Yuasa Yasuhito, Nagasaki Hiromi, Akiyama Yoshimitsu, Hashimoto Yutaka, Takizawa Touichirou, Kojima Kazuyuki, Kawano Tatsuyuki, Sugihara Kenichi, Imai Kazue, Nakachi Kei
Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo, Japan.
Int J Cancer. 2009 Jun 1;124(11):2677-82. doi: 10.1002/ijc.24231.
Epigenetic silencing of genes by aberrant DNA methylation is recognized as a crucial component of the mechanism underlying tumorigenesis. However, the relationship between DNA methylation and the past lifestyle in cancer patients remains largely unknown. We examined the methylation statuses of 6 tumor-related genes, CDX2 (homeobox transcription factor), BMP-2 (bone morphogenetic protein 2), p16 (INK4A), CACNA2D3 (calcium channel-related), GATA-5 (transcription factor) and ER (estrogen receptor), in 106 primary gastric carcinomas by methylation-specific PCR and compared them with the past lifestyles of the patients. The methylation frequencies of the genes were 23.6, 21.7, 9.4, 32.4, 40.8 and 59.1%, respectively. Significant association was found between a decreased intake of green tea and methylation of CDX2 and BMP-2. More physical activity was correlated with a lower methylation frequency of CACNA2D3. Of these 6 genes, the methylation statuses of CDX2, BMP-2 and p16 revealed a significant interrelationship and those of CACNA2D3, GATA-5 and ER did likewise. Thus, some epidemiological factors, such as green tea intake, could be important as to determination of the methylation statuses of selected genes and may influence the development of cancer, including that of the stomach.
异常DNA甲基化导致的基因表观遗传沉默被认为是肿瘤发生机制的关键组成部分。然而，癌症患者DNA甲基化与过去生活方式之间的关系仍 largely unknown。我们通过甲基化特异性PCR检测了106例原发性胃癌中6个肿瘤相关基因CDX2（同源框转录因子）、BMP-2（骨形态发生蛋白2）、p16（INK4A）、CACNA2D3（钙通道相关）、GATA-5（转录因子）和ER（雌激素受体）的甲基化状态，并将其与患者过去的生活方式进行比较。这些基因的甲基化频率分别为23.6%、21.7%、9.4%、32.4%、40.8%和59.1%。发现绿茶摄入量减少与CDX2和BMP-2的甲基化之间存在显著关联。更多的体育活动与CACNA2D3较低的甲基化频率相关。在这6个基因中，CDX2、BMP-2和p16的甲基化状态显示出显著的相互关系，CACNA2D3、GATA-5和ER的甲基化状态也是如此。因此，一些流行病学因素，如绿茶摄入量，对于确定特定基因的甲基化状态可能很重要，并可能影响包括胃癌在内的癌症发展。
