Epidemiological studies have shown several strong predictors for selecting Japanese persons at high risk for esophageal squamous cell carcinoma (ESCC). (1) Alcohol consumption and tobacco smoking synergistically increase the risk, and a low intake of green and yellow vegetables or fruit and a low body mass index also increase the risk of ESCC. (2) The presence of esophageal distinct iodine-unstained lesions and melanosis are associated with an increased risk of ESCC. (3) The combination of alcohol consumption and inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) and less-active homozygous alcohol dehydrogenase-1B (ADH1B) increases the risk of ESCC in a multiplicative fashion. (4) The results of a simple flushing questionnaire predict the ALDH2 phenotype with a high accuracy. (5) High mean corpuscular volume (MCV), which is induced by heavy drinking, high acetaldehyde exposure, heavy smoking, and poor nutrition, may be useful in identifying high-risk persons. Endoscopic screening with esophageal iodine staining in Japanese high-risk populations yields very high rates of early ESCC. Treatment of early ESCC by endoscopic mucosectomy has become a widespread practice in Japan and has succeeded in improving the outcome of this high-mortality cancer. New evidence concerning ALDH2/ADH1B/alcohol flushing/MCV-related cancer susceptibility has renewed interest in alcohol and acetaldehyde as important subjects for cancer research and has served as a powerful tool for cancer prevention and cancer screening of Japanese subjects.
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