Methylation of the oestrogen receptor gene in non-neoplastic epithelium as a marker of colorectal neoplasia risk in longstanding and extensive ulcerative colitis
Methylation of the oestrogen receptor gene in non-neoplastic epithelium as a marker of colorectal neoplasia risk in longstanding and extensive ulcerative colitis
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DOI：
10.1136/gut.2004.062059
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发表时间：
2005-09-01
期刊：
影响因子：
24.5
通讯作者：
Fujimori, T
中科院分区：
文献类型：
--
作者：
Fujii, S;Tominaga, K;Fujimori, T
背景资料：结肠镜检查被广泛推荐用于长期和广泛的溃疡性结肠炎（UC）患者，以便在早期发现结直肠肿瘤。然而，监测性结肠镜检查是否能有效地早期发现UC相关肿瘤仍存在疑问。非常需要敏感的标记物来识别肿瘤形成风险增加的个体。雌激素受体（OR）基因在结直肠上皮中表现出与年龄相关的甲基化，并且在散发性结直肠肿瘤中频繁甲基化，提示OR甲基化可能易患结直肠肿瘤。目的：阐明分析非肿瘤上皮中OR基因的甲基化是否有助于预测UC患者肿瘤风险增加。材料和方法：共165个非肿瘤性结直肠上皮细胞从30例长期和广泛的UC，包括13例UC患者与肿瘤和17例患者，进行了评价。甲基化特异性聚合酶链反应进行，以确定甲基化状态的OR基因。结果：54 70（77.1%）的非肿瘤性结直肠上皮细胞在UC与肿瘤，但只有23 95（24.2%）没有肿瘤。OR基因的甲基化在UC伴瘤变的非瘤变上皮中的频率显著高于UC不伴瘤变的慢性结肠炎上皮。此外，在UC与肿瘤，OR基因广泛甲基化在整个结肠直肠的非肿瘤上皮细胞相比，在UC没有neoplasia.Conclusion：这些结果表明，OR基因甲基化的分析可能有潜力作为一个有用的标志物，用于识别个体在长期和广泛的UC之间的肿瘤风险增加。
Background: Surveillance colonoscopy is widely recommended in patients with longstanding and extensive ulcerative colitis (UC) in order to detect colorectal neoplasia at an early stage. However, it still remains questionable whether surveillance colonoscopy effectively enables early detection of UC associated neoplasia. There is a great need for sensitive markers to identify individuals at increased risk of neoplasia. The oestrogen receptor ( OR) gene shows age related methylation in the colorectal epithelium and is methylated frequently in sporadic colorectal neoplasia, suggesting that OR methylation may predispose to colorectal neoplasia.Aim: To clarify whether analysis of methylation of the OR gene in non-neoplastic epithelium can contribute to prediction of increased neoplasia risk in UC patients.Materials and methods: A total of 165 non-neoplastic colorectal epithelia from 30 patients with longstanding and extensive UC, including 13 UC patients with neoplasia and 17 patients without, were evaluated. Methylation specific polymerase chain reaction was performed to determine the methylation status of the OR gene.Results: Methylation of the OR gene was detected in 54 of 70 (77.1%) non-neoplastic colorectal epithelia in UC with neoplasia but in only 23 of 95 (24.2%) without neoplasia. Methylation of the OR gene was significantly more frequent in non-neoplastic epithelium from UC with neoplasia than in chronic colitic epithelium from UC without neoplasia. Furthermore, in UC with neoplasia, the OR gene was extensively methylated in non-neoplastic epithelia throughout the colorectum compared with those in UC without neoplasia.Conclusion: These results suggest that analysis of OR gene methylation may have potential as a useful marker for identifying individuals at increased risk of neoplasia among those with longstanding and extensive UC.