Department of Terry Fox Cancer Research Lab, China Medical University Hospital, Taichung, Taiwan, ROC.
Oral Oncol. 2009 Sep;45(9):789-93. doi: 10.1016/j.oraloncology.2008.12.002. Epub 2009 Feb 13.
The DNA double strand break repair gene Ku80 is thought to play a major role in the caretaking of the overall genome stability. It is very possible that defective in double strand break repair capacity can lead to human carcinogenesis. Thus, the polymorphic variants of Ku80 were firstly investigated regarding their association with oral cancer susceptibility. In this hospital-based case-control study, the association of Ku80 promoter G-1401T (rs828907), promoter C-319T (rs11685387), and intron19 (rs9288518) polymorphisms with oral cancer risk in a Taiwanese population was investigated. 600 patients with oral cancer and 600 age- and gender-matched healthy controls recruited were genotyped and analyzed by PCR-RFLP method. There were significant differences between oral cancer and control groups in the distributions of their genotypes (P=0.0038) and allelic frequencies (P=0.0044) in the Ku80 promoter G-1401T polymorphism. In the other two polymorphisms, there was no difference between both groups in the distribution of either genotype or allelic frequency. There is a synergistic gene-environmental interaction between Ku80 and areca chewing. Compared with G/G genotype in Ku80 promoter G-1401T, the G/T plus T/T significantly enhanced the risk only in the areca chewers (odds ratio=1.603; 95% confidence interval=1.053-2.011), not in the non-areca chewers. In conclusion, the Ku80 promoter G-1401T is correlated with oral cancer susceptibility and this polymorphism may be a useful marker for oral cancer prevention and early detection.
Ku80 是 DNA 双链断裂修复基因，被认为在维持基因组稳定性方面发挥着重要作用。双链断裂修复能力缺陷很可能导致人类致癌。因此，首先研究了 Ku80 启动子 G-1401T(rs828907)、启动子 C-319T(rs11685387)和内含子 19(rs9288518)多态性与口腔癌易感性的关系。本病例对照研究中，采用 PCR-RFLP 方法对台湾人群 Ku80 启动子 G-1401T(rs828907)、启动子 C-319T(rs11685387)和内含子 19(rs9288518)多态性与口腔癌易感性的关系进行了研究。共纳入 600 例口腔癌患者和 600 例年龄和性别匹配的健康对照者，采用 PCR-RFLP 法进行基因分型和分析。结果显示，口腔癌组和对照组 Ku80 启动子 G-1401T 多态性的基因型分布（P=0.0038）和等位基因频率（P=0.0044）差异有统计学意义。另外两个多态性位点在两组间基因型或等位基因频率分布无差异。Ku80 与咀嚼槟榔之间存在协同的基因-环境相互作用。与 Ku80 启动子 G-1401T 的 G/G 基因型相比，G/T 加 T/T 基因型仅在咀嚼槟榔者中显著增加风险（比值比=1.603；95%置信区间=1.053-2.011），而非咀嚼槟榔者中无此相关性。结论：Ku80 启动子 G-1401T 与口腔癌易感性相关，该多态性可能是口腔癌预防和早期检测的有用标志物。
