The Role of Keratin-8 and Keratin-18 Polymorphisms and Protein Levels in the Occurrence and Progression of Vocal Leukoplakia

Abstract

Objective: This study aimed to evaluate the association between the single-nucleotide polymorphism (SNP) and tissue protein level of keratin-8/18 and the occurrence and progression of vocal leukoplakia. Methods: The case-control study enrolled 158 patients with vocal leukoplakia, 326 patients with laryngeal squamous cell carcinoma (LSCC), and 268 healthy controls, which were tested for genotype analysis with keratin-8 and keratin-18 gene polymorphisms using pyrosequencing. The tissue protein expression levels of keratin-8 and keratin-18 were evaluated using immunohistochemistry. Results: The keratin-8 SNP RS1907671 showed an obvious increased risk for vocal leukoplakia (OR 1.56, p = 0.002), while the other SNPs (RS2035875, RS2035878, RS4300473) were tested as protective factors for vocal leukoplakia and LSCC (OR <1, p < 0.05). In keratin-18 SNP test, both RS2070876 and RS2638526 polymorphisms demonstrated decreased risks for vocal leukoplakia and LSCC (OR <1, p < 0.05). The protein levels of keratin-8 and keratin-18 in vocal leukoplakia group were significantly higher than those of the LSCC group (p < 0.05). Conclusions: Keratin-8 and keratin-18 polymorphisms and protein levels are associated with the occurrence and progression of vocal leukoplakia.