Physiologic and molecular effects of alcohol in the esophagus: a narrative review.

Background and Objective: Alcohol use accounts for significant morbidity and mortality globally. A wide range of esophageal disorders have been associated with alcohol consumption, most concerning of which is esophageal squamous cell cancer (ESCC). Alcohol use has also been associated with exacerbation of gastroesophageal reflux disease (GERD) symptoms. Despite being one of the first organs to encounter this toxic agent, the molecular effects of alcohol on the human esophagus and the mechanisms by which alcohol exerts its effects on esophageal motility and carcinogenesis remain incompletely defined. The objective of this narrative review is to provide an overview of the effect of alcohol and its toxic metabolite acetaldehyde on cellular signaling, the microbiome, and motility in the esophagus, along with a discussion on the possible mechanisms by which alcohol use increases risk for ESCC. Methods: A literature search was performed using PubMed, Google Scholar, and Ovid MEDLINE for the period from inception to December 1, 2024. To identify all relevant literature, the following search terms were used: "Alcohol OR ethanol" AND "esophagus OR GERD OR gastroesophageal reflux OR reflux OR cancer OR EoE OR eosinophilic esophagitis OR signaling OR epithelium OR stroma OR fibrosis OR microbiome". Studies published in English with full available text were included. Key Content and Findings: This narrative review provides an overview of the effect of alcohol consumption on the human esophagus. The review highlights the dose-dependent risk of ESCC with alcohol use, with increasing risk with higher consumption; with evidence of increased risk even with the smallest amounts of alcohol consistent with the International Agency for Research on Cancer recognition of alcohol as a Group 1 carcinogen. The review also discusses the mechanisms of carcinogenesis, highlighting the role of acetaldehyde, as well as the non-malignant consequences of alcohol on the esophagus, including effects on cellular signaling, the microbiome, and gastro-esophageal reflux disease. Conclusions: Alcohol consumption continues to exert morbidity and mortality worldwide. Increasing awareness of the multitude of established and potential effects on the human esophagus will allow for rationale supporting at the very least the moderation of alcohol consumption.