Objective: Owing to the putative role of Nrf2 in the activation of anti-oxidative genes, the present study aims at investigating the role of Nrf2 expression and its mutated form in breast cancer patients with no previous therapy.

Patients and Methods: In the case-control study, breast cancer patients and controls from the Western Kurdish population of Iran were selected to evaluate the genotype of Nrf2 (rs6721961) by PCR- restriction fragment length polymorphism. In addition, the statistical association between Nrf2 (rs6721961) mutation and the expression of Nrf2, ER, PR, Her2, SOD, catalase, and other clinicopathological characteristics were analyzed.

Results: The mean age of patients and controls were 43.55±1.89 and 46.44±2.16, respectively. In the control group, Nrf2 rs6721961 mutation deviated from Hardy-Weinberg Equation (HWE) with a p-value of 0.035 while in the patients’ group, SNP exact test for HWE showed a satisfied association with HWE (p=0.7). Besides, there was no significant relation between Nrf2 expression and catalase activity (p= 0.28) while SOD activity had a meaningful association with Nrf2 expression (p=0.02). There was no meaningful association of SNP with the expression levels of Her2 (p=0.30), ER (p=0.60) and PR (p=0.63). Besides, SNPSTAT showed that the expressions of Her2, ER and PR were in agreement with HWE.

Conclusions: The results indicated that Nrf2 mutation is an imperative effector in the risk of breast cancer. Besides, the interplay of Nrf2 with other main biomarkers of oxidative stress seems to pave the way towards novel and convenient treatment options.