Combined effects of lncRNA <i>MIR17HG</i> polymorphisms and lifestyle-related risk factors on the development and progression of tongue squamous cell carcinoma

Oral squamous cell carcinoma is the most common malignancy of the oral cavity, with tongue squamous cell carcinoma (TSCC) being particularly prevalent worldwide. Evidence suggests that the long noncoding RNA, miRNA 17-92a-1 cluster host gene (MIR17HG), plays dual roles in tumor development. However, its clinical relevance and genetic variation in TSCC remain unclear. Analysis of data from TCGA revealed that MIR17HG expression is significantly upregulated in head and neck squamous cell carcinoma, particularly in male and Asian populations. The present study examined the association between MIR17HG single-nucleotide polymorphisms (SNPs) and TSCC progression in Taiwanese men. Four tagging SNPs (rs1428, rs7318578, rs17735387, and rs75267932) were genotyped through a TaqMan allelic discrimination assay. The results revealed that rs75267932 G allele carriers had a significantly elevated risk of developing large tumors in the dominant genetic model. This association was more prominent in patients exposed to one of the environmental carcinogens including betel quid, cigarette smoke, or alcohol. Smokers or drinkers carrying the rs75267932 variant were also likely to present with advanced disease. When patients with TSCC were stratified by exposure to all three lifestyle-related risk factors, the effect of rs75267932 on disease progression became the strongest. Conversely, non-betel-quid chewers or nonsmokers carrying the variant had a reduced risk of high-grade tumors. Overall, the effect of rs75267932 on TSCC progression was most pronounced in individuals exposed to lifestyle-related risk factors. These findings unveil gene-environment interactions in TSCC and highlight MIR17HG polymorphisms as potential biomarkers for risk assessment and disease monitoring in Asian men.