The Relation Between Host TLR9 -1486T/C, rs187084 Gene Polymorphisms and Helicobacter pylori cagA, sodB, hsp60, and vacA Virulence Genes among Gastric Cancer Patients

Sultan, Amira M.; Shenouda, Ragy; Sultan, Ahmed; Shehta, Ahmed; Nabiel, Yasmin

doi:10.33073/pjm-2022-003

Cited by 4 publications

(20 citation statements)

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“…For these studies, only the SNPs that followed the HWE were included in the meta-analysis. Finally, a total of 45 publications ( Zeng et al, 2011a ; de Oliveira and Silva, 2012 ; Castano-Rodriguez et al, 2014 ; Castaño-Rodríguez et al, 2014 ; Companioni et al, 2014 ; Dargiene et al, 2018 ; Eed et al, 2020 ; Gao et al, 2020 ; Li et al, 2021 ; Sultan et al, 2022 ; Garza-Gonzalez et al, 2007 ; Hold et al, 2007 ; Tahara et al, 2007 ; Santini et al, 2008 ; Trejo-de la et al, 2008 ; Hishida et al, 2009 ; Hold et al, 2009 ; Hishida et al, 2010 ; Huang et al, 2010 ; Rigoli et al, 2010 ; Zeng et al, 2011b ; Kupcinskas et al, 2011 ; Schmidt et al, 2011 ; De Oliveira et al, 2013 ; He et al, 2013 ; Kim et al, 2013 ; Wang et al, 2013 ; Huang et al, 2014 ; Kutikhin et al, 2014 ; Li et al, 2014 ; Qadri et al, 2014 ; He et al, 2015 ; Liu et al, 2015 ; Ravishankar Ram et al, 2015 ; Stubljar et al, 2015 ; Wei et al, 2015 ; Mukherjee et al, 2016 ; Simawaranon et al, 2017 ; Xu et al, 2017 ; He et al, 2018a ; De Re et al, 2019 ; Huang et al, 2019 ; Susi et al, 2019 ; Tongtawee et al, 2019 ; de Matos Lourenço et al, 2020 ; Gonzalez-Hormazabal et al, 2021 ), with a total sample size of 25,831 participants (cases: 11,308; controls: 14,523), examining the relation of 18 different SNPs in the TLR family to GC, were eligible to be included in the present meta-analysis. The analyzed studies were published from 2007 to 2022.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, we systematically reviewed the results of the studies on less common SNPs of TLRs and GC that were not eligible for meta-analysis (with only one available effect size) ( Zeng et al, 2011b ; Kim et al, 2013 ; Yang et al, 2013 ; Castano-Rodriguez et al, 2014 ; Companioni et al, 2014 ; Liu et al, 2015 ; De Re et al, 2019 ; Wang et al, 2019 ; Gao et al, 2020 ; Gonzalez-Hormazabal et al, 2021 ; Li et al, 2021 ) to have a comprehensive evaluation. Of the included studies in the meta-analysis, 12 studies were on Caucasian populations ( Hold et al, 2007 ; Santini et al, 2008 ; Hold et al, 2009 ; Rigoli et al, 2010 ; Kupcinskas et al, 2011 ; Companioni et al, 2014 ; Kutikhin et al, 2014 ; Stubljar et al, 2015 ; Dargiene et al, 2018 ; De Re et al, 2019 ; Eed et al, 2020 ; Sultan et al, 2022 ), seven studies were on Latino populations ( Garza-Gonzalez et al, 2007 ; Trejo-de la et al, 2008 ; de Oliveira and Silva, 2012 ; De Oliveira et al, 2013 ; Susi et al, 2019 ; de Matos Lourenço et al, 2020 ; Gonzalez-Hormazabal et al, 2021 ), and 26 studies were on Asian populations. The mean age of participants ranged from 44.6 ± 15.9 to 66.26 ± 16.32 years.…”

Section: Resultsmentioning

confidence: 99%

“…Changes in the host immune elements, such as toll-like receptors (TLRs), may affect the development of GC via their crucial involvement in triggering adaptive and innate immune responses ( Sultan et al, 2022 ). Ten TLRs have been identified on the surfaces of immune cells as well as gastric epithelial cells in humans ( Eed et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…TLR-9 is also expressed aberrantly in GC, and H. pylori DNA could trigger TLR-9-mediated GC cell invasion ( Gao et al, 2020 ). Single-nucleotide polymorphisms (SNPs) within TLR genes may lead to a change in their expression along with dysregulation of their signaling pathways, resulting in disturbed secretion of inflammatory mediators and enabling H. pylori to cause persistent infection and affecting gastric immunopathology and GC susceptibility ( Eed et al, 2020 ; Sultan et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis

Al Othaim,

Al-Hawary,

Alsaab

et al. 2023

Front. Genet.

