Genetic and Proteinic Linkage of MAO and COMT with Oral Potentially Malignant Disorders and Cancers of the Oral Cavity and Pharynx

SIMPLE SUMMARY: The prevention and treatment of cancers of the oral cavity and pharynx are currently important issues for national health. Currently, the incidence of oral cavity and pharynx cancers is globally the highest in Taiwanese men. Regarding the occurrence of oral cavity and pharynx cancers and oral potentially malignant disorders (OPMD), no report has ascertained how betel quid (BQ) can induce the expression of monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). We aimed to explore the role and clinical significance of specific markers of BQ exposure and human susceptibility to MAO and COMT. Our findings highlight the association of MAO and COMT biomarkers to risks of oral and pharyngeal cancers and OPMD. These novel findings will provide important strategies for disease prevention, early clinical diagnosis, and treatment effectiveness, and will offer a strong foundation to reduce BQ-related cancers of the oral cavity and pharynx and OPMD. ABSTRACT: Betel quid (BQ), a group I human carcinogen, strongly contributes to an increased risk of oral potentially malignant disorders (OPMD) and cancers of the oral cavity and pharynx. This study was conducted to discover whether monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) variants play a potential role in the risk assessment of oral cavity and pharynx cancers and OPMD, particularly among BQ users. We applied a case–control study to confirm the polymorphism of MAO and COMT using single-nucleotide polymorphisms. We used qRT-PCR, Western blotting, and immunohistochemistry (IHC) to determine MAO and COMT expression. Carriers of the MAOA rs6323 G-allele, MAOB rs6324 G-allele, and COMT rs4633 C/C-genotype had a prominently increased risk of oral cavity and pharynx cancers (AOR = 56.99; p < 0.001). Compared to adjacent noncancerous tissues, a significant downregulation of MAO and COMT expression was exhibited in cancerous tissues (p < 0.01). Furthermore, in different cell models, MAO and COMT expression was significantly downregulated with an increased dose of arecoline (p < 0.01). In personalized preventive medicine for oral and pharyngeal cancers, our findings are the first to demonstrate the potential role of lower MAO and COMT expression levels, with the risk polymorphisms utilized as clinical biomarkers.