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Abstract Urothelial-bladder-carcinoma (UBC) 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 Objective: In this article, we indented firstly to scrutinise the influence of rs10889677”A/C” and rs-1884444 ”G/T” located in IL-23R-gene on UBC development and progression among Egyptians. The study further described how the these variants confers a contradictory influences on IL-23R-bearingimmune- cells, involving tumour-associated-macrophages (TAMs), naturalkillers(NKs) and CD4+ T-helper-cells and IL-23/IL-17 inflammatory axis.< Patients and Methods: The study was conducted on 100 UBC patients and 174 healthy controls. The genotyping analysis of these variants performed by RLFPPCR method. Based on immunophenotyping, the counts of cell-bearing receptor immune cells we detected. Eventually, we applied the ELISA-technique for determining the serum levels of IL-23R, IL23 and IL-17 .Results and Conclusion Findings revealed that the rs10889677”C”-allele was significantly correlated with increased serum levels of IL-23R concomitantly with increased UBC risk. Since its higher frequencies were plainly noticeable in high-grade and invasive-tumours (P<0.05) when applied the dominant homozygous and allelic genetic models (P<0.05). In contrast, the SNP rs- 1884444 ”G/T” was significantly associated with a reduced risk of UBC compared to controls observed under allelic and dominant models (P<0.05). Also, the frequency of the T-allele has dropped to very low values in the case of high-grades and invasive-tumors (P<0.05). Results also indicated that the levels of the receptor-bearing immune cells and the serum levels of IL23 and IL-17 could be altered in response to these variants but in a paradoxical manner (i.e anti-tumour profile in the rs-1884444 SNP case, but with a pro-tumour influence with respect to rs-10889677 and the latter variant contributes to creating inflammatory milieu more prone to bladder carcinogenesis. |