Nitric oxide in the molecular pathogenesis of esophageal (barrett) adenocarcinoma

Esophageal cancer is a global health problem. Over the past three decades there has been a dramatic increase in the incidence of esophageal adenocarcinoma. This cancer has a dismal prognosis, and it therefore seems likely that significant progress in prevention, palliation or cure will only be made with an improved understanding of its causes and tumor biology. Our recent identification of molecular alterations associated with the premalignant stage of this disease (Barrett esophagus), suggesting a link between chronic inflammation and malignant progression, offers a particularly attractive approach to this problem, and this study represents a unique research approach to improve our understanding of critical early genetic events in esophageal malignancy. This proposed study has direct relevance to an estimated 1,300 Canadians who will be diagnosed with esophageal cancer this year. It will also be of interest to an estimated 5 million Canadians who experience chronic gastroesophageal reflux, and who may be at risk for Barrett esophagus due to genetic susceptibility, lifestyle or environment.