Aldehyde Dehydrogenase 2 Polymorphism Is a Predictor of Smoking Cessation

Introduction: Smoking cessation has been known to be associated with drinking behaviors, which are influenced by polymorphisms in genes encoding alcohol metabolizing enzymes. The aim was to evaluate the impact of aldehyde dehydrogenase 2 (ALDH2, rs671) and alcohol dehydrogenase 1B (ADH1B, rs1229984) polymorphisms together with drinking behaviors on smoking cessation. Methods: We conducted a cross-sectional study with 1137 former smokers and 1775 current smokers without any cancer at Aichi Cancer Center Hospital between 2001 and 2005. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for successful smoking cessation by comparing former smokers (quitters) with current smokers (non-quitters). Results: Older age, lower amount of cumulative smoking exposure, lower number of cigarettes per day, younger age of smoking initiation, shorter smoking duration, longer time to first cigarette in the morning, and lower amount of drinking among ever drinkers were predictors of smoking cessation. After careful adjustment for age, sex, smoking patterns, and drinking status, the ORs for smoking cessation among subjects with ALDH2 Glu/Lys and Lys/Lys were 1.02 (95% CI 0.84-1.23) and 1.78 (95% CI 1.23-2.58) compared with those with ALDH2 Glu/Glu, respectively Mediation analyses confirmed that the effect of ALDH2 Lys/Lys on smoking cessation was independent by dinking behaviors. No statistically significant association between ADH1B polymorphism and smoking cessation was observed. Conclusions: In our Japanese population, ALDH2 polymorphism predicts smoking cessation, independent by drinking behaviors. Interventions for promoting smoking cessation by ALDH2 polymorphism may be useful in Asian populations. Implications: We newly show that subjects with ALDH2 Lys/Lys genotype in a functional polymorphism, rs671, are more likely to quit smoking than those with ALDH2 Glu allele in a Japanese population. Our finding suggests that ALDH2 polymorphism may be useful for promoting smoking cessation in those specific populations as East Asian ones with frequent ALDH2 Lys allele carriers.