# Novel Genetic Risk Variants Associated with Oral Tongue Squamous Cell Carcinoma

## TL;DR

This study identifies three genetic variants linked to oral tongue cancer and finds connections to other cancers like prostate cancer and seborrheic keratosis.

## Contribution

The study reports two novel genetic associations with oral tongue squamous cell carcinoma.

## Key findings

- Three genome-wide significant loci were identified for OTSCC at 5p15.33, 10q24, and 20p12.3.
- The variant rs27067 showed strong associations with prostate cancer and seborrheic keratosis.
- A co-directional effect with melanoma was observed for rs27067.

## Abstract

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.

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.

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).

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.

The online version contains supplementary material available at 10.1007/s12105-025-01784-0.