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

Abstract

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 (Ptrend = 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.

Figure 1.. Kaplan Meier survival curves for drinking status in patients with head and neck squamous cell carcinoma. Five-year disease-free survival was 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 (logrank test, P = 0.088).

Figure 2.. Kaplan Meier survival curves for aldehyde dehydrogenase 2 (ALDH2) genotype in patients with head and neck squamous cell carcinoma. Five-year disease-free survival was 85.7% (95% confidence interval [CI], 53.9–96.2%) for ALDH2 Lys/Lys patients, 56.2% (95% CI, 47.4–64.1%) for ALDH2 Glu/Lys patients, and 50.5% (95% CI, 40.3–59.7%) for ALDH2 Glu/Glu patients (logrank test, P = 0.154).

Figure 3.. Kaplan Meier survival curves of disease-free survival for drinking status according to aldehyde dehydrogenase 2 (ALDH2) Glu/Glu genotype. Five-year disease-free survival among ALDH2 Glu/Lys patients was 63.6% (95% confidence interval [CI], 43.4–78.2%) for non-drinkers, 55.1% (95% CI, 40.8–67.3%) for light drinkers, 47.1% (95% CI, 25.2–66.3%) for moderate drinkers, and 56.8% (95% CI, 37.3–72.3%) for heavy drinkers (logrank test, P = 0.764). Respective rates among ALDH2 Glu/Glu patients were 59.4% (95% CI, 30.9–79.4%), 60.6% (95% CI, 44.8–73.2%), 44.6% (95% CI, 23.5–63.8%), and 21.1% (95% CI, 5.8–42.7%) (logrank test, P = 0.023).