Aldehyde Dehydrogenase 2 Deficiency and Associated Health Risks in East Asian Populations: An Overview

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Asatani Z, Brooks A


When alcohol is consumed, Alcohol dehydrogenase metabolizes ethanol to a toxic metabolite called acetaldehyde. Mitochondrial Aldehyde dehydrogenase 2 (ALDH2) is an enzyme produced by the liver that metabolizes acetaldehyde to a significantly less toxic acetate. Approximately, 30-40% of the Asian population have an inherited deficiency for aldehyde dehydrogenase 2, resulting in the accumulation of acetaldehyde. The facial flushing response secondary to alcohol consumption is a key biomarker for ALDH2 deficiency. This study focuses on the increased risk of esophageal cancer in East Asian populations with ALDH2 deficiency. In this review, 67 PubMed articles within the last 30 years were reviewed. Each article was based on studies that excluded animal preclinical work. Test subjects were limited to East Asian populations with and without the ALDH2*2 deficiency. Ethanol affects epigenetic methylation and acetylation patterns, which are important regulators of gene expression. Ethanol-induced hypomethylation can activate the expression of oncogenes which can result in malignant transformation. Clinicians can utilize patient data to customize treatment plans tailored to their patients who come from cultural backgrounds and have increased genetic and epigenetic risks. Recent studies have provided insight to what preventative strategies can be implemented to increase health outcomes and life expectancy in patients with ALDH2 deficiency. Further research should utilize prior risk assessment models to enhance ALDH2 screening techniques and ALDH2 deficient patient surveillance. There remain several gaps in research, including the role of ALDH in oncogenic signaling pathways and its use as a biomarker in cancer development or metastasis and surgical efficacy techniques in esophageal cancer treatment.

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