The rs3757385 polymorphism increases IRF5 expression and systemic nitric oxide metabolites, protecting urothelial bladder cancer patients from recurrence.

BACKGROUND

Urothelial bladder cancer (UBC) is the ninth most common cancer worldwide. It is essential to investigate factors that may affect susceptibility and determine the prognosis of UBC. IRF5 is an interferon regulatory factor that modulates cellular differentiation during immune responses and oncogenesis.

METHODS AND RESULTS

The frequency of the rs3757385 (T > G) variant in IRF5 was evaluated in 295 patients with UBC and 295 individuals without neoplasia in a Brazilian population. Nitric oxide metabolites (NOx) systemic levels and IRF5 expression in normal and tumoral bladder tissues were also evaluated, as was the interaction between these parameters and prognostic indicators. Bioinformatics analyses compared gene expression patterns with TCGA data. The polymorphism was not associated with susceptibility to UBC. The mutated allele (G) was associated with a decrease in the relapses in the genotypic (OR = 0.205) and dominant (OR = 0.380) models. Hypertensive individuals with TG (genotypic, OR = 0.079) or TG + GG (dominant model, OR = 0.184) had fewer muscle-invasive tumors. Polymorphism did not alter the plasmatic NOx levels. Higher IRF5 expression was observed in patients with at least one G allele, males, smokers, and alcoholics. Directly, NOx was not associated with the prognostic parameters; however, individuals with the G allele and high NOx levels showed protection against relapses.

CONCLUSION

Our study highlights the association between rs3757385 (G allele) and high plasmatic NOx levels as good prognostic factors in UBC.