Association between CTLA-4 + 49A &gt; G and – 318C &gt; T single-nucleotide polymorphisms and susceptibility to thyroid neoplasm

Abtahi, Shabnam; Jahromi, Fatemeh Izadi; Dabbaghmanesh, Mohammad Hossein; Malekzadeh, Mahyar; Ghaderi, Abbas

doi:10.1007/s12020-018-1663-8

Cited by 6 publications

(2 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequent study showed that the substitution of C to T modified the consensus sequence that binds lymphoid enhancing factor 1 (LEF1) and further altered the activity of the CTLA4 promoter (Chistiakov, Savost'anov, Turakulov, Efremov, & Demurov, ). Thus, it is rational that rs5742909 SNP, which affects the expression of CTLA4, would contribute to development and treatment outcome of various immune‐related diseases including tumours, whereas rs5742909 SNP was not associated either the risk of lung cancer, thyroid carcinoma and nasal NK/T‐cell lymphoma or treatment outcome of lung cancer and multiple myeloma (Abtahi, Izadi Jahromi, Dabbaghmanesh, Malekzadeh, & Ghaderi, ; Cheng et al, ; Lee et al, ; Ma et al, ; Qin et al, ). Similarly, rs5742909 SNP had no effect on the risk of ESCC and survival of patients with ESCC in the population from Cixian high‐incidence region.…”

Section: Discussionmentioning

confidence: 99%

Association of cytotoxic T‐lymphocyte associated protein 4 gene polymorphisms with the risk and prognosis of oesophageal cancer in a high‐incidence region from northern China

Wang

et al. 2019

Int J Immunogenetics

View full text Add to dashboard Cite

The most important anti‐tumour immune response is mediated by T lymphocytes. Cytotoxic T lymphocyte‐associated protein 4 (CTLA4) plays a critical role in the immune surveillance against tumours as an inhibitory immune checkpoint molecule of T‐cell activation. This study was designed to explore the association of CTLA4 polymorphisms with the susceptibility to oesophageal squamous cell carcinoma (ESCC) and prognosis of patients with ESCC in a high‐incidence population from northern China. CTLA4 rs5742909 C/T and rs231775 G/A single nucleotide polymorphisms (SNPs) were genotyped using polymerase chain reaction–ligase detection reaction (PCR‐LDR) method in 577 ESCC patients and 580 controls. Upper gastrointestinal cancer family history increased the risk of ESCC (the sex‐, age‐ and smoking status‐adjusted OR = 1.383, 95%CI = 1.094–1.749). The genotype frequencies of these two SNPs in the patients with ESCC were similar to that in the controls. Survival analyses were conducted in 204 patients with ESCC with five‐year survival information. The mean survival time of ESCC patients with rs231775 SNP A/A genotype in age over 60 years group was 23.2 months, significantly shorter than that of those with G/G genotype (47.3 months). The A/A genotype was associated with increased death risk of patients with ESCC older than 60 years (adjusted HR = 4.544, 95%CI = 1.913–10.790). CTLA4 rs231775 SNP might be used as genetic marker of worse prognosis for patients with ESCC over 60 years in a high‐incidence population from northern China.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of cytotoxic T‐lymphocyte associated protein 4 gene polymorphisms with the risk and prognosis of oesophageal cancer in a high‐incidence region from northern China

Wang

et al. 2019

Int J Immunogenetics

View full text Add to dashboard Cite

show abstract

“…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.

View full text Add to dashboard Cite

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.

show abstract

Signal peptide missense variant in cancer-brake gene CTLA4 and breast cancer outcomes

Babteen

Fawzy

Alelwani

et al. 2020

Gene

View full text Add to dashboard Cite

Association between CTLA-4 + 49A > G and – 318C > T single-nucleotide polymorphisms and susceptibility to thyroid neoplasm

Cited by 6 publications

References 28 publications

Association of cytotoxic T‐lymphocyte associated protein 4 gene polymorphisms with the risk and prognosis of oesophageal cancer in a high‐incidence region from northern China

Association of cytotoxic T‐lymphocyte associated protein 4 gene polymorphisms with the risk and prognosis of oesophageal cancer in a high‐incidence region from northern China

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

Signal peptide missense variant in cancer-brake gene CTLA4 and breast cancer outcomes

Contact Info

Product

Resources

About