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

Bladder 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 rs10889677A/C SNP located in IL-23R-gene on BLC development and progression among Egyptians. Findings revealed that the rs10889677C 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 rs10889677A/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-associated 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, in tandem with higher levels of IL-23R-positive CD14(+) TAMs compared with those with rs10889677 A allele. To entrench the idea, we did a meta-analysis on BLC patients from three different ethnicities (Asian, Caucasians and African). We observed that rs10889677SNP is significantly correlated with increased risk of BLCs in the overall population using over-dominant model. Consequently, authors suggested that the rs10889677 variant could be directly implicated in developing inflammatory environment more prone to generating malignancy.

Automated summary

The study examined the impact of the rs10889677A/C SNP in the IL-23R gene on the development and progression of bladder cancer in Egyptians, finding a significant association of the rs10889677C allele with increased risk of BLC. Additionally, elevated serum levels of IL-23R protein in BLC patients were correlated with the rs10889677A/C polymorphism. Meta-analysis across different ethnicities confirmed the SNP's significant correlation with increased risk of bladder cancer in the overall population.