Abstract
Betel quid (BQ) chewing increased the risk of oral cancer and oral submucous fibrosis (OSMF), an oral premalignant disorder (OPMD) with malignant transformation potential. BQ components such as areca nut (AN), trauma by coarse AN fiber, catechin, copper, alkaloids, stimulated reactive oxygen species (ROS), inflammation and cytotoxicity are suggested to be the contributing factors. They may induce tissue inflammation, proliferation of fibroblasts and collagen deposition, myofibroblast differentiation and contraction, collagen cross-links and inhibit collagen phagocytosis, finally leading to the development of OSMF and oral cancer. These events are mediated by BQ components-induced changes of extracellular matrix (ECM) turnover via regulation of TGF-β1, plasminogen activator inhibitor-1 (PAI-1), cystatin, lysyl oxidase (LOX) and tissue inhibitors of metalloproteinases (TIMPs) and metalloproteinases (MMPs). Genetic susceptibility is also involved in these disease processes. Further understanding the molecular mechanisms of BQ-induced OSMF and oral cancer can be helpful for future disease prevention and treatment.
Highlights
The contributory role of areca nut (AN) components to the pathogenesis of Oral Submucous Fibrosis (OSMF) is closely associated with the induction of reactive oxygen species (ROS) production [18], chronic mucositis, ulcers caused by mechanical trauma from coarse AN fibers [19,20], activation of the coagulation system [21], cytotoxicity to oral epithelial cells [8], stimulation of fibroblast proliferation/contraction [22,23], collagen synthesis/deposition [22,24], myofibroblast differentiation [10], tissue inflammation [9,25] and the inhibition of collagen degradation and phagocytosis [26,27].These AN components include AN extract (ANE), areca alkaloids, catechin, catechol and copper (Figures 1 and 2)
Lin et al (2004) assessed the association of metalloproteinases (TIMPs) and metalloproteinases (MMPs)-2 genotype with the risk of OSMF and oral squamous cell carcinoma (OSCC) by comparing 58 OSMF cases, 121 OSCC cases and 147 controls. Their data suggested no significant association between subjects carrying the CC genotype and the development of OSMF, but the results showed that subjects carrying the CC genotype had a two-fold increased risk for developing OSCC when compared with the CT or TT genotypes [70]
The results revealed that no significant difference in MMP-2 (−1306 C/T) and MMP-9 (−1562C/T) polymorphism occurred in OSMF patients compared to healthy controls, whereas the T allele showed a significant association with increasing progression of clinicopathological grading in head and neck squamous cell carcinoma (HNSCC) [58]
Summary
OSMF is defined as an insidious chronic disease affecting any part of the oral cavity and sometimes pharynx. The contributory role of AN components to the pathogenesis of OSMF is closely associated with the induction of ROS production [18], chronic mucositis, ulcers caused by mechanical trauma from coarse AN fibers [19,20], activation of the coagulation system [21], cytotoxicity to oral epithelial cells [8], stimulation of fibroblast proliferation/contraction [22,23], collagen synthesis/deposition [22,24], myofibroblast differentiation [10], tissue inflammation [9,25] and the inhibition of collagen degradation and phagocytosis [26,27].These AN components include AN extract (ANE), areca alkaloids (arecoline, arecaidine, guvacoline, guvacine), catechin, catechol and copper (Figures 1 and 2). The relationship between gene and OSMF is still uncertain and awaits clarification
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