NFE2L2 and Familial prostate cancer: However, despite indications of Nrf2 overexpression in malignant cells22,25, several authors demonstrated evidences that cytoprotective enzymes are downregulated in prostate cancer, partially due to hypermethylation of CpG sites in the Nrf2 gene21,26,27; thus, the role of Nrf2 on the susceptibility of prostate cancer to oxidative stress remains controversial.