Applied Sciences
| Open Access |
DOI: Epigenetic Alterations in Oral Squamous Cell Carcinoma Among Non-Tobacco Chewers and Non-Smokers
Aratrika Banerjee , Amity Institute of Biotechnology, Amity University Uttar Pradesh Lucknow Campus, Lucknow, Uttar Pradesh, India Shatakshi Narang , Amity Institute of Biotechnology, Amity University Uttar Pradesh Lucknow Campus, Lucknow, Uttar Pradesh, India Sayali Mukherjee* , Amity Institute of Biotechnology, Amity University Uttar Pradesh Lucknow Campus, Lucknow, Uttar Pradesh, IndiaAbstract
While tobacco and alcohol have been associated with Oral Squamous Cell Carcinoma (OSCC), there is increasing and worrying evidence suggesting a growing incidence in young, non-tobacco users; and, these tumours have been characterized as not having the 'classic' carcinogen-driven mutational signatures. This suggests that other molecular mechanisms may be responsible; DNA methylation, the canonical epigenetic modification controlling gene expression, has been identified as an early, stable, and possibly reversible event in oral carcinogenesis, however its specific role in young non-tobacco-related OSCC has not been fully synthesized. Here, we critically review the current evidence for DNA methylation changes in young non-tobacco-related OSCC. Increasing evidence suggests recurring promoter hypermethylation of tumour suppressor genes involved in cell cycle control, apoptosis, DNA repair and cell adhesion, alongside global epigenome-wide methylation reprogramming that does not seem dependent on tobacco status. Crucially, these methylation changes have also been identified in histologically normal adjacent mucosa and salivary DNA, thereby suggesting field cancerisation through an epigenetic mechanism as an early event in OSCC pathogenesis. The presented evidence indicates that, in young non-tobacco users, epigenetics may be the initiating factor in OSCC pathogenesis rather than a subsequent response to exogenous carcinogens. Underscoring the fact that age- and exposure-specific epigenomic syntheses have not been made to date, this review concludes that well-powered, age-stratified, epigenome-wide and longitudinal analyses are urgently required; better understanding of the specific DNA methylation signature for this patient group may lead to the identification of non-invasive diagnostic biomarkers, refined risk stratification and a new pathway for epigenetically mediated therapies in young-onset OSCC.
Keywords
Oral squamous cell carcinoma (OSCC), DNA methylation, Epigenetics, Young-onset oral cancer, Non-tobacco-associated OSCC, Salivary biomarkers.
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