Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients
Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients
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DOI：
10.1093/carcin/bgh304
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发表时间：
2005-01-01
期刊：
影响因子：
4.7
通讯作者：
Nakachi, K
中科院分区：
文献类型：
--
作者：
Yuasa, Y;Nagasaki, H;Nakachi, K
通过DNA甲基化的表观遗传基因沉默是肿瘤发生机制的重要步骤之一，包括胃中的肿瘤。癌症患者过去的生活方式因素，如蔬菜的摄入量，在影响胃癌发生方面非常重要。然而，DNA甲基化与癌症患者过去饮食习惯之间的关系在很大程度上仍然未知。CDX 2同源框转录因子在肠发育中起关键作用，但CDX 2也在大多数肠上皮化生和部分胃癌中表达。我们用甲基化特异性PCR（MSP）分析了胃癌细胞系中CDX 2 5' CpG岛的甲基化状态，然后发现甲基化阳性细胞经5-氮杂-2'-脱氧胞苷处理后CDX 2 mRNA被激活。我们进一步通过MSP检测了原发性胃癌中CDX 2的甲基化状态，并将其与患者过去的生活方式（包括饮食习惯）进行了比较。在58例男性患者中有20例（34.5%）和15例女性患者中有1例（6.7%）发现CDX 2甲基化。由于女性患者的甲基化频率较低，因此仅对男性病例进行分析。CDX 2甲基化与绿色茶和十字花科蔬菜摄入量减少有关，也与饱食或暴饮暴食习惯有关。这些发现与胃癌的流行病学观察结果一致。我们还分析了p16/INK 4a和hMLH 1的甲基化状态，但它们的频率与饮食因素或其他生活方式因素无关。因此，饮食可能是决定基因（如CDX 2）甲基化状态以及由此产生的致癌基因异常表达的重要因素。
Epigenetic gene silencing through DNA methylation is one of the important steps in the mechanism underlying tumorigenesis, including in the stomach. Past lifestyle factors of cancer patients, such as intake of vegetables, are very important in affecting gastric carcinogenesis. However, the relationship between DNA methylation and past dietary habits in cancer patients remains largely unknown. The CDX2 homeobox transcription factor plays a key role in intestinal development, but CDX2 is also expressed in most of the intestinal metaplasia and part of the carcinomas of the stomach. We analyzed the methylation status of the CDX2 5' CpG island in gastric cancer cell lines by methylation-specific PCR (MSP), and then CDX2 mRNA was found to be activated after 5-aza-2'-deoxycytidine treatment of the methylation-positive cells. We further examined the methylation status of CDX2 in primary gastric carcinomas by MSP and compared it with the past lifestyle of the patients, including dietary habits. Methylation of CDX2 was found in 20 (34.5%) of the 58 male patients and one (6.7%) of the 15 female patients. Since the methylation frequency was low in the female patients, the analysis was performed only on the male cases. CDX2 methylation was correlated with the decreased intake of green tea and cruciferous vegetables, and also with full or overeating habits. These findings are consistent with epidemiological observations on gastric cancer. We also analyzed the methylation status of p16/INK4a and hMLH1, but their frequencies were not associated with dietary factors or other lifestyle factors. Thus, diet could be an important factor determining the methylation status of genes such as CDX2 and the resultant aberrant expression of genes involved in carcinogenesis.