Chen Ping-Ho, Wang Yen-Yun, Lan Ting-Hsun, Chan Leong-Perng, Yuan Shyng-Shiou
School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
Institute of Biomedical Sciences, National Sun Yat-Sen University, No. 70 Lienhai Road, Kaohsiung 804201, Taiwan.
Cancers (Basel). 2021 Jun 29;13(13):3268. doi: 10.3390/cancers13133268.
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 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; < 0.001). Compared to adjacent noncancerous tissues, a significant downregulation of MAO and COMT expression was exhibited in cancerous tissues ( < 0.01). Furthermore, in different cell models, MAO and COMT expression was significantly downregulated with an increased dose of arecoline ( < 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.
槟榔是第I类人类致癌物，会显著增加患口腔潜在恶性疾病（OPMD）以及口腔和咽癌的风险。本研究旨在探究单胺氧化酶（MAO）和儿茶酚-O-甲基转移酶（COMT）基因变异在口腔和咽癌以及OPMD风险评估中是否发挥潜在作用，尤其是在槟榔使用者中。我们采用病例对照研究，利用单核苷酸多态性来确认MAO和COMT的基因多态性。我们使用定量逆转录聚合酶链反应（qRT-PCR）、蛋白质免疫印迹法和免疫组织化学（IHC）来测定MAO和COMT的表达。携带MAOA rs6323 G等位基因、MAOB rs6324 G等位基因以及COMT rs4633 C/C基因型的个体患口腔和咽癌的风险显著增加（比值比[AOR]=56.99；P<0.001）。与相邻的非癌组织相比，癌组织中MAO和COMT的表达显著下调（P<0.01）。此外，在不同的细胞模型中，随着槟榔碱剂量的增加，MAO和COMT的表达显著下调（P<0.01）。在口腔和咽癌的个性化预防医学中，我们的研究结果首次证明了较低的MAO和COMT表达水平的潜在作用，以及将风险多态性用作临床生物标志物。
