Significance of Cytokeratin-1 Single-Nucleotide Polymorphism and Protein Level in Susceptibility to Vocal Leukoplakia and Laryngeal Squamous Cell Carcinoma

Abstract

Objective: To investigate the association between the cytokeratin (CK)-1 single-nucleotide polymorphism (SNP), the protein level of CK-1 and the risk of vocal leukoplakia and laryngeal squamous cell carcinoma (LSCC). Methods: In this case-control study, 155 patients with vocal leukoplakia, 323 patients with LSCC, and 266 healthy controls were genotyped for the CK-1 (SNP RS14024) gene using pyrosequencing. The protein expression level of CK-1 was analyzed in vocal leukoplakia, LSCC, and vocal polyp patients by immunohistochemistry (IHC). Results: Of the CK-1 RS14024 polymorphism, the heterozygote AG and homozygote GG genotype exhibited a significantly increased risk of LSCC (AG: OR = 2.16, p = 0.014; GG: OR = 2.15, p = 0.018) compared to normal controls. A higher protein expression level of CK-1 was detected in patients with LSCC compared to vocal leukoplakia and polyps (both p < 0.001), and a significant increasing trend of CK-1 protein expression level from mild-moderate dysplasia to moderate-severe dysplasia in vocal leukoplakia patients was also observed (p = 0.006). Conclusions: This study demonstrates that the CK-1 SNP and high protein expression levels are associated with vocal leukoplakia and LSCC and promote the transformation from vocal leukoplakia to LSCC in a Chinese Han population.