It has been recently shown that the transcriptional activation of TNF-α, IL-1β, and PTGS2 (COX-2) are among other early oncogenic molecular events that occur in the epithelium of the upper aerodigestive tract under its chronic exposure to known risk factors, such as tobacco smoke N-nitrosamines, with or without nicotine, and/or gastroesophageal refluxate, and can be prevented by the application of specific inhibitors [24,54,55,56,57]. The gene discussed is PTGS2; the disease is gastroesophageal reflux disease.