鄭玉娟2006-07-252018-06-292006-07-252018-06-292004-07-31http://ntur.lib.ntu.edu.tw//handle/246246/4702DNA 修補基因多形性與癌症的 發生，是近年來分子生物研究重視的 課題之一，本研究藉由分子流行病學 方法，首度探討DNA 的修補基因 hMLH1 、LIG1 基因多形性與環境因子 共同作用時，發生鼻咽癌之關係。 中國人之鼻咽癌發生率居全世界 之冠，比白人高出20 到30 倍，亦高 出日本人或韓國人甚多。相較於其他 癌症，鼻咽癌是屬較早發之癌症且好 發於男性，一旦發病對社會之衝擊是 不可忽視的。本計劃將著重於國人特 有之鼻咽癌危險因子之分析，並以病 例對照研究探討鼻咽癌環境致癌物與 基因之交互作用。其研究對象是來自 民國80 年7 月至83 年12 月，由台大 醫學院、台大公共衛生學院與美國國 立癌症研究院共同合作之鼻咽癌病例 對照研究，在台大及馬偕醫院共收集 335 名經病理確診之新病例,年齡在75 歲以下,居住在臺北市/縣六個月以 上，281 名經由年齡（同-5 歲年齡組）、 性別、居住地區配對之社區對照，將 所收集之檢體利用白血球去氧核糖核 酸以聚合酵素連鎖反應為基礎的限制 片段長度多形性(PCR-RFLP)進行 DNA 修復基因hMLH1 、LIG1 之多形性測定。綜合以結構式問卷進行標準化訪 視所蒐集可能致癌之危險因子，以非 條件式對數複回歸分析進行模型建構，做多變項分析，在調整性別、年 齡、抽煙、種族及教育狀況，結果發 現hMLH1 基因多形性與鼻咽癌發生 的危險有顯著相關，LIG1 的基因多形 性與鼻咽癌發生的危險並無顯著相 關。 我們進一步分別以抗EBV 抗體 （anti-EBV antibodies ）、木頭粉塵及甲 醛（formaldehyde ）的職業曝露及亞硝 月安（nitrosamine ）的飲食攝取和抽煙曝 露做分層分析。結果顯示鼻咽癌危險 性在甲醛、粉塵暴露0-10 年之下和 hMLH1 的多形性有顯著相關(表二)， 而在和LIG1 的多形性間則不具顯著性 相關。Genetic polymorphisms of DNA repair genes have been reported to determine susceptibility to several cancers. This study focused on effects of genetic polymorphisms of DNA repair genes hMLH1 and LIG1 interacted with environmental factor on the development of nasopharyngeal carcinoma (NPC). The incidence of nasopharyngeal carcinoma in Chinese is the highest in the world. It is 20-30 times compared to Caucasian, and also much more than Japanese and Korean. Compared to other cancers, the peak of nasopharyngeal carcinoma more frequently occurs in younger age and dominant in male. The impact of the disease especially can not be ignored. The specific aim of this study is to explore the risk factors of nasopharyngeal carcinoma (NPC). A case-control study for NPC which was collaborated with College of Medicine, College of Public Health National Taiwan University and the National Institute of Health in America was conducted in Taiwan from July 1991 to December 1994 to investigate the interaction of environmental carcinogen and genotype polymorphism to the risk of NPC. We enrolled 335 histologically confirmed incident NPC cases who were younger than 75 years old, and had resided in Taipei city/county for at least 6 months, from National Taiwan University Hospital and Mackay Memorial Hospital. Totally 281 healthy community controls were selected by individual matching for sex, age and residence. The study will use the real-time polymerase chain reaction (RTPCR) to analyze the geno types of DNA repair genes hMLH1 and LIG1. Information of Risk factors were obtained through personal interview with structured questionnaire, in which included demographic factors, the history of smoking, drinking, dietary habit, family history of cancer etc. The information were combined with genotyping results to evaluate the effect of NPC development. Unconditional logistic regression was performed to clarify the relationship between various risk factors, genetic susceptibility and NPC occurrence, and also to elucidate their interaction. After adjusting age, sex, ethnicity, educational level, and duration of smoking, NPC is significantly associated with genetic polymorphisms of hMLH1 ，while LIG1 is not. We further stratified by anti-EBV antibodies, occupational exposure to wood dust and formaldehyde, and dietary nitrosamine intake. When stratified 0-10 years exposure to either formaldehyde or wood dust, NPC risk is significantly correlated with hMLH1 polymorphism, while remained no significant association between NPC risk and LIG1.application/pdf45345 bytesapplication/pdfzh-TW國立臺灣大學公共衛生學院流行病學研究所鼻咽癌病例對照研究危險因子DNA 修補基 因基因多形性易感受 性hMLH1LIG1nasopharyngeal carcinomacase-control studyrisk factorDNA repair genesgenetic polymorphismsusceptibility[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/4702/1/922320B002168.pdf