| 摘要: | Oral cancer is ranked the forth leading cause of cancer incidence among Taiwanese male population. 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 toelucidate the contribution of NHEJ to oral carcinogenesis via three levels including human population, cell model, and animal model, respectively. In the first year, 2009-2010, we have investigated some important candidate variant single nucleotide polymorphisms in three of 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 have be combined with these genetic factors to evaluate their combined contribution to oral cancer etiology. We have published several SCI papers in journals such as Laryngoscope, Oral Oncology, Anticancer Research, etc.In the current year, more than we have planned, we have established several oral cancer primary cell lines from the oral cancer patients, and to compare them with those normal cells. We are now examining their differences in phenotypes such as in vitro and in vivo NHEJ and overall double strand break repair capacities investigated. By the way, the differential expression patterns between cancer and normal cells of the NHEJ proteins will be examined by Northern and Western Blotting, separately. Also, we have being prepared the animal model for the third year. |
