Prognostic Value of Drinking Status and Aldehyde Dehydrogenase 2 Polymorphism in Patients With Head and Neck Squamous Cell Carcinoma

Background: The association between alcohol drinking, aldehyde dehydrogenase 2 (ALDH2) polymorphism, and survival in patients with head and neck squamous cell carcinoma (HNSCC) remains unclear. Methods: We performed a retrospective cohort study of 267 HNSCC patients at Aichi Cancer Center. Of these, 65 patients (24%) were non-drinkers, 104 (39%) were light drinkers (ethanol < 46 g or < 5 days/week), 46 (17%) were moderate drinkers (ethanol intake 46-68 g/day and >= 5 days/week), and 52 (20%) were heavy drinkers (ethanol intake >= 69 g and >= 5 days/week). The prognostic value of pre-treatment drinking status and ALDH2 polymorphism was investigated using multivariate proportional hazard models. Results: Drinking status was associated with disease-free survival (DFS) in HNSCC patients, with marginal statistical significance (5-year DFS: 67.9% [95% confidence interval {CI}, 53.8-78.4%] for non-drinkers, 57.6% [95% CI, 47.4-66.6%] for light drinkers, 46.1% [95% CI, 30.8-60.1%] for moderate drinkers, and 43.5% [95% CI, 29.3-56.9%] for heavy drinkers; P = 0.088). However, this association lost significance when multivariate analyses were adjusted for established prognostic factors. ALDH2 genotype was not significantly associated with DFS in HNSCC patients (5-year DFS: 85.7% [95% CI, 53.9-96.2%] for Lys/Lys, 56.2% [95% CI, 47.4-64.1%] for Glu/Lys, and 50.5% [95% CI, 40.3-59.7%] for Glu/Glu; P = 0.154). After stratification by ALDH2 genotype, we observed a significant positive dose-response relationship between drinking status and DFS in HNSCC patients with ALDH2 Glu/Glu (P-trend = 0.029). Conclusions: In this study, we identified a significant positive dose-response relationship between pre-treatment drinking status and DFS in HNSCC patients with ALDH2 Glu/Glu. To confirm this association, further study is warranted.