Impact of FOSL1 polymorphisms and expression on disease progression in oral tongue squamous cell carcinoma

Oral tongue squamous cell carcinoma (OTSCC) is the most common subtype of oral cancer, with betel quid chewing, tobacco smoking, and alcohol consumption recognized as major risk factors. This study investigated the associations between FOSL1 single-nucleotide polymorphisms (SNPs) and disease susceptibility and clinicopathological characteristics in OTSCC patients. Three FOSL1 SNPs (rs637571, rs653914, and rs10896065) were genotyped in 377 male OTSCC patients and 1,194 controls using real-time polymerase chain reaction. The FOSL1 rs10896065 polymorphic T variant was significantly associated with advanced clinical stage (Stage III-IV; AOR = 1.663, 95% CI = 1.059-2.611, p = 0.027) and larger tumor size (AOR = 1.813, 95% CI = 1.162-2.831, p = 0.009). Among betel quid chewers, carriers of the CT+TT genotype showed significant associations with advanced clinical stage, larger tumor size, and moderate-to-poor tumor differentiation. Similar associations with advanced stage and greater tumor size were observed among smokers carrying the CT+TT genotype. Analysis of The Cancer Genome Atlas dataset further demonstrated that elevated FOSL1 mRNA expression was significantly associated with larger tumor size (T3-T4 vs. T1-T2, p = 0.0216). These findings suggest that the FOSL1 rs10896065 T allele is associated with advanced clinicopathological features in OTSCC patients, particularly among betel-quid chewers and smokers. FOSL1 polymorphisms may have potential as biomarkers associated with clinicopathological characteristics in OTSCC.