Kang Sokbom, Kim Yong Beom, Kim Moon-Hong, Yoon Kyung-Sik, Kim Jae Weon, Park Noh Hyun, Song Yong Sang, Kang Daehee, Yoo Keun-Young, Kang Soon Beom, Lee Hyo Pyo
Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, 110-744, South Korea.
Cancer Lett. 2005 Jan 10;217(1):11-6. doi: 10.1016/j.canlet.2004.06.053.
Cyclooxygenase-2 (COX-2) expression is mediated by constitutive nuclear factor (NF)-kappaB. The aim of this study was to investigate the association between the germline alteration of the NF-kappaB binding site of COX-2 and the risk of developing various types of human cancers. Using PCR and DNA sequence analysis, we performed a hospital-based case-control study involving various types of human cancers, namely cervical, breast, lung, and bladder cancer. The COX-2 gene was sequenced in 217 Korean individuals (122 cancer patients; 95 non-cancer patients). We identified 2 novel polymorphisms -1166 C-->G and -1186 T-->G, in the NF-kappaB binding promoter region of COX-2. A polymorphism in nucleotide 1186 was found to be associated with an increased risk of bladder cancer (P=0.038). However, in the case of the other cancers, no significant association was found between polymorphisms in the COX-2 promoter region and the risk of cancer. In conclusion, our results suggest that polymorphisms in nucleotide -1186, which is in the NF-kappaB binding promoter region of the COX-2 gene, may be associated with an increased risk of bladder cancer. Further research is needed to investigate the functional implications of the polymorphisms of the COX-2 promoter gene in human cancer.
环氧化酶-2（COX-2）的表达由组成型核因子（NF）-κB介导。本研究的目的是调查COX-2的NF-κB结合位点的种系改变与发生各种类型人类癌症风险之间的关联。我们采用聚合酶链反应（PCR）和DNA序列分析，开展了一项基于医院的病例对照研究，涉及各种类型的人类癌症，即宫颈癌、乳腺癌、肺癌和膀胱癌。对217名韩国人（122例癌症患者；95例非癌症患者）的COX-2基因进行了测序。我们在COX-2的NF-κB结合启动子区域鉴定出2种新的多态性——-1166 C→G和-1186 T→G。发现核苷酸1186处的多态性与膀胱癌风险增加相关（P = 0.038）。然而，对于其他癌症，未发现COX-2启动子区域的多态性与癌症风险之间存在显著关联。总之，我们的结果表明，COX-2基因的NF-κB结合启动子区域中核苷酸-1186处的多态性可能与膀胱癌风险增加相关。需要进一步研究来调查COX-2启动子基因多态性在人类癌症中的功能意义。
