Profiles of Gene Polymorphisms in Cytokines and Toll-Like Receptors with Higher Risk for Gastric Cancer

Oliveira, Juliana Garcia de; Rossi, Ana Flávia Teixeira; Nizato, Daniela Manchini; Miyasaki, Kenji; Silva, Ana Elizabete

doi:10.1007/s10620-012-2460-5

Cited by 46 publications

(32 citation statements)

References 56 publications

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“…Among the TNF-α-308 G/A and -857 C/T SNPs evaluated in this study, only TNF-α-857 C/T was found to be associated with gastric cancer. Several studies have reported the same association [9,20,[40][41][42][43], but studies attempting to associate cytokine expression with the presence of SNPs are uncommon [7].…”

Section: Discussionmentioning

confidence: 94%

“…Examples of these polymorphisms include IL-1β, IL-1RN, IL-8, TNF-α, and IL-10, which may contribute to variations in the risk of developing gastric cancer [1,[4][5][6]. Some SNPs that occur within regulatory regions of cytokine genes are believed to be involved in changes to the affinity of transcription factors, and they therefore affect the cytokine expression and secretion profile in response to agents of infection [7].…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that the polymorphic allele A of the -251 T/A polymorphism upregulates IL-8 levels after LPS stimulation in vitro [17,18]. The IL-8-845 T/C polymorphism (rs2227532) has received attention from researchers, who have attempted to associate it with inflammatory diseases and cancer [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer

et al. 2015

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Functional polymorphisms in promoter regions can produce changes in the affinity of transcription factors, thus altering the messenger ribonucleic acid (mRNA) expression levels of inflammatory cytokines associated with the risk of cancer development. The goal of this study was to evaluate the influence that polymorphisms in the cytokine genes known as TNF-α-308 G/A (rs1800629), TNF-α-857 C/T (rs1799724), IL-8-251 T/A (rs4073), IL-8-845 T/C (rs2227532), and IL-10-592 C/A (rs1800872) have on changes to mRNA expression levels and on the risks of chronic gastritis (CG) and gastric cancer (GC). A sample of 723 individuals was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Relative mRNA expression levels were measured using quantitative real-time PCR (qPCR). Polymorphisms TNF-α-308 G/A and IL-8-251 A/T were not associated with risks of these gastric lesions. However, TNF-α-857 C/T, IL-8-845 T/C, and IL-10-592 C/A were found to be associated with a higher risk of GC, and IL-10-592 C/A was found to be associated with a higher risk of CG. The relative mRNA expression levels (RQ) of TNF-α, IL-8, and IL-10 were markedly downregulated in the CG group (median RQs = 0.128, 0.247, and 0.614, respectively), while the RQ levels of TNF-α in the GC group were upregulated (RQ = 2.749), but were basal for IL-8 (RQ = 1.053) and downregulated for IL-10 (RQ = 0.179). When the groups were stratified according to wild-type and polymorphic alleles, only for IL-8-845 T/C the polymorphic allele was found to influence the expression levels of this cytokine. IL-8-845 C allele carriers were significantly upregulated in both groups (GC and CG; RQ = 3.138 and 2.181, respectively) when compared to TT homozygotes (RQ = -0.407 and 0.165, respectively). In silico analysis in the IL-8 promoter region revealed that the presence of the variant C allele in position -845 is responsible for the presence of the binding sites for two transcription factors (REL and CREB1), which are involved in increased gene expression. Polymorphic alleles were not shown to have any effect on the expression levels of TNF-α and IL-10. Taken together, our findings provide evidence for an association of TNF-α-857 C/T, IL-8-845 T/C, and IL-10-592 C/A with a higher risk of gastric cancer and also demonstrate the influence that the polymorphic C allele of IL-8-845 has on changes to the gene expression levels of this cytokine.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer

et al. 2015

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“…62 Studies in different populations revealed association between individual's carriers of the allele 2 and increased risk of developing chronic gastritis, gastric ulcer and gastric cancer. 63,64 IL-6 is a pro-inflammatory cytokine that acts as an inflammatory mediator and endocrine regulator, playing an important role in host defense mechanisms as a messenger between innate and adaptive systems. 65 Moreover, it is involved in the regulation of various cellular functions, such as, proliferation, apoptosis and angiogenesis.…”

