To assess the DNA methylation pattern in tobacco users with and without oral squamous cell carcinoma

Abstract

To assess the DNA methylation pattern in tobacco users with and without oral squamous cell carcinoma newlineAbstract newlineOver 90% of all oral malignancies are oral squamous cell carcinomas (OSCC). The contributing risk factors include use of tobacco products (smoked and smokeless), areca nut, betel quid, alcohol, genetic and epigenetic alterations. In South-East Asia (India, Pakistan, Sri Lanka, Bangladesh, and Taiwan) and the Pacific (Melanesia and Papua New Guinea), OSCC is the most prevalent form of cancer. Worldwide, in 2020, 377,713 incident cases and 177,757 fatalities were caused by OSCC.2 OSCC typically occurs in individuals above 40 years of age as compared to younger ones. It affects men more frequently than women globally, 5.8 vs. 2.3 per 100,000, respectively.3 newlineOSCC tissues are in an immunosuppressive state. Immune checkpoint system, metabolic factors, metabolic circumstances, and infiltration of immune-suppressive cells including myeloid derived suppressive cells (MDSC), Tregs, M2 macrophages, and MDSC all contribute to the suppressive tumour immune microenvironment (TIME). Tumour cells suppress and escape the immune system by altering the expression of cell surface antigens and secreting substances that deactivate the immune system.92 Immune checkpoints are frequently used by cancer cells to evade the immune surveillance causing immune suppression and promoting tumour growth. Its physiological function is to preserve self-tolerance and restrict tissue collateral damage after immune responses. newlineCTLA-4 (cytotoxic T lymphocyte associated antigen 4) is one of the several immune checkpoint molecules that contribute to Treg-mediated immunosuppression. Epigenetics is a rapidly evolving and promising field as genetic changes are reversible. These epigenetic changes are influenced by external environment factors such as the use of tobacco, etc. DNA methylation-based models predicting risk can provide promising opportunities for customized risk screening and eventually prevention of oral cancer. Though the function of CT