The effect of CTLA-4 and CD28 gene variants and circulating protein levels in patients with gastric cancer

Arıkan, Soykan; Gümüş, Alper; Küçükhüseyin, Özlem; Coşkun, Cihan; Turan, Saime; Cacina, Canan; Talu, Canan Kelten; Akyüz, Filiz; Farooqı, Ammad Ahmad; Kıran, Bayram; Yaylım, İlhan

doi:10.1515/tjb-2017-0024

Cited by 8 publications

(3 citation statements)

References 43 publications

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“…The basic information and quality evaluation (NOS) results included in the study are shown in Table 1 . The included studies looked at cancer patients in Asia (n=6) [ 9 , 12 , 13 , 21 , 29 , 30 ] and Caucasians (n=13) [ 14 , 15 , 18 – 20 , 22 – 28 , 31 ]. In addition, in terms of cancer types, leukemia (n=2) [ 12 , 26 ], breast cancer (n=3) [ 9 , 13 , 15 ], colorectal cancer (n=3) [20,27,30)], cervical cancer (n=4) [ 21 – 23 , 28 ], and other cancers (prostate cancer, gastric cancer, renal cell carcinoma, non-small-cell lung cancer, melanoma, myeloma, lymphoma) were included in studies [ 4 , 9 , 14 , 18 , 25 , 29 , 31 ].…”

Section: Resultsmentioning

confidence: 99%

Association Between the CD28 c.17 +3 T>C Polymorphism (rs3116496) and Cancer Risk: An Updated Meta-Analysis

Zeng

Lai

2019

Med Sci Monit

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BackgroundNumerous studies have been conducted on whether CD28 rs3116496 polymorphism affected cancer susceptibility, and these findings have been controversial. Thus, the purpose of this study was to assess the relationship between rs3116496 and susceptibility to cancer.Material/MethodsThe research published as of October 25, 2018 were comprehensively searched in PubMed, Embase, Cochrane Library and Chinese Wanfang database, CNKI, CBM. Statistical calculations performed using Stata12.0.ResultsOverall analyses found that rs3116496 was a risk factor for cancer (C versus T, OR=1.14, 95% CI: 1.01–1.29, PH=0.003), and the heterogeneity was moderate (I2=53.3%). In subgroup analysis results by cancer types, the analysis showed that rs3116496 was a risk factor for breast cancer and leukemia. In the subgroup analysis by ethnicity, rs3116496 was a risk factor for cancer in the Asian population. After PHWE<0.05 was deleted, the analysis showed that rs3116496 might be related to the increased risk of colorectal cancer.ConclusionsOur meta-analysis confirmed that rs3116496 was significantly related to cancer risk, especially in an Asian population, and was strongly correlated with the increased risk of breast cancer, leukemia and colorectal cancer.

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Section: Resultsmentioning

confidence: 99%

Association Between the CD28 c.17 +3 T>C Polymorphism (rs3116496) and Cancer Risk: An Updated Meta-Analysis

Zeng

Lai

2019

Med Sci Monit

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“…Conversely, a study performed in Iran did not find statistically significant differences in the genotype distribution and allele frequencies among CRC patients and controls [ 56 ]. In addition, in a Turkish population showed no significant association between rs231775 and the risk of gastric cancer [ 57 ]. Two meta-analyses found similar results regarding the rs231775 variant, showing an associated risk for cancer development even through subgroup analysis by type and ethnicity suggesting that CTLA-4 rs231775 is a key variant that could be associated with cancer development [ 58 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence of Association between CTLA-4 Gene Polymorphisms and Colorectal Cancers in Saudi Patients

