Chen Ping-Ho, Chung Chia-Min, Wang Yen-Yun, Huang Hurng-Wern, Huang Bin, Lee Ka-Wo, Yuan Shyng-Shiou, Wu Che-Wei, Lin Lee-Shuan, Chan Leong-Perng
School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Institute of Biomedical Sciences, National Sun Yat-sen University, No. 70 Lienhai Road, Kaohsiung 80424, Taiwan.
Diagnostics (Basel). 2020 Nov 21;10(11):982. doi: 10.3390/diagnostics10110982.
Betel quid (BQ) has been classified as a Group I human carcinogen in light of evidence demonstrating an association with an elevated risk of oral and pharyngeal cancers. To date, the incidence rate of oral and pharynx cancers among Taiwanese men ranks the highest worldwide. However, no study has yet confirmed variants of CYP26A1 was associated with the risks of oral and pharyngeal cancers. A case-control study was conducted (n = 339). CYP26A1 polymorphism was performed using SNP assay. Real-time qRT-PCR and Western blotting were used to determine the levels of CYP26A1 expression. The cancer cell model involved treatment with arecoline. Our findings showed that the downregulation of CYP26A1 mRNA and protein expression are more frequently observed in cancerous tissues than adjacent normal tissues in patients with oral and pharynx cancers ( < 0.01). We found that CYP26A1 was downregulated as the arecoline dose increased. We hypothesized that lower levels of CYP26A1 mRNA expression can be utilized a clinically biomarker causes oral and pharynx cancers. Arecoline appears to modulate CYP26A1 expression through specific pathways. Carriers of CYP26A1 SNP, rs2068888 (G/G)/rs4418728 (G/G) and who have lower levels of CYP26A1 expression are associated with an increased risk of oral and pharyngeal cancers.
鉴于有证据表明槟榔嚼块（BQ）与口腔癌和咽癌风险升高有关，它已被列为第I组人类致癌物。迄今为止，台湾男性的口腔癌和咽癌发病率在全球排名最高。然而，尚无研究证实细胞色素P450 26A1（CYP26A1）变体与口腔癌和咽癌风险相关。进行了一项病例对照研究（n = 339）。使用单核苷酸多态性（SNP）检测进行CYP26A1基因多态性分析。采用实时定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测CYP26A1表达水平。癌细胞模型采用槟榔碱处理。我们的研究结果表明，在口腔癌和咽癌患者中，癌组织中CYP26A1 mRNA和蛋白表达下调的情况比相邻正常组织更常见（P < 0.01）。我们发现随着槟榔碱剂量增加，CYP26A1表达下调。我们推测CYP26A1 mRNA表达水平降低可作为导致口腔癌和咽癌的临床生物标志物。槟榔碱似乎通过特定途径调节CYP26A1表达。CYP26A1单核苷酸多态性rs2068888（G/G）/rs4418728（G/G）的携带者以及CYP26A1表达水平较低者患口腔癌和咽癌的风险增加。
