Analysis of single nucleotide polymorphism of SYNE1 gene in Oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of the major causes of cancer-related mortality in Taiwan and is strongly associated with alcohol consumption, betel quid chewing, and cigarette smoking. Spectrin repeat-containing nuclear envelope protein 1 (SYNE1) is downregulated in various cancer types, but its role in OSCC remains unclear. The aim of the present study is to investigate the association between single nucleotide polymorphisms (SNPs) of SYNE1 gene (rs2295190, rs2306916, rs2695261, rs9371601) and OSCC susceptibility as well as clinical outcomes in 377 OSCC patients and 480 cancer-free controls. No significant association was found between any of the four SNPs and overall OSCC risk. However, in OSCC patients, SYNE1 rs2295190 GT+TT genotype was significantly associated with advanced clinical stage (Stage III/IV) compared to the GG genotype (AOR=2.271, 95% CI: 1.081-4.771, p=0.030). This association was particularly evident in betel nut chewers (OR=2.399, 95% CI: 1.026-5.609, p=0.043) and in those using the areca nut with slaked lime and piper betel leaf (OR=3.482, 95% CI: 1.063-11.408, p=0.039). Although no significant association was observed between the four investigated SNPs and overall OSCC susceptibility, the SYNE1 rs2295190 GT+TT genotype was significantly associated with advanced clinical stage in OSCC patients. This association was more evident among individuals with betel nut chewing habits, mostly in OSCC patients who consumed areca nut with slaked lime and piper betel leaf. These findings suggest that SYNE1 rs2295190 may be associated with OSCC progression rather than overall disease susceptibility, particularly in the context of betel quid exposure.