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Background: An increasing number of studies have suggested the relationship between single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes and gastric cancer (GC) susceptibility; however, the available evidence is contradictory. This meta-analysis aimed to comprehensively evaluate whether the SNPs within the TLR family are related to GC development.Methods: PubMed, Scopus, and China National Knowledge Infrastructure (CNKI) were systematically searched up to May 2023 to obtain the pertinent publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were applied to examine the associations using the random-effects model.Results: A total of 45 studies with 25,831 participants (cases: 11,308; controls: 14,523) examining the relation of 18 different SNPs in the TLR family to GC were analyzed. Variations in TLR-4 rs4986790, TLR-4 rs4986791, TLR-5 rs5744174, and TLR-9 rs187084 were significantly associated with increased risk of GC in different genetic models. No significant association was detected for TLR-2-196 to -174de (Delta22), TLR-2 rs3804100, TLR-4 rs11536889, TLR-4 rs11536878, TLR-4 rs2770150, TLR-4 rs10116253, TLR-4 rs1927911, TLR-4 rs10983755, TLR-4 rs10759932, TLR-4 rs1927914, and TLR-10 rs10004195.Conclusion: These findings indicate that variations in TLR-4, TLR-5, and TLR-9 genes were found to be potential risk factors for GC.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis

Al Othaim,

Al-Hawary,

Alsaab

et al. 2023

Front. Genet.

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“…Eighteen full-text studies were checked, and ten studies were excluded for different reasons. A final of eight studies that assessed the association of TLR 9 polymorphisms (-1486 T/C, -1237 T/C) were eligible for this meta-analysis [ 5 , 14 , 26 – 31 ]. The excluded ten studies and their justifications were provided in Additional file 3 .…”

Section: Resultsmentioning

confidence: 99%

Toll-like receptor 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer: a meta-analysis of genetic association studies

Qyi,

Aung,

Aye

et al. 2023

BMC Cancer

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Background Gastric cancer has a complex aetiology including genetic factors. Individual case-control studies of toll like receptor (TLR) 9 (-1237 T/C, -1486 T/C) polymorphisms in the gastric cancer risk were available, and they showed variation in the findings. Therefore, we performed a meta-analysis to synthesize the evidence on the association between polymorphisms of TLR 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer using data from eligible studies. Methods This study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed. Results Eight case-control studies with 3,644 participants (1914 cases, 1730 controls) were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating (i.e., a score of ≥ 7). TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer (overall: OR = 1.22, 95%CI = 0.90–1.67, I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38–4.09, I2 = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer (overall: OR = 1.4, 95% CI = 0.74–2.64, I2 = 85%; Asian: OR: 1.41, 95% CI = 1.07–1.86, I2 = 0%, non-Asian: OR = 1.18, 95% CI = 0.12–11.76, I2 = 97%). Under the heterozygous model, there was no significant association with the risk of gastric cancer overall or among any ethnic subgroup. Under the homozygous model in the absence of heterogeneity, only the Asian group had a significantly higher risk of gastric cancer (overall, OR = 1.47, 95% CI = 0.76–2.86, I2 = 82%; Asian: OR = 1.54, 95% CI = 1.13–2.1, I2 = 0%; non-Asian: OR = 1.19, 95% CI = 0.1-14.33, I2 = 96%). Under the allele model, a significantly increased risk of gastric cancer was observed only in the Asian group (overall: OR = 1.23, 95% CI = 0.89–1.71, I2 = 84%; Asian: OR = 1.22, 95% CI = 1.05–1.41, I2 = 0%; non-Asian: OR = 1.24, 95% CI = 0.34–4.59, I2 = 97%). Four studies investigated the association between TLR 9 (-1237 T/C) polymorphism and the risk of developing gastric cancer. Under any of the five genetic models, there was no association between TLR 9 (-1237 T/C) and the development of gastric cancer in overall or in any ethnic subgroup. Sensitivity analysis revealed that the effect was unstable. With a small number of studies with a small number of participants, we addressed the issue of insufficient power for drawing conclusions. Conclusions The findings suggested that TLR9 (-1486 T/C) may play a role in the risk of gastric cancer specific to the Asian ethnic group. To substantiate the findings on the association between these two polymorphisms (TLR9 -1237 T/C, -1486 T/C) and the risk of gastric cancer, future well-designed case-control studies with a sufficient number of participants in multi-ethnic groups are recommended.

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Hp0521 inhibited the virulence of H. pylori 26,695 strain via regulating CagA expression

Shen

et al. 2023

Heliyon

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The Relation Between Host TLR9 -1486T/C, rs187084 Gene Polymorphisms and Helicobacter pylori cagA, sodB, hsp60, and vacA Virulence Genes among Gastric Cancer Patients

Cited by 4 publications

References 42 publications

Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis

Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis

Toll-like receptor 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer: a meta-analysis of genetic association studies

Hp0521 inhibited the virulence of H. pylori 26,695 strain via regulating CagA expression

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