陳建仁2006-07-252018-06-292006-07-252018-06-292003-07-31http://ntur.lib.ntu.edu.tw//handle/246246/4694Oral submucous fibrosis (OSF) is a chronic disease of oral mucosa, It can involve any part of oral cavity, sometimes, even the pharynx and esophagus. Its main characteristic is the abnormal accumulation of submucous collagen. Eventually, it may lead to oral mucosal stiffness trismus and dysphagia. These will severely impair patients’ eating, speaking, accessment of dental treatment, and quality of life. OSF is also an oral premalignancy. According to several long term follow-up studies, 2.3%~33.3% OSF will progress into oral cancer. The etiology of OSF remains unclear, and there is no effective clinical treatment for OSF. Prevention is more important than treatment for OSF. Most studies suggest betel quid chewing is an important risk factor for OSF, but only a small proportion of betel quid chewers get OSF. This implies that genetic susceptibility may also play an important role in the etiology of OSF. This project is to examine associations with OSF for genetic polymorphisms of repair gene, collagenase gene and cystatin gene, and to compare risk factors for OSF and oral cancer. Study subjects were recruited from hospital and communities. A total of 77 oral cancer patients, 167 OSF cases, 111 healthy betel quid chewers was recruited from the dental clinic of NTUH as our hospital subjects. We also recruited 173 healthy betel quid chewers from Makung, Chutung, Potzu, Kaoshu and Sanchi as our community controls. Standardized personal interviews-based on structure questionnaire was carried out to obtain information on risk factors for OSF and oral cancer. Polymerase chain reaction and restriction fragment length polymorphism was used to genotype the genes of collagen and collagenases and repair gene. Multiple logistic regression analysis was used to estimate multivariate-adjusted odds rations with their 95% confidence intervals of various risk factors. Among the 12 candidate gene loci, a biallelic promotor-region polymorphism of the TNFA gene at position –308 was found to have association with OSF. As precious study demonstrated the rare allele, TNF*2, having increased promotor function compared with the common allele, TNF*1 and the transcriptional induction of TNF-α in collagenase, we found the *2/ *2 genotype is more protective with an odds ratio of 0.4 (95% CI=0.2-0.7). This result is in keeping with a protective role of TNF-α against OSF. Moreover, the association between OSF and TNFA gene mentioned before was found to be independent of oral cancer.口腔黏膜下纖維化（oral submucous fibrosis, 以下簡稱OSF ）是一種慢性的口腔黏膜 病變，可侵犯口腔內任何部位的黏膜，有時甚至擴張至咽喉或食道，它的主要特徵是由於 口腔黏膜下膠原蛋白的異常堆積，最終導致病人口腔黏膜僵硬、張口困難及吞嚥困難，嚴 重影響病人的進食、說話及接受牙科醫療照護的便利性，大大地降低其生活品質。OSF 是 口腔癌前病兆的一種，根據國外之長期追蹤研究統計，OSF 患者有2.3%~33.3%會轉變成 口腔癌。 由於目前對於OSF 的病因尚不是很清楚，因此臨床上採用的治療方法是舒緩、改善 症狀或停止惡化，但無法完全回復黏膜之原貌。一般相信預防OSF 的發生要比治療OSF 來得重要。雖然大部分的研究皆建議經由減少不良習慣如嚼食檳榔，來降低OSF 的發生， 但是，只有少數吃檳榔的人會得到OSF ，其遺傳易感性可能扮演著重要的角色。引起OSF 的原因相當複雜，包括：嚼食檳榔、營養素缺乏、易感性、自體免疫等，至今尚不清楚。 這些疑問皆有賴近一步的疑問來釐清，並找出確定有效的預測因子來針對高危險群實施有 效率的預防介入措施。 本研究之主要目的為探討OSF 與膠原蛋白基因、代謝膠原蛋白基因及DNA 修補基因 的相關性研究，其目的為找出與OSF 相關的對偶基因或基因型，並估計各種基因型的頻 率，並且探討OSF 與口腔癌之危險因子，其目的為了找出OSF 與口腔癌之間危險因子的 差異。 本研究之研究對象分別來自醫院與社區；醫院部份，在台大醫院牙科部收集77 名口 腔癌患者、167 名口腔黏膜下纖維化病例及111 名健康之嚼食檳榔志願者。社區部份，在 馬公、竹東、朴子、高樹、三芝收集173 名健康之嚼食檳榔志願者，作為本研究之社區對 照。每名研究對象除了以結構式問卷進行標準化訪視獲取其危險因子暴露史外，並利用聚 合酵素連鎖反應和限制片段長度多形性分析，來測定個人膠原蛋白基因及其代謝基因及 DNA 修補基因之基因多形性。研究結果利用羅吉斯複迴歸分析方法來估計環境及遺傳危 險因子引起OSF 之危險對比值及其95%信賴區間，並進一步探討危險因子間的交互作用。 在12 個候選基因標記中，我們發現位於TNFA 基因促進子區域位置-308 的一個雙對 偶基因之多形性與OSF 有相關性存在。由於過去的研究發現此基因多形性中較稀少的對 偶基因TNF*2 比TNF*1 有較高的轉錄活性，且TNF-α有誘導collagenase 轉錄的功能， 而我們的研究*2/*2 基因形有較低之危險對比值（OR=0.4, 95%信賴區間=0.2-0.7 ），洽可解 釋TNF-α對OSF 的保護作用。再者，本研究發現的TNFA 基因與OSF 之間的相關與口腔 癌無關。application/pdf93347 bytesapplication/pdfzh-TW國立臺灣大學公共衛生學院流行病學研究所oral submucous fibrosis (OSF)association studyoral cancerrisk factorsgenetic polymorphismsgenotype frequency口腔黏膜下纖維化相關性研究口腔癌危險因子基因多形性基因形頻率[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/4694/1/912320B002084.pdf