Chronic alcohol consumption is a risk factor for tumours of the oral cavity, pharynx, larynx, oesophagus, liver, colorectum and the female breast. Various mechanisms contribute to alcohol-mediated carcinogenesis, including the action of cytochrome P-4502E1 (CYP2E1). CYP2E1 is one of 57 cytochrome P450 enzymes that are responsible for over 90% of the redox reactions of chemicals, including drugs, vitamins, steroids, chemical carcinogens, and industrial compounds. CYP2E1 is an important constituent of microsomal ethanol oxidation and is significantly induced by chronic ethanol consumption, which results in an increase of ethanol oxidation. CYP2E1 is present in almost all tissues, but predominantly in the liver. The increase of CYP2E1 following chronic ethanol consumption results in an enhanced activation of a variety of environmental procarcinogens present in food and especially tobacco smoke. CYP2E1 is also responsible for the degradation of retinol and retinoic acid (RA), which is associated with changes in cell differentiation, cell proliferation and apoptosis, leading to a precancerous cell cycle behaviour. Subsequently, CYP2E1 generates reactive oxygen species (ROS), which either bind directly to DNA or which result in lipid peroxidation (LPO) with LPO products such as 4-hydroxy-nonenal and malondialdehyde. These compounds can bind to DNA and may form highly carcinogenic etheno DNA-adducts. Thus, the induction of CYP2E1 by chronic alcohol ingestion is an important factor to trigger ethanol-mediated carcinogenesis.
- Nutr Cur 2024; 03(Special 1): e150
Alcohol use disorder (AUD) is frequent globally and is responsible for more than 5% of the global burden of disease and mortality.
- Teo Vignoli, Fabio Caputo, Roberta Agabio, Pierluigi Allosio, Maria Francesca Amendola, Sarino Aricò, Aniello Baselice, Patrizia Balbinot, Vito Antonio Campanile, Tiziana Fanucchi, Claudia Gandin, Livia Macciò, Paolo Enrico Carlo Marzorati, Cristina Meneguzzi, Davide Mioni, Andrea Noventa, Michele Parisi, Andrea Quartini, Mariano Quartini, Doda Renzetti, Maria Raffaella Rossin, Valeria Zavan, Paolo Cimarosti, Franco Marcomini, Valentino Patussi, Emanuele Scafato, Gianni Testino