Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) Gene Polymorphism (rs3087243) Is Related to Risk and Survival in Patients With Colorectal Cancer.

ABSTRACT:

Background/aim

Cytotoxic T-lymphocyte antigen-4 (CTLA-4), transiently expressed on T cells, plays a pivotal role in the negative feedback regulation of T-cell activation and proliferation. The aim of the present study was to examine the influence of CTLA-4 gene polymorphism rs3087243 on CRC susceptibility and long-term survival in Swedish patients with CRC.

Patients and methods

Genotypes of 491 patients and 433 healthy controls were determined, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction.

Results

Patients carrying allele A were found to be at a higher risk of CRC and this allele was found to be more common in patients with disseminated disease compared to localized disease in the right colon. Kaplan-Meier analysis of cancer-specific survival showed that carriers of allele A had the highest risk of CRC-related death.

Conclusion

The SNP rs3087243 of the CTLA-4 gene was associated with CRC risk and, therefore, it could be a prognostic marker for Swedish patients with CRC.

SUBMITTER: VAN Nguyen S

PROVIDER: S-EPMC8045117 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Association between cytotoxic T-lymphocyte antigen-4 +49A/G polymorphism and colorectal cancer risk: a meta-analysis.

Project description:The Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) gene has been implicated in the development of colorectal cancer (CRC). However, the results are inconsistent. In this study, we performed a meta-analysis to assess the associations between the CTLA-4 +49A/G polymorphism and risk of CRC. Relevant studies were identified using PubMed, Web of Science, CNKI and WanFang databases up to November 10, 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association using the fixed or random effect model. A total of 8 case-control studies, including 1180 cases and 2110 controls, were included. Overall, a significant association between the CTLA-4 +49A/G polymorphism and CRC risk was found (dominant model: OR=1.63, 95% CI: 1.09-2.43; AG vs. AA: OR=1.69, 95% CI: 1.15-2.48). In the subgroup analysis by ethnicity, we observed a significant association in Asian descent (dominant model: OR=2.42, 95% CI: 1.40-4.16; AG vs. AA: OR=2.39, 95% CI: 1.52-3.76), but not among Europeans; when stratified by source of control, no significant association was detected in both population-based and hospital-based populations. This meta-analysis demonstrated that the CTLA-4 +49A/G polymorphism significantly increases the risk of CRC, especially for Asians.

| S-EPMC4443105 | biostudies-literature

Association between rs3087243 and rs231775 polymorphism within the cytotoxic T-lymphocyte antigen 4 gene and Graves' disease: a case/control study combined with meta-analyses.

Project description:We conducted a case/control study to assess the impact of SNP rs3087243 and rs231775 within the CTLA4 gene, on the susceptibility to Graves' disease (GD) in a Chinese Han dataset (271 cases and 298 controls). The frequency of G allele for rs3087243 and rs231775 was observed to be significantly higher in subjects with GD than in control subjects (p = 0.005 and p = 0.000, respectively). After logistic regression analysis, a significant association was detected between SNP rs3087243 and GD in the additive and recessive models. Similarly, association for the SNP rs231775 could also be detected in the additive model, dominant model and recessive model. A meta-analysis, including 27 published datasets along with the current dataset, was performed to further confirm the association. Consistent with our case/control results, rs3087243 and rs231775 showed a significant association with GD in all genetic models. Of note, ethnic stratification revealed that these two SNPs were associated with susceptibility to GD in populations of both Asian and European descent. In conclusion, our data support that the rs3087243 and rs231775 polymorphisms within the CTLA4 gene confer genetic susceptibility to GD.

| S-EPMC5746408 | biostudies-literature

Association between the cytotoxic T-lymphocyte antigen 4-318C/T polymorphism and malignant tumor risk.

Project description:The cytotoxic T-lymphocyte antigen 4 (CTLA-4) polymorphic loci -318 cytosine/thymine (-318C/T) has been previously implicated in malignant tumor susceptibility. However, there were no precise conclusions about the correlation, the results from published studies were inconclusive. The aim of the current meta-analysis was to investigate the associations between CTLA-4 -318C/T polymorphisms and risk of malignant tumors in Asian population. We conducted a search in PubMed, Embase, the Chinese Journals Full-Text Database, Chinese Biomedical Database, and the Wanfang database. All studies were published up to September 30, 2015. Two reviewers analysed the data independently. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. In total, 20 case-controlled studies with 3,539 cases and 4,690 controls were included in the final meta-analysis. The overall estimation demonstrated a significant association between CTLA-4 -318C/T polymorphism and malignant tumor risk in the Asian populations (TT+TC vs. CC: OR, 1.28; 95% CI, 1.07-1.53. TT vs. TC+CC: OR, 1.43; 95% CI, 1.03-1.99; TT vs. CC: OR, 1.51; 95% CI, 1.09-2.10. TC vs. CC: OR, 1.26; 95% CI, 1.06-1.50. T vs. C: OR, 1.25, 95% CI, 1.05-1.47). In the subgroup analysis by countries, we found that the dominant model (TT+TC vs. CC) revealed an increased risk of developing malignant tumors in the Chinese study population (OR, 1.41; 95% CI, 1.13-1.76), but no association was demonstrated in the other countries. The current meta-analysis suggests that CTLA-4 -318C/T polymorphism is significantly associated with the risk of malignance tumors in Asian populations, especially in those from China. Further studies for additional Asian countries are required to further evaluate the association.

| S-EPMC4907029 | biostudies-other

Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor triggering.

