Sequence Variants in PSMB8/PSMB9 Immunoproteasome Genes and Risk of Urothelial Bladder Carcinoma.

BACKGROUND

The  and immunoproteasomegenes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. Because recent evidence has demonstrated an immunological role for proteasomes in various malignancies, including urothelial bladder carcinoma (UBC), we evaluated single nucleotide polymorphisms (SNPs) in  and . We determined any associations between these SNPs and susceptibility to UBC in the Saudi community.

METHODS

Samples of genomic DNA were taken from buccal cells of 111 patients with UBC and 78 healthy controls. TaqMan Real-Time PCR was used to determine genotype distributions and allele frequencies for the  rs17587 G>A and  rs2071543 G>T SNPs. We used SNPStats (https://www.snpstats.net) to choose each SNP's best interactive inheritance model.

RESULTS

The  rs17587 SNP was associated with the risk of UBC (odds ratio [OR] = 5.21,  < 0.0001). In contrast, the  rs2071543 SNP showed no association with UBC risk (OR = 1.13,  = 0.7871). In terms of genotypic distribution, the rs17587 G>A SNP was more frequent in UBC cases than controls in both the dominant (OR = 7.5; 95% confidence interval, 3.7-15.1;  = 0.0051) and recessive (OR = 17.11, 95% confidence interval 5.1-57.4;  = 0.0026) models. Genotypic distribution of the  rs2071543 G>T SNP was not significantly different between cases and controls in any interactive inheritance models ( > 0.05).

CONCLUSION

These results suggest a potential role for  as a biomarker for increased UBC risk. Discovering more genetic variants within immunoproteasome genes related to antigen presentation could help further our understanding of this risk.