Alcohol Flushing and Oral Cancer in Korea: A Propensity Score-Matched Case-Control Study

Background and aims Alcohol flushing is a phenotypic marker of aldehyde dehydrogenase-2 ( ALDH2 ) deficiency and may increase susceptibility to oral cancer through acetaldehyde accumulation. However, evidence specifically regarding primary oral cancer remains limited. Methods This propensity score matched case-control study included 74 patients newly diagnosed with primary oral cancer at Seoul National University Dental Hospital (July 2024-December 2025) and 296 healthy controls from the Korea National Health and Nutrition Examination Survey (2019-2021). Participants were matched 1:4 using propensity score matching for age, sex, and education. Smoking and alcohol consumption were adjusted as covariates in multivariable logistic regression models to minimize overmatching and evaluate potential interaction effects. Results A positive alcohol flushing response was independently associated with an increased risk of oral cancer (adjusted odds ratio [aOR] = 5.71; 95% confidence interval [CI]: 2.90-11.22). The association appeared stronger among never-smokers (aOR = 6.87) than ever-smokers (aOR = 5.97), suggesting that ALDH2 -related acetaldehyde exposure may be associated with oral carcinogenesis independently of tobacco exposure. In addition, ever-smokers with both a positive flushing response and heavy drinking habits showed an approximately 10-fold increased risk of oral cancer (aOR = 10.10; 95% CI: 1.77-57.71). Conclusions The alcohol flushing response was significantly associated with oral cancer risk, independent of smoking status. Individuals with combined exposure to flushing, smoking, and heavy alcohol consumption showed the highest associated risk observed in this study, suggesting that the flushing response may serve as a useful clinical marker for identifying individuals at elevated risk of oral cancer in East Asian populations.