Turning to the ADH7 variant, the product of the ADH7 gene is ADH4, formerly known as class IV or σ ADH. ADH4 is most highly expressed in the stomach, but is also expressed in cells of the UADT [12,13]. The physiological role for ADH4 is most likely as a retinol dehydrogenase, but this enzyme also has a high capacity for ethanol oxidation [14]. While the Km of human ADH4 for ethanol (28 mM) is quite high compared with that of ADH1B (4 mM), [15] the concentration of ethanol in many alcoholic beverages is in the molar range. Also, under laboratory conditions, salivary ethanol levels during alcohol drinking are 35-50 mM, depending on the type of beverage [16]. Therefore, it is likely that ADH4 could function as an alcohol dehydrogenase in the human UADT during alcohol drinking. If so, ethanol could act as an inhibitor of retinol metabolism by ADH4, thereby interfering with the retinoid-dependent differentiation of oesophageal cells, which could contribute to alcohol-related carcinogenesis [17].
