DNA修補系統在維持遺傳基因完整性是不可或缺的。而DNA修補基因的先天多型性可能與口腔癌易感性的變異有密切關係。我們執行一個以醫院為底的病例對照研究，來探討DNA修補系統相關的五個修補基因(XRCC1, XPA, XPC, hMLH1與XRCC3)其八點基因多型性與口腔鱗狀上皮細胞癌之相關性。自2003年11月到2004年10月於高雄榮民總醫院共完成收集144名新診斷的口腔鱗狀上皮細胞癌病人和215名健康配對，以聚合

DNA repair systems are indispensable for maintaining genomic integrity. Inherited polymorphisms of DNA repair systems related repair genes may contribute to individual variations in genetic susceptibility to oral cancer. We carried out a hospital-based case-control study to investigate the association of eight various polymorphisms in five DNA repair genes (XRCC1, XPA, XPC hMLH1 and XRCC3) with the risk for oral squamous cell carcinoma (OSCC). A total of 144 newly diagnosed OSCC and 215 frequency-matched controls were recruited between November 2003 and October 2004 at Kaohsiung Veterans General Hospital. Genotyping was performed using the PCR-RFLP techniques. In our results, we found that the XPA A23G polymorphism was strongly associated with OSCC risk (p for linear trend, 0.030) especially combined with XPC (p for linear trend, 0.026). Moreover a trend toward increased risk of OSCC was found when with the increasing putative high-risk genotypes of DNA repair genes (p for linear trend, 0.007). Therefore, we suggested that these polymorphisms in five repair genes were associated with the risk of OSCC.
Furthermore, to investigate the prognosis of buccal carcinoma (BC), the most common site of oral cancer in Taiwan, we identified the protein expressions of XRCC1 and XPA and evaluated the relationship between expression level of proteins with clinicopathologic characteristics and survival outcome. A total of 138 primary BC specimens were recruited at KSVGH between 1994 and 2005 and the protein expression levels were identified by use of immunocytochemistry. The overall cumulative 5-years survival rate, 10-years survival rate and 12-years survival rate of BC patients were 66%, 55% and 44%, respectively. Survival curve of BC was significantly correlated with pathological stage, tumor size, lymph node metastasis, tumor differentiation, post-operative RT or CT. However, there were no significant differences between the survival curves of BC patients and the expression levels of XRCC1 and XPA, either in the univariate or the multivariate analysis.
In conclusion, the combined effect of seven polymorphisms in five repair genes was associated with the risk of OSCC. However, the expression levels of XRCC1 and XPA were not associated with the survival for patients with BC.

Chapter 1 General Introduction 1
1.1 Backgrounds and Significance 2
1.2 Specific Aims 19
1.3 References 20
Chapter 2 The Relation of Polymorphisms in DNA Repair Genes to OSCC Risk: A Case-Control Study. 27
2.1 Summary 28
2.2 Introduction 29
2.3 Patients and Methods 36
2.4 Results 41
2.5 Discussion 48
2.6 References 58
Tables 65
Figures and Figure Legends 71
Chapter 3 The Relation of the XRCC1 and XPA Expression Patterns with the Prognosis of Baccal Carcinoma: A Retrospective Cohort Study 75
3.1 Summary 76
3.2 Introduction 78
3.3 Patients and Methods 82
3.4 Results 86
3.5 Discussion 90
3.6 References 94
Tables 97
Figures and Figure Legends 104
Chapter 4 Future Perspectives 111
4.1 Specific Aims 112
4.2 Experimental Designs 114
4.3 References 117

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