Section: 7879mentioning

confidence: 99%

Genes de patogenicidade de Helicobacter pylori, polimorfismos de citocinas e fatores ambientais afetam o desenvolvimento de doenças gástricas: uma visão geral

Vianna¹,

Silva²,

Ramis³

2016

Rev Epidemiol Control Infect

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Exceto onde especificado diferentemente, a matéria publicada neste periódico é licenciada sob forma de uma licença Creative Commons -Atribuição 4. pylori possui um conjunto de fatores de patogenicidade, tais como cagA, vacA, iceA, babA, para colonizar a mucosa gástrica e estabelecer infecção crônica. Estes fatores bacterianos são agentes essenciais em modular a resposta imune envolvida na iniciação da carcinogênesegástrica. Os fatores genéticos do hospedeiro contribuem para regular a resposta inflamatória e para o agravamento da lesão da mucosa gástrica uma vez que a infecção gástrica por H. pylori induz a produção de várias citocinas pró e anti-inflamatórias no hospedeiro. O papel prejudicial dos fatores ambientais está relacionado com as precárias condições socioeconômicas, com o consumo de sal, com o tabagismo e com o consumo de álcool. Conclusão: Ao decifrar as regras deterministas -se houver -dessa interação entre fatores da bactéria, do hospedeiro e variáveis ambientais, será possível prever, tratar e, finalmente, prevenir graves doenças gastroduodenais. Background and Objectives:Helicobacter pylori is a Gram-negative bacterium that colonizes the stomach of approximately 50% of the world´s human population. This microorganismis the major causal agent of gastritis and is an important risk factor for the development of peptic ulcer disease and gastric carcinoma. The factors that determine these diverse clinical outcomes are subject to continuous investigations and is thought to be determined by interaction of bacterial factors, host immune system and environmental variables. The aim of this review is to provide an overview of these factors that influence susceptibility to severe outcomes of H. pylori

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“…(2) A population genetics approach Table 3 Genotype and allele frequencies, odds ratio, confidence interval, and p value of the logistic regression analysis with and without the covariates sex, age, Native American ancestry, socioeconomic (first factor), symptoms (second factor), and nutritional (third factor) information, using additive, dominant, and recessive model (3) Although controlling for ancestry is critical for variants that have different allele frequencies in Native Americans, Europeans, and Africans, ancestry (estimated with enough accuracy) is frequently ignored in candidate-gene association studies in Latin American populations [45]. (4) Although we did not find association between the tested SNPs and gastric cancer in the population from Lima with high Native American ancestry, meta-analyses suggest that IL8-rs4073-A and PTGS2-rs689466-A are susceptibility variants for gastric cancer in Asia.…”

Section: Effect Of Promoter Haplotype On Il8rb Transcriptional Activamentioning

confidence: 99%

Population, Epidemiological, and Functional Genetics of Gastric Cancer Candidate Genes in Peruvians with Predominant Amerindian Ancestry

et al. 2015

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Profiles of Gene Polymorphisms in Cytokines and Toll-Like Receptors with Higher Risk for Gastric Cancer

Abstract: Our findings evidenced that the combined effect of polymorphisms in genes involved in the inflammatory process may potentiate the risk of gastric cancer, thus emphasizing the importance of evaluating multiple polymorphisms together.

Cited by 46 publications

References 56 publications

Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer

Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer

Genes de patogenicidade de Helicobacter pylori, polimorfismos de citocinas e fatores ambientais afetam o desenvolvimento de doenças gástricas: uma visão geral

Population, Epidemiological, and Functional Genetics of Gastric Cancer Candidate Genes in Peruvians with Predominant Amerindian Ancestry

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