Molecular basis for maize as a risk factor for oesophageal cancer in a South African population

Throughout the world squamous cell carcinoma of the oesophagus seems to be an increasing problem. There is a huge variation in prevalence globally; locations such as Japan, Iran, China and Finland can have ten times the prevalence compared to other western countries. One place that is hugely affected is Transkei, a 16,000 square mile area of South Africa. Some of the factors proposed to be implicated with squamous cell carcinoma in this region include tobacco smoking, alcohol consumption, bacterial infections and fungal infection of common food crops. In addition, the ‘Sammon theory’ links carcinogenesis in Transkei to the high consumption of maize by the population. Through a chain of reactions it is postulated that a component of maize inhibits the breakdown of growth factors, which have already been implicated in cancer. This study investigates the Transkei population and updates the Sammon theory with current research to predict a theory at a molecular level. This theory is then tested with novel research to show PGE2, shown here in high concentrations in gastric fluid samples, directly increases the proliferation of oesophageal cell lines. Gastric fluid samples from the Transkei population are then shown to have a mitogenic effect on oesophageal cells, supporting a theory that gastric fluid regurgitation commonly found in this population predisposes them to cancer. Further experimentation on the expression of related proteins shows how high PGE2 may increase its own production by increasing COX 2 expression, leading to a positive feedback loop causing constant proliferative stimulation of the oesophageal squamous tissue in the presence of the COX 2 substrate, aracadonic acid. Therefore this thesis suggests that a high maize diet provides the correct conditions for regurgitation of increased concentrations of PGE2 into the oesophagus leading to squamous hyper-proliferation over long periods of time through self stimulated production, which would normally have ceased over a much shorter time if only localised PGE2 was produced through natural restitution.