In conclusion, we hypothesize that the oriental ALDH2*504Lys variant might have originated in the ancient Han Chinese population in Central China and spread to most areas of East Asia with the expansion of Han Chinese and their genetic influences on neighboring populations over the past few thousand years. Some diseases such as esophageal cancer show a complex relationship with the frequency of ALDH2*504Lys. Where the ALDH2*504Lys frequency is high for whatever reason, as in Southeast China, there is a clear increased risk of esophageal cancer in heterozygotes that results in higher esophageal cancer incidences in some subregions. In other areas of China there is also an increased risk of esophageal cancer in heterozygotes (Yang et al., 2007; Wu et al., 2001; Chen, 2005; Yang, 2005; Xiao, 2007) but the lower frequency of ALDH2*504Lys is not sufficient to explain the high incidence of esophageal cancer. More genetic epidemiological investigations in China are required to reveal any possible reciprocal relationship between esophageal cancer and the ALDH2*504Lys allele and identify the other risk factors that appear to be present.
