Whatever positive selection may have increased the frequency of ALDH2*504Lys, serious diseases such as esophageal cancer or ischemia could act to decrease the ALDH2*504Lys allele frequency among the populations since studies report that heavy alcohol drinkers who are heterozygotes for ALDH2*504Lys have higher risk for esophageal cancer (Yokoyama & Omori, 2005; Yang et al., 2007; Li et al., 2008). In addition, ALDH2 activation was shown to reduce ischemic damage to the heart, suggesting that patients with reduced ALDH2 activity may suffer increased damage during cardiac ischemic events or coronary bypass surgery (Chen et al., 2008). The typical age of onset for esophageal cancer in the high incidence area can be earlier than 30 (He et al., 2006). We compared the geographic distribution of esophageal cancer incidence with the ALDH2*504Lys allele and carrier frequency distributions. We collected the male esophageal cancer incidence data of 355 populations from the literature, covering most countries in the world (Table S2). Central and Southeast China were examined in detail. Figure 3 illustrates the world distribution of esophageal cancer incidence and the details in East Asia.
