Molecular mechanisms of oral submucous fibrosis and oral cancer: A review

Abstract

Chewing betel quid (BQ) increases the risk of oral cancer and oral submucous fibrosis (OSMF), a potentially malignant oral premalignant condition (OPMD). BQ constituents including areca nut (AN), trauma by coarse AN fibre, catechin, copper, alkaloids, increased reactive oxygen species, inflammation, and cytotoxicity are hypothesised to be the causative factors. They may stimulate tissue inflammation, fibroblast proliferation and collagen deposition, myofibroblast differentiation and contraction, collagen cross-links, and impede collagenphagocytosis, ultimately leading to the formation of oral squamous cell carcinoma (OSMF) and oral cancer. Through modulation of transforming growth factor1, plasminogen activator inhibitor1, cystatin, lysyl oxidase, tissue inhibitors of metalloproteinases, and matrix metalloproteinases, BQ componentinduced alterations in extracellular matrix turnover facilitate these events. In addition, genetic predisposition plays a role in many disease processes. Understanding the molecular pathways underlying BQinduced OSMF and oral cancer can aid in the future prevention and treatment of disease.This paper provides a comprehensive review of the molecular processes involved in BQ-induced OSMF and oral cancer, as well as future preventative prospects.