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Biological Basis of Alcohol-Induced Cancer pp 265–279Cite as

Genetic Polymorphisms of Alcohol Dehydrogense-1B and Aldehyde Dehydrogenase-2, Alcohol Flushing, Mean Corpuscular Volume, and Aerodigestive Tract Neoplasia in Japanese Drinkers

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 815))

Abstract

Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1 %) and head and neck SCC (1.0 %). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (≈ 180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0 % of 4,879 alcoholics had a history of (4.0 %) or newly diagnosed (1.0 %) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7 % of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5 % of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV ≥ 106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia.

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Author information

Authors and Affiliations

  1. National Hospital Organization Kurihama Medical and Addiction Center, 5-3-1 Nobi, Yokosuka, Kanagawa, 239-0841, Japan

    Akira Yokoyama M.D. & Takeshi Mizukami M.D.

  2. Department of Health Promotion, National Institute of Public Health, Saitama, Japan

    Tetsuji Yokoyama M.D.

Authors
  1. Akira Yokoyama M.D.
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  2. Takeshi Mizukami M.D.
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  3. Tetsuji Yokoyama M.D.
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Corresponding author

Correspondence to Akira Yokoyama M.D. .

Editor information

Editors and Affiliations

  1. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA

    Vasilis Vasiliou

  2. Distilled Spirits Council of the United States, Washington, District of Columbia, USA

    Samir Zakhari

  3. Centre of Alcohol Research, University of Heidelberg, Germany and Salem Medical Centre, Heidelberg, Germany

    Helmut K. Seitz

  4. Department of Pathology, Anatomy, & Cell, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Jan B. Hoek

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Yokoyama, A., Mizukami, T., Yokoyama, T. (2015). Genetic Polymorphisms of Alcohol Dehydrogense-1B and Aldehyde Dehydrogenase-2, Alcohol Flushing, Mean Corpuscular Volume, and Aerodigestive Tract Neoplasia in Japanese Drinkers. In: Vasiliou, V., Zakhari, S., Seitz, H., Hoek, J. (eds) Biological Basis of Alcohol-Induced Cancer. Advances in Experimental Medicine and Biology, vol 815. Springer, Cham. https://doi.org/10.1007/978-3-319-09614-8_15

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