ALDH2 polymorphism, alcohol intake and the attributable burden of cancer in East Asia: systematic review, meta-analysis, and modeling study

Abstract

<h3>Background</h3><p>East Asian populations, where alcohol consumption is rising, has a high prevalence of the inactivated aldehyde dehydrogenase-2 (ALDH2) enzyme involved in alcohol metabolism. This study estimates the burden of alcohol-attributable cancer accounting for genotype-specific cancer risk and alcohol exposure.</p><h3>Methods</h3><p>We conducted a systematic review and meta-analysis of eight databases on cancer risk to derive alcohol dose-response curves by ALDH2 genotype. A simulation-based approach using the Global Burden of Disease modelling framework was applied to estimate the population attributable fraction (PAF), incidence, and disability-adjusted life- years (DALYs) lost to alcohol-attributable cancer.</p><h3>Findings</h3><p>We included 34 studies (66,655 participants) from China, Japan, and South Korea in the meta-analysis. Alcohol dose-response curves for liver, oesophageal, and oral cavity/pharynx cancer showed an increased risk for people with the inactivated ALDH2 genetic polymorphism, resulting in a higher burden of alcohol-attributable cancer compared to GBD estimates. Our methods estimated annual incidence of cancer of 230,177 cases, an underestimate of 69,596 cases compared to GBD estimates. Similarly, total DALYs lost annually was underestimated by 1.20 million.</p><h3>Interpretation</h3><p>The burden of liver, oesophageal, and oral cavity/pharynx cancer attributable to alcohol is underestimated in populations with the ALDH2 genetic polymorphism when compared to current estimates.</p>