Risk appraisal and endoscopic screening for esophageal squamous cell carcinoma in Japanese populations

Abstract

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 fl ushing 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 fl ushing/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.

Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: molecular mechanisms of carcinogenesis

“…AD is a carcinogen in various animals, because AD may induce gene mutations [3,12]. Epidemiological studies clearly demonstrate that the inactive ALDH2 encoded by the ALDH2*1/2*2 genotype, which causes an increased accumulation of AD following alcohol consumption, is a strong risk factor for the development of UADT cancers, in particular esophageal cancer [13,14]. This fact indicates the carcinogenicity of AD.…”

“…Moreover, because further metabolism of AD to acetate by oral bacteria is limited, the AD concentration in the saliva can be 10-100 times higher than that in the blood [15]. It is possible that AD is involved in UADT carcinogenesis, including carcinogenesis in the esophagus, because AD in saliva comes into direct contact with the mucosa of the UADT [3,14].…”

“…There are unique mechanisms of topical AD production from local ethanol in the UADT [14]. Increasing alcohol consumption results in increasing AD concentration in the saliva which is higher than that in blood.…”

Oesophageal squamous cell carcinoma (ESCC): Advances through omics technologies, towards ESCC salivaomics

“…Besides, an additional problem for ESCC is the multifactorial nature of its occurrence (20), and the influence that different habits would have over the risk of developing this disease, as it has been associated with heavy smoking, drinking, or low intake of vegetables or fruits (21)(22)(23). The increased risk factor in this case as indicated by Cheng and Day (22) may come as a consequence from a direct contact of the potential carcinogen with the epithelium, some existing transport facilitating mechanism, or derived from compounds that increase the cell turnover in the epithelial cells.…”