Rs-10889677 variant in interleukin-23 receptor may contribute to creating an inflammatory milieu more susceptible to bladder tumourigenesis: report and meta-analysis

AbstractBladder cancer (BLC) is a recurrent high-risk malignancy typified by an inherent localised chronic inflammation. IL-23-receptor (IL-23R), as a positive regulator in the priming of T helper-17 cells, is regarded a principal coordinator of inflammation-propelled neoplasia. In this article, we indented firstly to scrutinise the influence of rs10889677 “A/C” SNP located in IL-23R-gene on BLC development and progression among Egyptians. Findings revealed that the rs10889677“C” allele was significantly associated with the increased BLC risk and its higher frequencies were plainly noticeable in high-grade and invasive tumours when applied the dominant/homozygous/allelic genetic models. Under the same genetic models, elevated serum levels of IL-23R protein in BLC patients were pertinently correlated with the rs10889677“A/C” polymorphism. As a corollary, the frequent up-regulation of IL-23R exerts a subsequent activation of the IL-23/ 17 inflammatory axis. That is experienced as a drastic increase in IL-23 and IL17 levels under the dominant/homozygous/heterozygous/recessive models. Second, study further described how the rs10889677 variant confers its pro-tumoural influences on IL-23R-bearing immune cells, involving tumour-associ ated macrophages (TAMs), natural killers (NKs) and CD4+ T-helper cells. When the dominant model was adopted, it was observed that patients bearing the rs10889677 “C” allele had lower counts of IL-23R-positive CD56+NKs and CD4+ T-cells,...
Source: Immunogenetics - Category: Genetics & Stem Cells Source Type: research