鄭玉娟2006-07-252018-06-292006-07-252018-06-292001-07-31http://ntur.lib.ntu.edu.tw//handle/246246/4675DNA 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hOGG1 、XRCC1 基因多形性與其他異物代謝基因、環境因 子共同作用時，發生鼻咽癌之關係。 本研究採病例對照研究法，共分析 334 名鼻咽癌病例及283 名經性別、年齡 及居住地區配對之社區對照。萃取研究個 案週邊血液白血球細胞之DNA ，以聚合 連鎖反應為基礎的限制片段長度多形 性（PCR-RFLP ）鑑定基因多形性。 研究結果發現：台灣不同氏族 hOGG1 Cys 326 、XRCC1 His 280 及XRCC1 Gln 399 對偶基因頻率在社區對照組的分布 分別為0.56-0.62 、0.03-0.14 及0.26-0.31 。 經調整性別、年齡、氏族及抽煙習慣後， 攜帶hOGG1 Ser326Cys 或Cys326Cys 基 因型者罹患鼻咽癌的相對危險性為 Ser326Ser 基因型的1.66 （95 ﹪信賴區間： 1.03-2.67 ）倍；攜帶XRCC1 Arg280His 或His280His 基因型者罹患鼻咽癌的相對 危險性為Arg280Arg 基因型的0.66 倍（95 ﹪信賴區間：0.44-0.98 ）。同時攜帶hOGG1 及XRCC1 危險基因時，罹患鼻咽癌的相 對危險性為3.2 倍（95 ﹪信賴區間： 1.1-9.4 ）；加入抽菸量分層分析後，總抽菸 量在25 包-年以上且又攜帶hOGG1 、 XRCC1 危險基因者罹患鼻咽癌的相對危 險性約為8 倍（95 ﹪信賴區間：0.6-97.8 ）； 當hOGG1 、XRCC1 及CYP2E1 危險基因 共同作用時，罹患鼻咽癌的相對危險性可 高達近28 倍（95 ﹪信賴區間：3.8-201.7 ）。 本研究分析結果發現，hOGG1 及 XRCC1 基因多形性與台灣地區鼻咽癌之 發生具相關性；hOGG1 、XRCC1 及 CYP2E1 基因多形性對於台灣地區鼻咽癌 之發生具有強烈的交互作用存在。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 hOGG1 and XRCC1 on the development of nasopharyngeal carcinoma (NPC). We conducted a case-control study to investigate the genotypes of 334 patients with NPC and 283 healthy community controls matched by sex, age and residence. DNA was extracted from mononuclear cells obtained from peripheral blood. The polymerase chain reaction (PCR)-based restriction fragment length polymorphism assay was used to identify the genetic polymorphisms. Each allele frequency of the hOGG1 Cys 326 , XRCC1 His 280 and Gln 399 among different clans in controls was 0.56-0.62, 0.03-0.14 and 0.26-0.31, respectively. After adjustment for sex, age, clan, and smoking habits, the odds ratio of developing NPC for hOGG1 codon 326 genotypes of Ser/Cys and Cys/Cys compared with Ser/Ser genotype was 1.66 (95%CI: 1.03-2.67); for XRCC1 codon 280 genotypes of Arg/His and His/His compared with Arg/Arg genotype was 0.66 (95%CI: 0.44-0.98). Among subjects with putative high risk genotypes of both hOGG1 and XRCC1, the odds ratio of developing NPC was 3.2 (95%CI: 1.1-9.4). Furthermore, subjects with putative high risk genotypes of all hOGG1, XRCC1 and CYP2E1 had an additive risk effect on NPC. The odds ratio of developing NPC was nearly 28-fold (95%CI: 3.81-201.66). The results suggest the polymorphisms of the DNA repair genes including hOGG1 codon326 and XRCC1 codon280 were associated with an increased risk of NPC. There was a synergistic effect for the genetic polymorphisms of hOGG1, XRCC1 and CYP2E1 on the development of NPC; the higher the number of the putative risk genes, the higher the risk of NPC.application/pdf54869 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DNA修補基因hOGG1XRCC1nasopharyngeal carcinomacase-control studyDNA repair genes[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/4675/1/892314B002427.pdf