Direct exposure to acid and bile reflux and the subsequent chronic inflammation are two potential sources of oxidative damage characteristic of patients with BE [37]–[39].The higher frequency of p16 mutation at later stages of BE and the fact that genetic alterations that have been shown to occur later during neoplastic progression in BE, such as p53 mutations, also display a similar mutation spectrum [36], suggest that the ROS generated by tissue damage and inflammation continue to act through neoplastic progression. The gene discussed is TP53; the disease is bile reflux.