口腔癌(oral cancer)是發生在口腔的惡性腫瘤之總稱，可出現在口腔的任何部位，大多數是由黏膜上的鱗狀細胞惡化而成，在台灣地區以舌癌與頰黏膜癌佔大多數。口腔鱗狀細胞癌的特性具有高度侵襲性並且容易轉移到淋巴結，罹患後病人的預後差及存活率低，因此我們需要更清楚了解口腔癌造成高度侵襲的機制，才能有效的預防及治療。基質金屬蛋白水解(matrix metalloproteinase，MMP)在正常細胞中主要參與細胞外基質重組，使正常組織生長以及分化。在癌症方面，主要是與癌症細胞的惡性化程度有關，牽涉到使腫瘤快速生長、侵襲，以及藉著將細胞外基質裂解而進行轉移作用。MMP-14通常表現在癌細胞的表面，是一種可以促進侵襲的蛋白質水解，由於MMP-14位於侵犯性癌細胞的前緣，所以可以將大多數組織的障壁(barrier)組成物質裂解。目前研究已發現許MMP-14的基因多型性位置，但並沒有關於MMP-14的基因多型性與口腔癌的相關研究。因此本研究的目的在於探討MMP-14之基因多型性是否與口腔癌的罹患易感性有關，以及是否與口腔癌患者的疾病嚴重程度有相關性。我們收集347位口腔癌患者與253位非癌症之對照組，分析抽菸、喝酒、嚼檳榔等習慣與口腔癌的影響，接著利用PCR-RFLP分別進行MMP-14 -165 G/T、+7096 T/C 與+8153 G/A之基因多型性分析。同時也分析MMP-14之基因多型性與口腔癌相關臨床參數，包括臨床分期、腫瘤大小、淋巴結轉移、細胞分化狀態等的關係。統計分析發現，MMP-14基因+7096位置上的變異在口腔癌病例與對照組之間基因頻率的分佈具有顯著差異(P<0.001)，具有至少一個T對偶基因者，罹患口腔癌的比例較完全不帶T者罹患口腔癌的比例高 (P=0.012)，且腫瘤容易大於T2期。在MMP-14 +8153位置上攜帶A對偶基因罹患口腔癌的比例較攜帶G對偶基因罹患口腔癌的比例高 (P=0.034)。因此我們認為，MMP-14之基因多型性與中台灣族群罹患口腔癌的易感性有關，可被視為口腔癌的發生及病理上促進口腔癌惡化的可能因子。
Oral cancer is the sixth leading cause of cancer death in Taiwan, and more than 85~90 % of cases are oral squamous cell carcinoma (OSCC). It is characterized by a high degree of local invasiveness and metastasis to cervical lymph nodes. The poor prognosis and survival rate of patients presenting with advanced disease underscores the need to better understand the molecular mechanisms of invasion in oral cancer. MMP-14 is an important player in wound healing, bone development, angiogenesis, inflammation and tumor invasion. MMP-14 also plays an important role in the development and resolution of experimental oral cancer. Several studies have demonstrated association between MMP-14 gene polymorphisms and various diseases. However, there is no research on the association of polymorphisms in MMP-14 gene with oral cancer. Thus, we investigated through a case-control study performed for three single nucleotide polymorphisms (SNPs) located in the promoter region or the exons of MMP-14 gene in order to investigate the association between these SNPs and the development of oral cancer. 253 oral cancer patients and 347 controls were recruited. SNPs of MMP-14 gene located at -165, +7096, and +8153 sites were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. In this study, the genotype frequency of MMP-14 +7096 C/T were significantly different between oral cancer patients and controls(P<0.001). Participant who carried MMP-14 +7096 haplotype T have a higher susceptibility of oral cancer. The oral cancer patients with at least one T allele of MMP-14 gene had a higher risk lead to tumor size progress to stage III or IV. The MMP-14 +8153 A (P=0.034) had a significantly higher frequency in the oral cancer group than the control group. These results have demonstrated a significant association of gene polymorphisms in the MMP-14 gene and susceptibility with oral cancer. Furthermore, the haplotype of the MMP-14 +7096 T and +8153 A might be involved in the pathogenesis of oral cancer.
