ArticleActa odontologica Scandinavica2025
Evidence of mutations in tumour suppressor genes among oral cancer in Naswar, smokeless tobacco users.
Article in Acta odontologica Scandinavica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveSmokeless tobacco has been linked to the genetic modification of oral squamous cell carcinoma (OSCC). Our study aims to further investigate the disease among Naswar users at the genomic level to understand genetic diversity and discover new targeted therapy.
methodsA multi-centre descriptive cross sectional research was designed comprising a total of 80 cases of OSCC who were habitual users of Naswar. Out of the 80 cases, whole exome sequencing (WES) was applied to 7 formalin fixed paraffin embedded (FFPE) tissues of OSCC. We further investigated immunohistochemical expression of mutant TP53 and CDKN2A protein in tissues of 80 OSCC samples. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 19.
resultsAmong the total 2,216 somatic variants identified in tumour suppressor genes (TSGs), we compared the high frequency mutation genes reported in OSCC in Catalogue of Somatic Mutations in Cancer (COSMIC) database with research samples, and found that TP53 (85.7%), NOTCH1 (85.7%), and FAT1 (85.7%) showed higher rate of mutation. Among single nucleotide variants, higher prevalence of C/T and G/A base change was noted. Interestingly, a distinct panel of 12 genes was detected to be mutated in 100% samples which was not previously reported compared to Single Nucleotide Polymorphism Database (dbSNP). PTPRT mutation (rs2867655) was present in seven samples and IGF2R (rs629849) was seen in two samples. A statistically significant relation was observed between mutant TP53 protein expression and duration of Naswar use and clinical stages while difference in CDKN2A protein expression was found to be statistically significant with respect to stage only.
conclusionsOur study presented preliminary data of genetic aberrations in patients exposed to known risk factor (Naswar). These findings can enhance the understanding of genetic aetiology and serve as basis for innovative targets of therapy.
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