Alharbi

Abdulla

Vaali-Mohammed

et al. 2023

Genes

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Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1) Objective: To explore the association between CTLA-4 single nucleotide polymorphisms (SNP) and risk to (CRC) in the Saudi population. (2) Methods: In this case-control study, 100 patients with CRC and 100 matched healthy controls were genotyped for three CTLA-4 SNPs: rs11571317 (−658C > T), rs231775 (+49A > G) and rs3087243 (CT60 G > A), using TaqMan assay method. Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) for five inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). Furthermore, CTLA-4 expression levels were evaluated using quantitative real-time PCR (Q-RT-PCR) in colon cancer and adjacent colon tissues. (3) Results: Our result showed a significant association of the G allele (OR = 2.337, p < 0.0001) and GG genotype of the missense SNP +49A > G with increased risk of developing CRC in codominant (OR = 8.93, p < 0.0001) and recessive (OR = 16.32, p < 0.0001) models. Inversely, the AG genotype was significantly associated with decreased risk to CRC in the codominant model (OR = 0.23, p < 0.0001). In addition, the CT60 G > A polymorphism exhibited a strong association with a high risk of developing CRC for the AA genotype in codominant (OR = 3.323, p = 0.0053) and in allele models (OR = 1.816, p = 0.005). No significant association was found between −658C > T and CRC. The haplotype analysis showed that the G-A-G haplotype of the rs11571317, rs231775 and rs3087243 was associated with high risk for CRC (OR = 57.66; p < 0.001). The CTLA-4 mRNA gene expression was found significantly higher in tumors compared to normal adjacent colon samples (p < 0.001). (4) Conclusions: Our findings support an association between the CTLA-4 rs231775 (+49A > G) and rs3087243 (CT60 G > A) polymorphisms and CRC risk in the Saudi population. Further validation in a larger cohort size is needed prior to utilizing these SNPs as a potential screening marker in the Saudi population.

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“…CTLA4 is a negative regulator of T-cell function and modulates the duration and strength of T cell mediated immune responses through several intrinsic and extrinsic mechanisms, triggering anergy and immune tolerance (27,28). Several studies have reported significant associations between frequent CTL4 polymorphisms and cancer susceptibility, including CRC (11,(29)(30)(31)(32)(33)(34)(35). We identified a positive association between CTL4 c.-319C > T (rs5742909) and CRC susceptibility (dominant genetic model, p = 0.023).…”

Section: Discussionmentioning

confidence: 99%

Functional analysis of CTLA4 promoter variant and its possible implication in colorectal cancer immunotherapy

Angulo-Aguado,

Orjuela-Amarillo,

Mora-Jácome

et al. 2023

Front. Med.

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BackgroundColorectal cancer (CRC) is a prevalent cancer, ranking as the third most common. Recent advances in our understanding of the molecular causes of this disease have highlighted the crucial role of tumor immune evasion in its initiation and progression. CTLA4, a receptor that acts as a negative regulator of T cell responses, plays a pivotal role in this process, and genetic variations in CTLA4 have been linked to CRC susceptibility, prognosis, and response to therapy.MethodsWe conducted a case-control study involving 98 CRC patients and 424 controls. We genotyped the CTLA4 c.-319C > T variant (rs5742909) and performed an association analysis by comparing allele frequencies between the patients and controls. To assess the potential functional impact of this variant, we first performed an In Silico analysis of transcription factor binding sites using Genomatix. Finally, to validate our findings, we conducted a luciferase reporter gene assay using different cell lines and an electrophoretic mobility shift assay (EMSA).ResultsThe case-control association analysis revealed a significant association between CTLA4 c.-319C > T and CRC susceptibility (p = 0.023; OR 1.89; 95% CI = 1.11–3.23). Genomatix analysis identified LEF1 and TCF7 transcription factors as specific binders to CTLA4 c.-319C. The reporter gene assay demonstrated notable differences in luciferase activity between the c.-319 C and T alleles in COS-7, HCT116, and Jurkat cell lines. EMSA analysis showed differences in TCF7 interaction with the CTLA4 C and T alleles.ConclusionCTLA4 c.-319C > T is associated with CRC susceptibility. Based on our functional validation results, we proposed that CTLA4 c.-319C > T alters gene expression at the transcriptional level, triggering a stronger negative regulation of T-cells and immune tumoral evasion.

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The effect of CTLA-4 and CD28 gene variants and circulating protein levels in patients with gastric cancer

Cited by 8 publications

References 43 publications

Association Between the CD28 c.17 +3 T>C Polymorphism (rs3116496) and Cancer Risk: An Updated Meta-Analysis

Association Between the CD28 c.17 +3 T>C Polymorphism (rs3116496) and Cancer Risk: An Updated Meta-Analysis

Evidence of Association between CTLA-4 Gene Polymorphisms and Colorectal Cancers in Saudi Patients

Functional analysis of CTLA4 promoter variant and its possible implication in colorectal cancer immunotherapy

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