Wine consumption and oral cavity cancer: Friend or foe, two faces of Janus

The health benefits of moderate wine consumption have been extensively studied during the last few decades. Some studies have demonstrated protective associations between moderate drinking and several diseases including oral cavity cancer (OCC). However, due to the various adverse effects related to ethanol content, the recommendation of moderate wine consumption has been controversial. The polyphenolic components of wine contribute to its beneficial effects with different biological pathways, including antioxidant, lipid regulating and anti-inflammatory effects. On the other hand, in the oral cavity, ethanol is oxidized to form acetaldehyde, a metabolite with genotoxic properties. A review, authored by Paula Silva, Norbert Latruffe and Giovanni de Gaetano and published in the journal Molecules gives a critical compilation of both the beneficial and the detrimental effects of wine consumption on oral cavity cancer.
At the experimental level, some studies were carried out to explore ethanol’s carcinogenic mechanisms whereas others analysed the phenolic protective mechanisms. In the former group, the in vivo bio-kinetic studies were mainly focused on the analysis of salivary acetaldehyde.
Wine contains acetaldehyde in varying levels dependent on type (concentration is lower in red wine than white wine), but in addition to this, one of the key mechanisms in the oral formation of acetaldehyde is the metabolism of ethanol by the microbial flora of the oral mucosa. Acetaldehyde resulting from wine intake damages oral mucosa, which promotes the stimulation of cell regeneration. The various alterations in DNA can result in the development of a pre-malignant or a potentially malignant oral epithelial cell characterized by the ability to proliferate in a non-controlled mode. In fact, acetaldehyde leads to the overexpression of oncogenes and/or the silencing of tumor suppressor genes.
In contrast, the chemo-preventive/therapeutic properties of phenolic compounds against oral carcinogenesis were mainly studied using in vitro and in vivo test systems. Wine contains a number of phenolic compounds such as catechin, quercetin and resveratrol as well as anthocyanins that have been the focus of these studies
Several studies showed that polyphenols activate the p53 tumor suppressor gene. This could explain the induction of cell cycle arrest and apoptosis by polyphenols that was reported in some studies. Acetaldehyde’s genotoxicity also results in the formation of DNA adducts, which can also be reduced by polyphenols, as observed with black raspberry administration in vivo. On the other hand, polyphenols are potent antioxidants and, therefore, they counteract ROS/RNS generation due to an increase in CYP2E1 activity as promoted by ethanol consumption. Likely, the phenolic compounds from wine mitigate the deleterious effects of ethanol, decreasing the risk of OCC.
The authors state that although all these studies have yielded important data for understanding the mechanisms of action of either ethanol or phenolic compounds on either normal or tumor keratinocyte cells from the oral cavity, much remains to be studied. More adequately powered, randomised, placebo-controlled human studies, as well as experimental animal models, are required for a better understanding of the effect(s) of wine, particularly when consumed regularly in moderate doses, on oral cells.
In conclusion, this area warrants further investigation as a new way of thinking, which is to assess the wine-specific intake risk while considering the additive/synergistic or contrasting effects of its different compounds.
Source: Silva P, Latruffe N, Gaetano G. Wine Consumption and Oral Cavity Cancer: Friend or Foe, Two Faces of Janus. Molecules. 2020;25(11):E2569. Published 2020 May 31. open access.