No abstract

Although cancer mortality has declined among the general population, the incidence of melanoma continues to rise. While identifying high-risk cohorts with genetic risk factors improves public health initiatives and clinical care management, recognizing modifiable risk factors such as social-environmental risk factors would also affect the methods of patient outreach and education. One major modifiable social-environmental risk factor associated with melanoma is ultraviolet (UV) radiation. However, not all forms of melanoma are correlated with sun exposure or occur in sun-exposed areas. Additionally, UV exposure is rarely associated with tumor progression. Another social-environmental factor, pregnancy, does not explain the sharply increased incidence of melanoma. Recent studies have demonstrated that alcohol consumption is positively linked with an increased risk of cancers, including melanoma. This perspective review paper summarizes epidemiological data correlating melanoma incidence with alcohol consumption, describes the biochemical mechanisms of ethanol metabolism, and discusses how ethanol and ethanol metabolites contribute to human cancer, including melanoma.

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.

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