Sphingolipids and the link between alcohol and cancer.

Epidemiological evidence underscores alcohol consumption as a strong risk factor for multiple cancer types, with liver cancer being most commonly associated with alcohol intake. While mechanisms linking alcohol consumption to malignant tumor development are not fully understood, the likely players in ethanol-induced carcinogenesis are genotoxic stress caused by formation of acetaldehyde, increased oxidative stress, and altered nutrient metabolism, including the impairment of methyl transfer reactions. Alterations of sphingolipid metabolism and associated signaling pathways are another potential link between ethanol and cancer development. In particular, ceramides are involved in the regulation of cellular proliferation, differentiation, senescence, and apoptosis and are known to function as important regulators of malignant transformation as well as tumor progression. However, to date, the cross-talk between ceramides and alcohol in cancer disease is largely an open question and only limited data are available on this subject. Most studies linking ceramide to cancer considered liver steatosis as the underlying mechanism, which is not surprising taking into consideration that ceramide pathways are an integral part of the overall lipid metabolism. This review summarizes the latest studies pointing to ceramide as an important mediator of cancer-promoting effects of chronic alcohol consumption and underscores the necessity of understanding the role of sphingolipids and lipid signaling in response to alcohol in order to prevent and/or successfully manage diseases caused by alcohol.