This model could be translated into esophageal pathophysiology: the gastro-esophageal reflux will lead to a chronic inflammatory insult to the esophageal mucosa with a concurrent SCCA-1 up-regulation and disruption of the esophageal mucosa barrier to external stimuli, with an accelerated process of mucosa metaplastic transformation. The gene discussed is SERPINB4; the disease is gastroesophageal reflux disease.