Novel Genetic Risk Variants Associated with Oral Tongue Squamous Cell Carcinoma

Head Neck Pathol. 2025 Apr 25;19(1):45. doi: 10.1007/s12105-025-01784-0.

ABSTRACT

PURPOSE: Limited data from genome-wide association studies (GWAS) focusing on oral tongue squamous cell carcinoma (OTSCC) are available. The present study was conducted to explore genetic associations for OTSCC.

METHODS: A GWAS on 376 cases of OTSCC was conducted using the FinnGen Data Freeze-12 dataset. The case-cohort included 205 males and 171 females. Cases with malignancies involving the base of the tongue or lingual tonsil were excluded from the case-cohort. Individuals with no recorded history of malignancy were used as controls (n = 407,067). A Phenome-wide association study (PheWAS) was performed for the lead variants to assess their co-associations with other cancers.

RESULTS: GWAS analysis identified three genome-wide significant loci associated with OTSCC (p < 5 × 10-8), located at 5p15.33 (rs27067 near gene LINC01511), 10q24 (rs1007771191 near RPS3AP36), and 20p12.3 (rs1438070080 near PLCB1), respectively. PheWAS showed associations of rs27067 mainly with prostate cancer (OR = 1.06, p = 5.41 × 10^-7), and seborrheic keratosis (OR = 1.11, p = 1.51 × 10^-11). A co-directional effect with melanoma was also observed (OR = 0.93, p = 6.24 × 10^-5).

CONCLUSION: The GWAS detected two novel genetic associations with OTSCC. Further research is needed to identify the genes at these loci that contribute to the molecular pathogenesis of OTSCC.

PMID:40278994 | DOI:10.1007/s12105-025-01784-0