NFE2L2 and familial pancreatic carcinoma: Increased Nrf2 activity in CRC may occur for a number of reasons: hypermethylation of the Keap1 promoter region is common in CRC cell lines, suppressing its mRNA expression [27]; somatic mutations in Keap1 were found in 8% of CRCs, resulting in loss of inhibitory function [21]; and activation of the KRAS-MEK-ERK pathway has been associated with high levels of Nrf2 expression in lung and pancreatic cancer [17, 28].