Ethanol Metabolism and Melanoma

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Abstract
Malignant melanoma is the deadliest form of skin cancer. Despite significant efforts in sun protection education, melanoma incidence is still rising globally, drawing attention to other socioenvironmental risk factors for melanoma. Ethanol and acetaldehyde (AcAH) are ubiquitous in our diets, medicines, alcoholic beverages, and the environment. In the liver, ethanol is primarily oxidized to AcAH, a toxic intermediate capable of inducing tumors by forming adducts with proteins and DNA. Once in the blood, ethanol and AcAH can reach the skin. Although, like the liver, the skin has metabolic mechanisms to detoxify ethanol and AcAH, the risk of ethanol/AcAH-associated skin diseases increases when the metabolic enzymes become dysfunctional in the skin. This review highlights the evidence linking cutaneous ethanol metabolism and melanoma. We summarize various sources of skin ethanol and AcAH and describe how the reduced activity of each alcohol metabolizing enzyme affects the sensitivity threshold to ethanol/AcAH toxicity. Data from the Gene Expression Omnibus database also show that three ethanol metabolizing enzymes (alcohol dehydrogenase 1B, P450 2E1, and catalase) and an AcAH metabolizing enzyme (aldehyde dehydrogenase 2) are significantly reduced in melanoma tissues.
Funding Information
  • National Institutes of Health (NIH)/National Cancer Institute (NCI) (R01CA197919, R01AI156534-01A1, 5I01BX001228, R21AA028904)
  • National Institute of Allergy and Infectious Diseases (R01CA197919, R01AI156534-01A1, 5I01BX001228, R21AA028904)
  • Veterans Affairs Merit Review Award (R01CA197919, R01AI156534-01A1, 5I01BX001228, R21AA028904)
  • NIH/National Institute on Alcohol Abuse and Alcoholism (NIAAA) (R01CA197919, R01AI156534-01A1, 5I01BX001228, R21AA028904)
  • Cancer League of Colorado (R01CA197919, R01AI156534-01A1, 5I01BX001228, R21AA028904)
  • Dermatology Foundation (R01CA197919, R01AI156534-01A1, 5I01BX001228, R21AA028904)
  • University of Colorado Cancer Center-Nutrition Obesity Research Center (UCCC-NORC) Metabolism and Cancer Pilot Grant (R01CA197919, R01AI156534-01A1, 5I01BX001228, R21AA028904)
  • Melanoma Research Alliance (R01CA197919, R01AI156534-01A1, 5I01BX001228, R21AA028904)

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