Project description:The inhibitory T-cell surface-expressed receptor, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which belongs to the class of cell surface proteins phosphorylated by extrinsic tyrosine kinases that also includes antigen receptors, binds the related ligands, B7-1 and B7-2, expressed on antigen-presenting cells. Conformational changes are commonly invoked to explain ligand-induced "triggering" of this class of receptors. Crystal structures of ligand-bound CTLA-4 have been reported, but not the apo form, precluding analysis of the structural changes accompanying ligand binding. The 1.8-Å resolution structure of an apo human CTLA-4 homodimer emphasizes the shared evolutionary history of the CTLA-4/CD28 subgroup of the immunoglobulin superfamily and the antigen receptors. The ligand-bound and unbound forms of both CTLA-4 and B7-1 are remarkably similar, in marked contrast to B7-2, whose binding to CTLA-4 has elements of induced fit. Isothermal titration calorimetry reveals that ligand binding by CTLA-4 is enthalpically driven and accompanied by unfavorable entropic changes. The similarity of the thermodynamic parameters determined for the interactions of CTLA-4 with B7-1 and B7-2 suggests that the binding is not highly specific, but the conformational changes observed for B7-2 binding suggest some level of selectivity. The new structure establishes that rigid-body ligand interactions are capable of triggering CTLA-4 phosphorylation by extrinsic kinase(s).

| S-EPMC3057841 | biostudies-literature

Association among cytotoxic T-lymphocyte antigen 4 gene, rs231775 polymorphism, and recurrent pregnancy loss risk.

Project description:Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is expressed constitutively on regulatory T cells. So far, several studies have focused on association between CTLA-4 gene polymorphisms and recurrent pregnancy loss (RPL). However, above association between the CTLA-4 gene polymorphism and RPL susceptibility is uncertain. Therefore, we performed a timely meta-analysis of all current publications to clarify this relationship. We located articles from the PubMed and Chinese language (WanFang) databases that were published up until July 25, 2018. Finally, we obtained six case-control studies, containing 2405 total cases and 2607 total controls, based on search criteria for abortion susceptibility related to the CTLA-4 +49 G/A polymorphism. The odds ratios (OR) and 95% confidence intervals (CIs) revealed association strengths. There was significantly decreased association between this polymorphism and whole population risk (e.g. AA vs. GG: OR = 0.56, 95% CI = 0.38-0.81, P=0.002). Additionally, in ethnicity subgroups, similar association was found both in China (e.g. AA vs. GG: OR = 0.49, 95% CI = 0.39-0.63, P=0.002) and non-China (e.g. AG vs. GG: OR = 0.46, 95% CI = 0.34-0.63, P<0.001). Current analysis suggested CTLA-4 +49 G/A polymorphism may weakly decrease RPL risk for women of childbearing age.

| S-EPMC6356036 | biostudies-literature

Lack of association between cytotoxic T-lymphocyte antigen 4 (CTLA-4) -1722T/C (rs733618) polymorphism and cancer risk: from a case-control study to a meta-analysis.

Project description:BackgroundThe association between cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene -1722T/C polymorphism (rs733618) and cancer has been widely assessed, and a definitive conclusion remains elusive. We first performed a hospital based case-control study to measure this association of esophageal cancer with CTLA-4 -1722T/C polymorphism in Han Chinese population, and then carried out a meta-analysis to obtain a comprehensive evaluation for this issue.Methodology/principal findingsThis case-control study involved 629 esophageal squamous cell carcinoma (ESCC) cases and 686 age and gender well matched cancer-free controls. PCR-LDR (polymerase chain reaction-ligase detection reactions) method was used to identify genotypes. Meta-analysis was conducted by STATA (v12.0) software. This case-control study showed no significant difference in the genotype and allele distributions of CTLA-4 -1722T/C polymorphism between esophageal cancer cases and control subjects, in accord with the findings of the further meta-analysis in all genetic models. Evidence of large heterogeneity was observed among all eligible studies in the recessive model. Further subgroup analyses by ethnicity, cancer type and system, detected null associations in this meta-analysis.ConclusionThis case-control study and the further meta-analysis, failed to identify the association between CTLA-4 -1722T/C polymorphism and cancer risk.

| S-EPMC3978075 | biostudies-literature

Impact of the cytotoxic T-lymphocyte associated antigen-4 rs231775 A/G polymorphism on cancer risk.

