GLRX2 polymorphism and oxidative stress levels impact urothelial bladder cancer outcomes

The bladder is continuously exposed to oxidative and mutagenic agents. Such chemicals are metabolized, filtered by the kidneys, and excreted in the urine. Not surprisingly, urothelial bladder cancer (UBC) is the 9th most common cancer worldwide. This study investigates whether the C > T (rs912071) polymorphism in the Glutaredoxin 2 (GLRX2) gene, oxidative stress marker levels, and GLRX2 expression are associated with prognosis and recurrence in 341 patients with UBC. Gene expression data were compared to those available in TCGA. The TT genotype (OR = 2.475, p = 0.017) was positively associated with the risk of 1-year recurrence. Hypertensive patients carrying the CT genotype presented a reduced risk for recurrence (OR = 0.460, p = 0.047) and high-grade tumors (OR = 0.188, p = 0.001). Lipid peroxidation and nitric oxide metabolites (NOx) levels were higher in patients than in controls and in patients carrying the TT genotype. Tumor tissues and invasive tumors had higher GLRX2 expression, confirming the TCGA findings. DepMap analysis identifies GLRX2 as a valuable tool enabling personalized treatments for UBC patients. Our results showed that the TT genotype of rs912071 is associated with an increased risk of recurrence and high oxidative stress. In contrast, the CT genotype may protect against disease recurrence in patients with UBC cancer.