studies were included. Results: Prevalence of the heterozygous mutant (GA) and minor allele (A) were significantly higher in GC cases compared to healthy controls (GA: p<0.0001, odds ratio (OR)=4.90; A: p<0.0001, OR=2.84). A total of 36 eligible studies including the present report, encompassing of 8353 GC patients and 12099 controls, were analyzed for the meta-analysis. A significant association of the TNF-α polymorphism (-308G>A) with susceptibility to GC was only found in the Caucasian population (A vs G: p=0.001; AA vs GG: p=0.01; AG vs GG: p<0.0001; AA vs AG+GG: p=0.01; AA+AG vs p=0.003). Conclusion:The results of the present case control study and meta-analysis showed that associations between TNF-a variants with susceptibility to GC development is population and ethnic specific. Keywords: Gene polymorphism, TNF-α, gastric cancer, meta-analysis, association, Chinese Original ArticleCite this article as: Du LC, Gao R. Role of TNF-α -308G/A gene polymorphism in gastric cancer risk: a case control study and metaanalysis. Turk J Gastroenterol 2017; 28: 272-82.

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“…Over the years, several environmental factors, including diet, tobacco smoking and Helicobacter pylori infection, have been shown to be responsible for gastric carcinogenesis (2,3). Besides environmental factors, genetic factors also play an important role in the development of GC, and this is confirmed by the fact that only a small proportion of individuals exposed to known environmental risk factors develop GC (4,5). Additionally, recent studies have shown that single-nucleotide polymorphisms (SNPs) in genes encoding tumor necrosis factor α, COX-2, and CD14 are associated with increased GC risk (5-7), indicating that genetic variation contributes to GC carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Effect of PSCA gene polymorphisms on gastric cancer risk and survival prediction: A meta-analysis

Zhang

Chen

Wang

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Previous studies have shown that two single-nucleotide polymorphisms (SNPs) in PSCA (rs2976392 and rs2294008) are associated with gastric cancer (GC), but the results are conflicting. Additionally, the prognostic value of PSCA gene polymorphisms for GC patients is unknown. We performed a meta-analysis using 9 eligible case-control studies to investigate the association between PSCA polymorphisms and GC risk, and additionally investigated the prognostic value of PSCA polymorphisms for GC patients with two eligible studies. The association was measured using random-effect or fixed-effect odds ratios (ORs) combined with 95% confidence intervals (CIs) according to the heterogeneity of the studies. We found that rs2294008 (dominant model: OR, 1.44; 95% CI, 1.16-1.79) and rs2976392 (dominant model: OR, 1.41; 95% CI, 0.98-2.04) polymorphisms were associated with increased risk of GC, although the association of rs2976392 was not statistically significant. For rs2294008, the associations were all consistently significant among the different subgroups stratified by ethnicity and tumor location, but not significant in intestinal or diffuse subtypes. For rs2976392, the associations were consistently significant for the intestinal, diffuse and non-cardia subtypes, but not significant for the cardia subtype. Furthermore, two eligible studies reported inverse results of PCSA in predicting the survival of GC patients (HR, 0.75; 95% CI, and HR, 2.12; 95% CI, respectively). In conclusion, PSCA gene polymorphisms are associated with increased risk of GC and are correlated with the prognosis of GC patients. Future studies are required to evaluate the molecular mechanisms of PSCA polymorphisms in GC and validate the prognostic value in a larger number of patients.

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Tumor Necrosis Factor Alpha Extended Haplotypes and Risk of Gastric Carcinoma

Cited by 34 publications

References 31 publications

Identification of polymorphisms in genes of the immune system in cynomolgus macaques

Identification of polymorphisms in genes of the immune system in cynomolgus macaques

Role of TNF-α -308G/A gene polymorphism in gastric cancer risk: A case control study and meta-analysis

Effect of PSCA gene polymorphisms on gastric cancer risk and survival prediction: A meta-analysis

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