Polymorphisms of acetaldehyde dehydrogenase 2 and alcohol dehydrogenase 1B on the malignant transformation of vocal cord leukoplakia: A Chinese cohort

Severe dysplasia of vocal cord leukoplakia (VCL) is more likely to occur in laryngeal carcinoma. Alcohol dehydrogenase and acetaldehyde dehydrogenase are both important enzymes in alcohol metabolism. This study aimed to investigate the incidence rate of malignant transformation in patients with VCL and the role of drinking habits and ALDH2 and ADH1B genetic polymorphisms in the malignant transformation of VCL. From January 2007 to January 2017, 136 cases of VCL were included in this retrospective analysis. Information on medical history, alcohol and tobacco consumption habits, ALDH2 and ADH1B genotypes, gastroesophageal reflux, and clinical pathological characteristics of VCL was collected. As a result, patients had a median follow-up of 9.6 years (interquartile range: 7.5-12.5 years). Twenty-three of 136 VCL patients finally developed laryngeal carcinoma, resulting in a cumulative malignant transformation rate of 16.9%. Cox regression analysis demonstrated that the independent risk factors for the malignant transformation of VCL included age over 60 years (hazard ratio [HR]: 13.872, p < 0.001), ALDH2 *2 allele status (HR: 9.694, p < 0.001), alcohol (HR: 10.011, p < 0.001) and tobacco (HR: 8.869, p < 0.001) exposure after operation, and drinking frequency (HR: 2.178, p = 0.016). Therefore, among patients over 60 years old, an ALDH2-inactivating mutation and excessive ethanol and tobacco consumption are potential contributors to the malignant transformation of VCL.