癌症為台灣地區十大死因之冠，而近年來口腔癌的發生率和死亡率正逐年增加中。口腔癌的發展是個多步驟的過程，需要累積多個基因變異，而基因變異受到患者的遺傳傾向和環境的影響。褪黑激素受體1A (melatonin receptors 1A; MTNR1A)是負責調節褪黑激素的下游作用且具有腫瘤抑制的效果。然而，MTNR1A基因多型性與罹患口腔癌風險之間的相關性仍尚未釐清。因此，本研究的目的在探討MTNR1A基因多型性和暴露在環境致癌物質的綜合效應對口腔癌的易感受性和臨床病理參數的影響。本實驗利用即時聚合酶鏈鎖反應(real-time polymerase chain reaction; real-time PCR)分析618名口腔癌患者和560名非癌症對照者的3個MTNR1A基因多型性。本研究發現MTNR1A基因多型性(rs2119882、rs13140012、rs6553010)其CTA單倍型罹患口腔癌的風險較高。此外，MTNR1A基因多型性顯示與環境因子(檳榔和香菸的使用)的協同作用有提高對口腔癌的易感受性的影響。最後，有嚼食檳榔習慣的口腔癌患者其MTNR1A rs13140012帶有T/T對偶基因有較高的風險發展成晚期的臨床分期和淋巴結轉移。這些結果支持MTNR1A基因多型性與吸菸和嚼食檳榔習慣之基因與暴露環境因子的交互作用可能改變口腔癌的易感受性和轉移。 Cancer has been the first leading cause of death in Taiwan and the incidence and mortality of oral cancer have been constantly increased during the last decade. The development of oral cancer is a multistep process requiring the accumulation of multiple genetic alterations, which is affected by a patient’s genetic predisposition and by environmental influences. The melatonin receptors 1A (MTNR1A) is responsible for mediating the downstream effects of melatonin, and have a tumor-suppressive effect. However, little is known about the association between genetic polymorphisms of MTNR1A and the risk of oral cancer. Therefore, the purpose of this study was to explore the combined effect of MTNR1A gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of oral cancer. Three polymorphisms of the MTNR1A gene from 618 patients with oral cancer and 560 non-cancer controls were analyzed by real-time polymerase chain reaction (PCR). The CTA haplotype of the studied MTNR1A polymorphisms (rs2119882, rs13140012, rs6553010) was related to a higher risk of oral cancer. Moreover, MTNR1A gene polymorphisms exhibited synergistic effects of environmental factors (betel quid and tobacco use) on the susceptibility of oral cancer. Finally, oral-cancer patients with betel quid-chewing habit who had T/T allele of MTNR1A rs13140012 were at higher risk for developing an advanced clinical stage and lymph node metastasis. These results support gene-environment interactions of MTNR1A polymorphisms with smoking and betel quid-chewing habits possibly altering oral-cancer susceptibility and metastasis.
