在台灣，嚼食檳榔已被確認為引起口腔癌前病變的最主要危險因子，檳榔的組成成分會導致DNA損傷。X射線修復交叉互補組1（XRCC1）基因，在DNA修復過程中扮演著關鍵性的角色，XRCC1基因多形性可能會影響DNA修復能力和口腔癌前病變的易感性。本研究目的在探討XRCC1基因多形性與嚼食檳榔相關的口腔黏膜白斑症及口腔黏膜下纖維化風險的相關性。本實驗總共收錄449位有習慣性嚼食檳榔的男性，其中包括169位罹患口腔黏膜白斑症，82位罹患口腔黏膜纖維化，208位健康對照組）。我們採用聚合&#37238;連鎖反應-限制酵素片段長度多型性和即時聚合&#37238;連鎖反應進行基因型測定。結果發現 : XRCC1 –77 C對偶基因及T/C+C/C基因型與降低口腔黏膜白斑症的風險顯著相關，其校正勝算比分別為0.54（95%信賴空間為0.34-0.85）及0.47（95%信賴空間為0.28-0.78）。XRCC1 399 Gln對偶基因和399 Arg/Gln+Gln/Gln基因型與增加口腔黏膜白斑症及口腔黏膜下纖維化風險具顯著意義的相關，對口腔黏膜白斑症而言，其校正勝算比分別為1.94（95%信賴空間為1.41-2.67）及2.64（95%信賴空間為1.73-4.03），而口腔黏膜下纖維化的校正勝算比分別為1.67 （95％信賴空間為1.11-2.49）以及2.30 （95％信賴空間為1.35-3.91）。於單套型或雙套型分析時發現，危險對偶基因（-77T或399Gln）數愈少者，則罹患口腔黏膜白斑症（兩者 Ptrend<0.001）及口腔黏膜下纖維化（Ptrend=0.056 及 Ptrend=0.040）的風險愈低並具線性趨勢。結論 ： XRCC1 -77和399基因多形性可能與口腔癌前病變風險相關。

Betel quid（BQ）chewing is recognized as a major risk factor for oral precancerous lesions（OPLs）in Taiwan. The compositions of Betel quid could cause DNA damage. X-ray repair cross complementing Group 1（XRCC1）plays a crucial role in the process of DNA repair. Polymorphisms in XRCC1 gene may affect DNA repairing ability and modulate the susceptibility of OPLs. The aim of this study was to investigate the association of XRCC1 genetic variants with the risk of BQ-related oral precancerous lesions, including oral leukoplakia（OL） and oral submucous fibrosis ( OSF ). A total of 449 males（169 OL cases, 82 OSF cases, and 208 healthy controls）who habitually chewed BQ were recruited. The genotypes were determined by PCR-RFLP and TaqMan real-time assays. The C allele and T/C+C/C genotypes at XRCC1 -77 were associated with the reduced risk of OL ( AOR=0.54, 95%CI:0.34-0.85 and AOR=0.47, 95%CI:0.28-0.78, respectively ). The 399Gln allele and 399 Arg/Gln+Gln/Gln genotypes were associated with the increased risk of OL（AOR=1.94; 95%CI: 1.41-2.67 and AOR=2.64; 95%CI: 1.73-4.03, respectively）and OSF ( AOR=1.67; 95%CI: 1.11-2.49 and AOR=2.30; 95%CI: 1.35-3.91, respectively ). The haplotypes or diplotypes contain fewer risk alleles（-77T or 399Gln） were with lower risk of OL（both Ptrend<0.001）and OSF (Ptrend=0.056 and Ptrend=0.040, respectively). In conclusion, our results suggest that polymorphisms of XRCC1 at -77 and 399 may be associated with the risk of OPLs.

摘要 Ⅶ
Abstract Ⅸ
壹、前言 1
一、口腔癌及口腔癌前病變 1
1. 口腔黏膜白斑症 2
2. 口腔黏膜下纖維化 4
二、口腔癌前病變之流行病學 6
三、菸、酒、檳榔與DNA的損傷及口腔癌前病變病因及
病理學 8
四、DNA損傷修復 10
五、鹼基刪除修復（BER ） 11
1. X射線修復交叉互補組1（XRCC 1） 13
2. XRCC1 基因多形性與口腔癌及口腔癌前病變之風險 15
(1) UTR-77T>C（rs3213235）基因多形性 15
(2) XRCC1Arg194Trp（rs1799782）基因多形性 16
(3) XRCC1 Arg 280 His （rs25489）基因多形性 16
(4) XRCC1 Arg399Gln （rs25487）基因多形性 17
六、研究目的 19
貳、材料方法 20
ㄧ、研究族群 20
二、血液檢體收集及處理 21
三、DNA萃取及基因型定型檢測（Genotyping assay） 21
四、統計分析 23
參、結果 25
一、 人口學特徵 25
二、 單核&#33527;酸多形性（SNPs）與口腔癌前病變之風險 26
三、 單套型基因（Haplotypes）及雙套型基因（diplotypes）
與口腔癌前病變之風險分析 31
肆、討論與結論 38
伍、圖表 45
陸、參考文獻 63
柒、附錄 76

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