A narrative review on alcohol and alimentary tract cancer with special emphasis on acetaldehyde and oxidative stress

Abstract

Approximately 4% of all cancer cases worldwide are caused by alcohol consumption (oropharynx, larynx, esophagus, stomach, colorectum, liver and the female breast). Various mechanisms contribute to ethanol-mediated carcinogenesis, including the action of acetaldehyde, the first metabolite of ethanol oxidation and oxidative stress primarily promoted through the induction of cytochrome P4502E1. Acetaldehyde is toxic and carcinogenic, binds to DNA and proteins, inhibits the oxidative defense- and the nuclear repair system, and prevents DNA methylation. High levels of acetaldehyde occur through increased production in the presence of a hyperactive alcohol dehydrogenase (ADH1C*1,1) or decreased degradation in the presence of low active aldehyde dehydrogenase (ALDH2*1,2). In addition, microbes of the upper alimentary tract and the colorectum effectively produce acetaldehyde from ethanol. In addition, ethanol induces cytochrome P4502E1 resulting in an enhanced ethanol metabolism and the generation of reactive oxygen species (ROS). ROS may cause lipid peroxidation (LPO) with the LPO-products 4-hydroxynonenal or malondialdehyde, which may form highly carcinogenic etheno DNA-adducts CYP2E1 is also involved in the activation of a variety of dietary and tobacco procarcinogens and in the degradation of retinoic acid. Alcohol also influences tumor promotion, such as epigenetics with a change in DNA methylation and histone modification, and affects a variety of cancer genes and signaling pathways. Preventive measures include reducing alcohol consumption, quitting smoking and keeping good oral hygiene. Alcohol consumers – especially when they smoke or belong to genetic risk groups – should be regularly checked for cancer of the upper alimentary tract, for alcohol- associated liver disease, and for breast cancer. Cessation or reduction of alcohol consumption definitively reduces cancer risk.

Zusammenfassung

Ungefähr 4% aller Krebsfälle weltweit werden durch Alkohol verursacht (Mundhöhle, Pharynx, Larynx, Ösophagus, Magen, Kolorektum, Leber und weibliche Brustdrüse). Verschiedene Mechanismen wie Azetaldehyd, das erste Stoffwechselprodukt von Äthanol und oxidativem Stress, primär hervorgerufen durch die Induktion von Zytochrom P4502E1 (CYP2E1), tragen hierzu bei. Azetaldehyd ist toxisch und karzinogen, bindet an Proteine und DNA, hemmt das anti-oxidative Abwehr- und nukleäre DNA-Reparationssystem, und verhindert die DNA-Methylierung. Hohe Azetaldehydspiegel entstehen durch erhöhte Produktion in der Gegenwart der hyperaktiven Alkohol-dehydrogenase (ADH1C*1,1) oder durch einen verminderten Abbau in der Gegenwart der niedrig aktiven Azetaldehyd-dehydrogenase (ALDH2*1,2). Zusätzlich produzieren Bakterien des oberen Verdauungstraktes und des Kolorektums Azetaldehyd aus Äthanol. Das durch Äthanol induzierte CYP2E1 ist für einen gesteigerten Äthanolstoffwechsel und für die Generierung von reaktiven Sauerstoff-Species (ROS) verantwortlich. ROS kann zur Lipid Peroxidation (LPO) mit den LPO-Produkten 4-Hydoxynonenal und Malondialdehyd führen, die ihrerseits zur Bildung hochkarzinogener etheno DNA-Addukte beitragen. CYP2E1 ist auch bei Aktivierung verschiedener Karzinogene in Nahrungsmittel und Tabak, sowie beim Abbau von Retinsäure beteiligt. Alkohol ist zudem ein Tumorpromotor. Alkohol verursacht epigenetische Veränderungen bei der Methylierung von DNA und bei der Histon-Modifikation, und beeinflusst verschiedene Gene und Signalwege, die bei der Krebsentstehung von Bedeutung sind. Vorsorge und Früherkennung beinhalten Alkoholreduktion, Aufhören zu rauchen, sowie eine sorgfältige Mundhygiene. Alkoholkonsumenten, besonders, wenn sie rauchen oder zu einer genetischen Risikogruppe gehören, sollten regelmäßig auf Karzinome des oberen Verdauungstraktes, auf eine alkoholbedingte Lebererkrankung und auf Brustkrebs untersucht werden. Alkoholabstinenz oder Alkoholreduktion reduzieren definitiv das Krebsrisiko.

Keywords

ethanol - acetaldehyde - oropharynx cancer - hepatocellular cancer - colorectal cancer - cytochrome P4502E1

Schlüsselwörter

Äthanol - Azetaldehyd - Oropharynxkarzinom - hepatozelluläres Karzinom - kolorektales Karzinom - Cytochrom P5402E1

Publikationsverlauf

Eingereicht: 23. Januar 2025

Angenommen nach Revision: 17. April 2025

Artikel online veröffentlicht:
16. Mai 2025

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