For example, a Japanese large-scale population-based cohort study showed that heavy alcohol consumption and cigarette smoking are strongly associated with ESCC, especially among heavy smokers with inactive allele of ALDH2, the so-called flushing response to alcohol [24], while smokers after an ethanol challenge had 7 times higher salivary acetaldehyde levels than non-smokers [27,28]. The gene discussed is ALDH2; the disease is esophageal squamous cell carcinoma.