上皮細胞黏著因子其基因多型性與口腔癌之相關性探討

上皮細胞黏著因子 (E-cadherin) 為細胞與細胞之間維持構型的重要蛋白，當細胞表面的 E-cadherin 出現變異時，細胞與細胞之間的交互作用便會失去功能，造成細胞異常的增生以及分化，研究顯示當細胞內的 E-cadherin 表現量降低時，細胞整體表現趨向癌化。文獻提及 E-cadherin 啟動子區域的基因多型性會影響 E-cadherin 的表現，但目前 E-cadherin 啟動子區域的基因多型性與口腔癌的相關性仍有許多地方尚未釐清。因此在本篇研究中，我們選取了 347 個對照組以及 251 個口腔癌的患者，對於其基因上游啟動子區域 160 C/A 及 347G/GA 位置上的基因多型性，利用聚合酶連鎖反應-限制片段長度多型性 (PCR-RFLP) 的方法進行分析及探討。在初步結果中，我們發現基因上游啟動子區域 160 處攜帶 AA 基因型相較於攜帶 CC 基因型的個體，具有較低罹患口腔癌的風險。而在基因上游啟動子區域 347 處攜帶 GG 的基因若插入 A allele 成為 GA/GA 基因型相較於 GG 基因型則具有較高罹患口腔癌的風險。同時將這些基因多型性與臨床資料進行配對分析，結果顯示基因多型性與臨床指標之間無直接相關性。另外，利用邏輯式迴歸加以分析，排除檳榔嚼食與抽菸對口腔癌發生率的影響，進一步釐清基因多型性與口腔癌的相關性。綜合以上結果顯示，當基因上游 347 處發生變異時，具有較高罹患口腔癌風險，而基因上游 160處發生變異時，則大幅降低罹患口腔癌的風險。另外於腫瘤大小、淋巴結的轉移、臨床期數、腫瘤分化之間做相關性的探討，並無統計學上的意義。而未來我們可以針對口腔癌病患復發與否及其存活率與此基因多型性來做進一步的探討。

關鍵字

口腔癌；鈣黏蛋白啟動子區域；單一核甘酸多型性

並列摘要

E-cadherin plays a critical role in cell-cell adhesion and establishment and maintenance of epithelial integration. A reduced expression or genetic mutation in E-cadherin would lead to the dysfunction in cell-cell interaction, cellular differentiation and proliferation. As a result, the reduced level of E-cadherin may lead to the formation of cancerous cells. Previous researches have discovered the predominant influence of promoter region on the expression level of E-cadherin, which has not been explored in the cases of oral cancer. In this study, 347 controls and 251 oral cancer patients were recruited and their genomic DNA samples were extracted from blood samples and then subjected to polymerase chain reaction – restriction fragment length polymorphism study for 160C/A and 347G/GA polymorphism within the upstream promoter region. Results revealed a significant association at 160 with A-allele carrying a lower risk (OR=0.33; 95% CI=0.18-0.58) for oral cancer, and 347GA-allele (OR=2.24; 95% CI=1.05-5.54) carrying a higher risk. Further statistical analysis for clinical characteristics revealed that these polymorphisms had no significant impact on these clinical features. To adjust for certain well-known oral cancer risk factors, including betel chewing, cigarette smoking and liquid drinking, logistic regression was performed to confirm that the -160C/A and -347G/GA polymorphism of E-cadherin has direct effect on the risk of Taiwan oral cancer. Furthermore, no significant association between E-cadherin polymorphism and tumor size, lymph node metastasis, clinical stage, differentiation of oral cancer patients was found.

並列關鍵字

oral cancer ； E-cadherin promoter region ； Single nucleotide polymorphisms

參考文獻

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上皮細胞黏著因子其基因多型性與口腔癌之相關性探討

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