Project description:BackgroundCytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is an immunosuppressive checkpoint that is involved in the development and metastasis of cancers. Several studies revealed that CTLA-4 rs231775A/G polymorphism may be associated with the risk of cancer in some populations, but the conclusions of these studies are not consistent.MethodsWe conducted a pooled analysis with eligible studies to explore the association between the CTLA-4 rs231775 variant and cancer risk. Additionally, we used in silico tools to evaluated the expression of CTLA-4 on urinary system cancer. Moreover, we adopted the enzyme-linked immunosorbent assay (ELISA), and Gene Set Enrichment Analysis (GSEA) to investigate the effects of CTLA-4 on bladder cancer (BLCA).ResultsIn total, 92 case-control studies involving 29,987 patients with cancer and 36,484 healthy individuals (controls) were included in the pooled analysis. In the stratified analysis based on cancer type, the rs231775 A/G polymorphism was associated with increased bladder cancer risk in the heterozygote contrast model (OR = 1.23, 95% CI = 1.01-1.51, P = 0.040). The race-stratified analysis revealed that East Asians with the GG genotype had a 12% lower risk of developing cancer than those with the GA + AA genotype (95% CI = 0.81-0.95, P = 0.001). The in silico analysis showed that CTLA-4 expression was augmented in patients with BLCA. The ELISA results revealed that CTLA-4 expression was reduced in patients with BLCA carrying the AA genotype. Several signaling pathways, including cytokine-cytokine receptor interactions and T-cell receptor signaling, were associated with CTLA-4 expression.ConclusionThe CTLA-4 rs231775 A/G polymorphism is associated with cancer risk in East Asian population. This polymorphism is especially associated with BLCA.

| S-EPMC10746491 | biostudies-literature

Expression of immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4), and CD137 in cervical carcinoma.

Project description:Immune checkpoint inhibitors have a significant role in oncology. One of these immune checkpoints is cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Inhibition of the CTLA-4 pathway has already led to the FDA approval of Ipilimumab (anti-CTLA-4), a targeted therapy for melanoma and other malignancies. CD137 is an inducible, costimulatory receptor of the tissue-necrosis-factor-receptor superfamily expressed on the activated immune cells. Clinical trials have also been set for anti-CD137 in several malignancies. We assessed CTLA-4 and CD137 expression on a tissue microarray (TMA) comprising of 99 core tissues which included normal, non-neoplastic, and neoplastic cervical lesions. When detected as strong granular cytoplasmic reaction in the epithelial cells, CTLA-4 expression was scored as positive. For CD137, the results were recorded based on the presence or absence of staining reaction on the cell membranes of the lymphoplasmacytic infiltrates. Overall, CTLA-4 was positive in 30% (30/100) of the cervical malignancies. Sub-categorically, 20% of invasive endocervical adenocarcinomas, 63% of adenosquamous carcinomas, and 31% of squamous cell carcinomas were positive for CTLA-4 with a tendency toward lower grade squamous cell carcinomas (SCCs). CD137 was positive in 100% lymphoplasmacytic infiltrates of endocervical adenocarcinomas, 90.5% of SCCs, and 87.5% of adenosquamous carcinomas. This study has found a significant expression of CTLA-4 in cervical cancer cells and CD137 positivity of lymphoplasmacytic infiltrates with potential for future targeted immunotherapy.

| S-EPMC8569305 | biostudies-literature

Association between Cytotoxic T-lymphocyte antigen 4 (CTLA-4) +49 G>A (rs231775) polymorphism and esophageal cancer: from a case-control study to a meta-analysis.

Project description:The aim of this study was to evaluate the association between CTLA-4 +49 G>A polymorphism and esophageal cancer (EC) susceptibility in a hospital based case-control study and a subsequent meta-analysis. We implemented genotyping analyses for CTLA-4 +49 G>A polymorphism with 629 esophageal squamous cell carcinoma cases and 686 controls in a Chinese Han population. Polymerase chain reaction ligase detection reaction (PCR-LDR) method was used to identify genotypes of CTLA-4 +49 G>A polymorphism. We first assessed the association between CTLA-4 +49 G>A polymorphism and EC risk in a hospital based case-control study, and then performed a comprehensive meta-analysis to derive a more precise estimation. Our results demonstrated that CTLA-4 +49 G>A polymorphism was not associated with EC risk. This case-control study and further meta-analysis, failed to identify the association between CTLA-4 +49 G>A polymorphism and EC risk. And additional, further well designed studies with large sample sizes and detailed gene-environment data are required.

| S-EPMC4694256 | biostudies-literature

CTLA-4-mediated posttranslational modifications direct cytotoxic T-lymphocyte differentiation.

Project description:The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8+ T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization. PDCD4 further bound a distinct set of mRNAs including Glutaminase, which points out a critical role for CTLA-4 in CD8+ T-cell metabolism. Consequently, PDCD4-deficient cytotoxic T-lymphocytes (CTLs) expressed increased amounts of otherwise repressed effector molecules and ultimately led to superior control of tumor growth in vivo. These findings reveal a novel CTLA-4-mediated pathway to attenuate CTLs and indicate the importance of post-transcriptional mechanisms in the regulation of anti-tumor immune responses.

| S-EPMC5596418 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data