The Evaluation of the Relationship between Bladder Cancer and Oxidative Stress Using NRF-2/KEAP-1Pathway, Zinc and Copper Levels

Purpose: It has been shown that Copper and Zinc contribute to the structure of the antioxidant enzymes. In addition, NRF-2 and KEAP-1 complex have a powerful effect on the intracellular organization of the antioxidants. We evaluated the relation of Copper, Zinc, NRF-2, and KEAP-1 complex regarding the oxidative stress with tumor stage - grade in patients with bladder cancer. Materials and Methods: A total of 52 patients (32 bladder cancer and 20 control group) were included in the study. The demographic properties of groups were identical. Serum NRF-2, KEAP-1, Cu, and Zn levels were compared by ELISA method between the groups, and tissue NRF-2, KEAP-1, Cu and Zn levels were evaluated also by ELISA method in cancer patients. Results: Serum levels of NRF-2 and KEAP-1 of the bladder cancer patients were found to be higher than the control group (p = 0.004 and p = 0.001, respectively). On the other hand serum levels of Copper and Zinc were found to be lower than the control group (p = 0.008 and p = 0.001, respectively). However, the subgroup analysis according to the stages and grades of the tumour showed no difference. The Copper level obtained from the tissue analysis was detected to be considerably decreased with tumour stage and grade. Conclusion: Bladder cancer patients had higher serum NRF-2 and KEAP-1 levels and lower serum Copper and Zinc levels. In addition, the Copper levels decreased with the tumour stage and grade. Studies with larger number of patients are needed to demonstrate the efficacy of these markers.