Association Between Alcohol Dehydrogenase Polymorphisms and the Recurrence of Laryngeal Carcinoma

Objectives Alcohol consumption is closely associated with prognosis for laryngeal squamous cell carcinoma (LSCC) patients. As key enzymes in ethanol metabolism, proteins in the alcohol dehydrogenase (ADH) family make for valuable targets to establish a novel predictive nomogram model. This study attempts to do so by focusing on the single nucleotide polymorphisms (SNPs) of ADH1B and ADH1C in LSCC. Methods Sixty eight LSCC patients that were followed up for more than 10 years were retrospectively analyzed. Endpoints of the current study included disease-free survival and overall survival. Survival analyses were performed using the Kaplan-Meier method and evaluated by log-rank test. The prognostic value of eight ADH1B SNPs and three ADH1C SNPs were evaluated using univariate and multivariate Cox regression analyses. A nomogram model for disease-free survival was established and evaluated using the receiver operating characteristic curve, the C-index, and a calibration plot. Results Significant association was exhibited between rs17033 (p < 0.001) and rs1229984 (p = 0.002) with an increase in LSCC recurrence rate on Kaplan-Meier curves. Multivariate logistic regression analysis revealed that the rs17033 polymorphism of ADH1B was independently associated with an increased risk of LSCC recurrence (HR = 3.325, 95% CI = 1.684-6.566, p = 0.001). Based on these findings, a prognostic nomogram of LSCC patients involving ADH1B rs17033 was constructed. Conclusion This study has demonstrated an independent association between ADH1B gene variants and the recurrence of LSCC. A nomogram model based on rs17033 of ADH1B, age, T, and N stages were successfully developed for the first time to predict the probability of recurrence in LSCC patients. Level of Evidence III Retrospective cohort study Laryngoscope, 2022