| 摘要: | 計畫中文摘要 一般咸信，除?煙、酒、檳榔之外，維繫整個基因體的DNA 修補系統?發生缺陷， 也極可能與口腔癌化有關。因此，對於DNA 修補系統基因之全面性探討，將有助於瞭 解整個口腔癌化的機轉。煙、酒、檳榔等??所產生的效應將導致包括DNA 雙股斷? 等損傷。雙股DNA 斷??無法即時的修補將嚴重地造成基因體的?穩定，因此，少許 DNA 雙股斷?修補上的差?性就可能與口腔癌化有關。我們的研究已發現，在DNA 雙股斷?“非同源末梢黏合DNA 修補 (NHEJ)”中的XRCC4 基因，其多型性與口腔癌 的?患?有明顯的關?性。基於此重要的發現，我們將分別從人?族群、細胞模式及 動物模式等層次，?探討“NHEJ 在口腔癌化過程中所扮演的角色?。我們的設計上亦 同時兼顧?基因型與表現型的交互配合，可以?具有系統性與完整性。 第一?將針對NHEJ 之基因進?單核?酸多型性的鑑定，同時，基因與基因間的交 互作用，以及環境因子與基因遺傳因子對於口腔癌的共同效應，?將一併進?分析。 第二?將使用口腔癌細胞株針對各型NHEJ 能?等表現型進?探究。第三?將?用藥 物誘發口腔癌小鼠模式，?進?癌化過程的?續性探究。此計劃將有助於基因與基因 間、基因與環境間、及NHEJ 在口腔癌化過程中所扮演的角色之瞭解，並提供口腔癌 基因治?之嶄新方向。
Oral cancer is ranked the forth leading cause of cancer incidence among Taiwanese male population. Until now, the overall mechanism(s) behind the development of oral cancer remains unrevealed. It is believed that in addition to environmental factors, such as smoking, alcohol drinking, and betel quid chewing, the subtle deficiencies of DNA repair systems, caretakers care of the genome, maybe also related to oral carcinogenesis. Therefore, the systematic understanding of the genotypes and the phenotypes of these DNA repair genes will help us to reveal the oral carcinogenesis progression. The direct or indirect intracellular effects of exposures to smoking, alcohol drinking, and betel quid chewing can cause DNA damages, including double strand breaks. A loss or delay in repairing these double strand breaks on time may cause a dramatically instable of the genome. Thus, a subtle variation in the capacity of double strand break repair may be related to oral carcinogenesis. Recently, we have indeed found that the genetic polymorphic variations of XRCC4, a member of the important system for DNA double strand break repair, non-homologous end-joining (NHEJ), are associated with oral cancer susceptibility. Thus in this 3-year project, we aim to elucidate the contribution of NHEJ to oral carcinogenesis via three levels including human population, cell model, and animal model, respectively. An overall genotype-phenotype study will be conducted. In the first year, we will genotype the variant single nucleotide polymorphisms in some NHEJ genes, and evaluated the associations between these polymorphisms and oral cancer risk. By the way, the effects of gene-gene interactions, and the environmental factors will be combined with these genetic factors to evaluate their combined contribution to oral cancer etiology. |
