Aetiology of cancer of the oesophagus: geographical studies in the footsteps of Marco Polo and beyond.

Three areas in the world have a high prevalence of cancer of the oesophagus. Two lie at the extremes of the old silk routes pioneered by Marco Polo around the shores of the Caspian Sea in northern Iran and in the Henan and Shanxi provinces of China. The third area, with the highest prevalence, is the Homeland state of Transkei in South Africa. Cancer of the oesophagus here is 14 times more common than hepatoma the next most common malignant tumour and in southern districts accounts for 20% of all adult deaths. ' Possible aetiological factors include a similar diet; in particular, a diet rich in cereal but poor in fresh fruit and vegetables. In the Chinese regions a pot of millet gruel is often the sole food while home-made bread is the staple diet around the Caspian littoral. In Transkei, maize is grown to the virtual exclusion of all else irrespective of the suitability of the soil or climate. These diets are deficient in riboflavin and vitamins A and C. The three areas also share similar poor quality soil, deficient in trace elements, especially zinc and molybdenum. Zinc deficiency has been implicated in the development of oesophageal cancer under experimental conditions2 whilst molybdenum is a cofactor for the enzyme nitrate reductase so that deficiency allows nitrosamines to accumulate in plants. Each of the three areas have regional peculiarities which are probably of aetiological significance. Alcohol and tobacco, major risk factors in the West, play little or no role in Islamic Iran. The use of opium, however, correlates closely with local variations in oesophageal cancer incidence. Tests for urinary morphine metabolites indicate that the majority of the adult population are opium addicts in affected areas. The tarry residues from opium pipes are frequently eaten mimicking similar practices seen in the Transkei.3 The disease in China is particularly common around the foothills of the Taihung mountain range in the north east. The ancients recognised the sinister portent of dysphagia where a 'Throat-God Temple' existed which sadly was destroyed by war in 1927. Nitrosamines and their precursors have been identified in drinking water and food samples.4 In Linxian, for example dry wells are used to collect and store rain water. This water is contaminated with human and animal waste but even so is taken home for storage in large ceramic jars. The nitrite content is considerably higher than the levels found in well water in areas of low incidence. Food is often contaminated with fungi and several species can reduce nitrates to nitrites. Both mouldy food