The exact timing at which NRF2 activity is elevated in oesophageal carcinogenesis has not been determined but analysis of in situ ESCC tumours revealed the absence of NFE2L2 mutation, suggesting that these mutations may not be associated with the initial stages of ESCC cancer but may occur later to influence cancer progression [239]. Here, NFE2L2 is linked to esophageal squamous cell carcinoma.