Molecular Basis for Maize as a Risk Factor for Esophageal Cancer in a South African Population via a Prostaglandin E2 Positive Feedback Mechanism

Abstract

The incidence of squamous cancer of the esophagus varies up to a hundredfold in different regions of the world. In Transkei, South Africa, a particularly high incidence of the disease is observed. We have previously proposed an association between a maize-rich diet and elevated levels of intragastric prostaglandin E2 production (PGE2). Here we investigate the molecular mechanisms by which a high-maize diet could lead to increased incidence of squamous cancer of the esophagus. We confirm that levels of PGE2 are high (606.8 pg/ml) in the gastric fluid of individuals from Transkei. We also show that treatment of esophageal cells with linoleic acid, which is found at high levels in maize and is a precursor to PGE2, leads to increased cell proliferation. Similarly, treatment of cells with PGE2 or with gastric fluid from Transkeians also leads to increased proliferation. Our data suggest that the high levels of PGE2 associated with a maize-rich diet stimulate cell division and induce the enzyme COX 2, resulting in a positive feedback mechanism that predisposes the esophagus to carcinoma.