Salivary gland carcinomas (SGCs) are a diverse collection of malignant tumors with marked differences in biological activity, clinical presentation and microscopic appearance. Although the etiology is varied, secondary radiation, oncogenic viruses as well as chromosomal rearrangements have all been linked to the formation of SGCs. Epigenetic modifications are any heritable changes in gene expression that are not caused by changes in DNA sequence. It is widely accepted that epigenetics plays an important role in SGC development.
The embryonic development of the tubulo-acinar exocrine organ known as the salivary gland begins between week 6 and week 8 of intrauterine life. Submandibular and sublingual glands originate in the embryonic endoderm, while the parotid gland is thought to develop from the oral ectoderm 
. Salivary glands have a two-tiered structure with luminal (acinar and ductal) and abluminal (myoepithelial and basal) cell layers. Rapid entry into the cell cycle makes these cells vulnerable to neoplastic transformation 
. Salivary gland carcinomas (SGCs) are uncommon compared to the other carcinoma types but are common in the context of head and neck tumours 
. Salivary gland carcinomas (SGCs) account for between 3–6% of all head and neck malignancies. The parotid gland is the most commonly involved, especially by benign type followed by the submandibular gland and the minor salivary glands. Among the malignant histological subtypes are mucoepidermoid carcinoma (MEC), carcinoma ex pleomorphic adenoma, intraductal carcinoma, acinic cell carcinoma, adenoid cystic carcinoma (ACC), and carcinosarcoma 
. Mucoepidermoid carcinoma is further classified into a low-grade and high-grade tumor where the treatment approaches are significantly differed. It is challenging to get earlier diagnosis of these SGCs and deliver adequate treatment due to existing high histological heterogeneity.
Salivary gland carcinomas (SGCs) are exceptionally rare, hence very little is known about their etiology. A few studies have reported that alcohol consumption, tobacco use, diet high in animal fat and low in vegetables, and heavy cell phone use are associated with an increased risk of SGCs 
. Radiation exposure (such as radiotherapy to the head and neck) and certain occupational exposures (such as silica dust, nickel alloy dust, asbestos, and rubber products manufacturing and mining) have also been implicated 
. A history of cancer 
and perhaps exposure to the human papillomavirus 
, Epstein Barr virus 
, and HIV 
have also been identified (Figure 1
Figure 1. Etiological factors of salivary gland carcinoma. Multiple factors are working together to drive SGC from a few aberrant cells to a tumour phenotype with the capacity to metastasis. Therefore, the optimum environment for malignant development is maintained by a complex interplay of genetic events, risk factors, and epigenetic mechanisms. All of these factors work together to promote an unstable genome and hence, promote cancer progression.
Epigenetic and genetic changes have been proposed as etiological variables, but there are yet few research investigating its function in SGT (Figure 2
. Epigenetic events can take the form of DNA methylation, alterations in the expression of non-coding RNAs such as microRNAs (miRNAs), or abnormalities in the structural modification of histones 
. Several cancers, including SGCs, develop and progress due to epigenetic alterations that cause considerable changes in gene expression 
. In addition, significant genetic alterations have been documented in all SGCs, and these alterations can be grouped according to their role in prediction, diagnosis and prognosis 
Figure 2. Salivary gland carcinomas can be affected by a number of epigenetic events that can alter the development and progression of the cancer.
2. Epigenetics Mechanisms
Epigenetics is a broad word that refers to molecular mechanisms that affect gene expression without altering the DNA base sequence. Transcription regulators, epigenetic writers, gene imprinting, histone modification as well as DNA methylation are important epigenetic processes implicated in gene expression alterations (Figure 2
. DNA methylation involves transformation of methylated cytosine by treatment with sodium bisulfite, into thymine and two distinct probes which used to target each site of CpG 
. Mechanism of histone modifications involves chemical post-translational modifications (PTMs) such as sumoylation, ubiquitylation, acetylation, phosphorylation as well as methylation, to the histone proteins, that causes chromatin structure to change or attract histone modifiers 
. Another epigenetic mechanism is genomic imprinting that impacts a small group of genes, resulting in monoallelic expression of genes which is parental specific origin in manner. Gene expression as well as genomic region compaction are controlled by epigenetic alterations, which are produced by specific enzymes called as “writers” and eventually identified by the effector proteins called as “readers” and removed by erasers, all of which together contribute to the regulation of gene transcription, and abnormalities can result in tumor formation as well as development 
. Additionally, the creation of a different research known as nutrigenomic results from epigenetic regulation via diverse nutritional substances