A Pilot Genome-Wide Association Study of Malignant Transformation of Oral Verrucous Hyperplasia

Objective: We conducted a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNPs) associated with malignant transformation in oral verrucous hyperplasia (OVH) patients. Methods: The genomic DNA used for SNP genotyping was extracted from the buffy coat. The primary trait of the GWAS was cancer-free survival, defined as beginning at the initial OVH diagnosis and ending at the first diagnosis of oral cancer, loss to follow-up, or the end of follow-up, whichever occurred first. For each SNP, the distributions of cancer-free survival were compared between minor allele carriers and non-carriers using the log-rank test, and an SNP with a significant difference was considered to be associated with OVH malignant transformation. Results: The GWAS identified seven genome-wide significantly associated SNPs (p < 10−7). Among them, four are located in long non-coding RNA genes (STX18-AS1, TARID, LOC124903183, and GNAO1-DT), two are located in protein-coding genes (LIMCH1 and ZBTB44), and the remaining one is located in a non-coding RNA gene (LOC105375416). For each SNP, the minor allele was associated with a higher risk of malignant transformation. Conclusions: This pilot GWAS suggests genetic contributions to OVH malignant transformation. These findings warrant validation in larger samples and replication across diverse populations in future studies. © 2025 John Wiley & Sons Ltd.