Rs-1884444 G/T variant in IL-23 receptor is likely to modify risk of bladder urothelial carcinoma by regulating IL-23/IL-17 inflammatory pathway.
Cytokine
; 138: 155355, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33187815
ABSTRACT
Bladder urothelial carcinoma (BUC) is a chronic relapsing urological malignancy, which poses a serious threat to human life. Non-resolving chronic-inflammation at the neoplastic site is associated consistently with inducing tumor-progression and poor patient outcomes. Interleukin 23 receptor (IL-23R) is a key element in T-helper 17 cell-mediated inflammatory process, that plays a critical role in orchestrating tumor-promoting inflammation. Therefore, we hypothesized that potentially functional genetic variant rs1884444 G/T of IL-23R may modify BUC risk. To validate this hypothesis, our findings demonstrated that the rs1884444 G/T variant was significantly associated with a reduced risk of BUC compared to controls observed under allelic (T vs. G) and dominant (GT + TT vs. GG) models (P < 0.05). In addition, the frequency of the T-allele has dropped to very low values in the case of high-grades and invasive-tumors (P < 0.05). Thus, T-allele has emerged as a reliable genetic marker for good prognosis of BUC. In tumorgenesis, the binding-affinity of the receptor seemed to be distorted by the effect of the non-conservative G/T variation, which in turn caused the IL-23/IL-17 pathway to be disabled. This was recognized by low levels of IL-23 and IL-17 in the serum of patients, under the influence of all the tested genetic models (P < 0.01). Results also indicated that the level of the receptor-bearing immune cells could be altered in response to the G/T protective effect. For example, the median counts of T-helper CD4+ cells and CD56+ natural killers increased significantly in conjunction with the decrease in the median count of CD14+ tumor-associated-macrophages under the dominant model. Nevertheless, the causative link between this subtle polymorphism and the immune-surveillance against BUC needs further in-depth investigation. Overall, we concluded that the rs-1884444 G/T variant is highly-associated with a reduction in the BUC risk, which may occur via deregulation of the IL-23/IL-17 pathway.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
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Carcinoma
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Receptores de Interleucina
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Urotélio
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Interleucina-17
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Polimorfismo de Nucleotídeo Único
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Subunidade p19 da Interleucina-23
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
/
Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cytokine
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Egito