Alcoholic drinks are well known to have carcinogenic properties, and several possible mechanisms have been postulated to explain this. In general terms ethyl alcohol slows down protein synthesis. One obvious consequence of this is that cell repair mechanisms will be inhibited, which could lead to malignant changes. A synergy between alcohol and smoking is also well documented: heavy smokers who also drink heavily are many times more likely to develop oesophageal cancer than non-smokers who drink. In this case the harmful cellular effects of the chemicals and free radicals that are present in cigarette smoke are potentiated if the cells have already been damaged by chronic exposure to alcohol. But perhaps a more interesting question is why beer and spirits are strongly associated with upper digestive tract malignancies, whereas wine is apparently not. One hypothesis involves the action of nitrosamines. These are substances that are found in most alcoholic drinks and which become carcinogenic when metabolised. Among alcoholic drinks, beer usually contains the highest concentrations of nitrosamines (although the concentrations have declined in recent years as a result of changes in malting); distilled spirits also contain them, but at a lower concentration than beers. Typically, wines contain insignificant concentrations of nitrosamines. Animal studies have shown that the presence of ethyl alcohol blocks the metabolism of nitrosamine in the liver (usually mediated by cytochrome P-450). As a consequence, the nitrosamines are left intact and free to circulate to other organs, such as the kidneys and oesophagus, where they can be activated into carcinogens. A second line of research supports this theory. Scientists have looked at people who do not have cancer but who live in places with a high prevalence of oesophageal cancer associated with alcohol consumption—such as China and northern France. These people have been found to have a pattern of DNA damage in their oesophageal cells that is closely similar to that known to be caused by exposure to nitrosamines. In addition, the types and sites of mutation of the p53 gene (the tumour suppressor gene) that are commonly found within oesophageal cancer cells also reflect the pattern of DNA damage inflicted by nitrosamines. This confirms nitrosamine-like exposure in cases of oesophageal cancer and could explain why beer and spirits cause more cases of upper digestive tract malignancy than wine.