Prediction of high carcinogenic state by the analysis of genetic changes in the normal mucosa

通过分析正常粘膜的遗传变化预测高致癌状态

• 批准号: 14571223
• 负责人: KONISHI Fumio
• 金额: $ 2.18万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571223/
• 关键词: Colorectal Cancer; Normal Mucosa; Genetic change; Loss of Imprinting; IGF-II

Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) is one of epigenetic alternations that is thought to be associated with high risk of colorectal cancer. However, there is limited evidence to support a correlation between LOI and colorectal tumorigenesis. From 259 patients with colorectal cancer we investigated 123 informative cases, and in this group the LOI of IGF2 was examined and the results were correlated with clinicopathological characteristics and with the status of the biosatellite instability (MSI). The normal mucosa of LOI positive tumor cases showed significantly higher frequency of naving LOI positivily than that of LOI negative tumor cases (P<0.001). LOI of IGF2 was significantly frequent in the carcinomas of the right colon than in those of the left colon (P=0.044). There were no other significant differences in the factors analyzed between LOI positive and negative tumors. There was no difference in the percentage of LOI positive cases between MSI positive and negative cases. This is the first report on LOI in which a large number of cases were analyzed in detail. The significantly positive result of LOI of IGF2 in the mucosa of LOI positive cancer bearing cases was concordant with the results of the previous report, and suggested the possibility of a role of LOI of IGF2 in the tumorigenesis of the colon and rectum, especially the proximal colon. In contrast to the previous reports, there was no relation between LOI and MSI.

胰岛素样生长因子2(IGF2)的印迹丢失(LOI)是表观遗传学改变之一，被认为与结直肠癌的高风险有关。然而，有有限的证据支持LOI和结直肠肿瘤发生之间的相关性。在259例结直肠癌患者中，我们调查了123例信息性病例，在这组病例中检测了IGF2的LOI，结果与临床病理特征和生物卫星不稳定性(MSI)状态相关。正常黏膜组织中LOI阳性组的频率明显高于LOI阴性组(P&lt；0.001)。右半结肠癌中IGF2基因的LOI显著高于左半结肠癌(P=0.044)。在LOI阳性和阴性肿瘤之间，所分析的因素没有其他显著差异。MSI阳性与阴性病例LOI阳性百分率差异无统计学意义。这是第一份对大量病例进行详细分析的LOI报告。在LOI阳性的癌组织中，IGF2的LOI与文献报道的结果一致，提示IGF2的LOI可能在结肠和直肠，尤其是近端结肠的发生发展中起一定作用。与以前的报道相反，LOI与MSI之间没有关系。

项目成果

小西文雄: "大腸癌とマイクロサテライト不安定性"日本消化器病学会雑誌. 99. 1050-1056 (2002)

Fumio Konishi：“结肠癌和微卫星不稳定”日本胃肠病学会杂志 99. 1050-1056 (2002)。

小西文雄, 河村裕: "テキスト大腸癌"炎症性腸疾患と癌. 2(253) (2002)

Fumio Konishi、Yutaka Kawamura：“文本结直肠癌”炎症性肠病和癌症 2(253) (2002)。

小西文雄, 河村裕: "テキスト大腸癌(炎症性腸疾患と癌)"日本メディカルセンター. 6/253 (2002)

Fumio Konishi、Yutaka Kawamura：“文本结直肠癌（炎症性肠病和癌症）”日本医疗中心 6/253 (2002)。

Shitoh K, Konishi F: "Microsatellite instability as a marker in predicting metachronous multiple colorectal carcinomas after surgery"Dis Colon Rectum. 45. 329-333 (2002)

Shitoh K、Konishi F：“微卫星不稳定性作为预测手术后异时性多发性结直肠癌的标志物”Dis Colon rectum。

甲斐敏弘, 小西文雄: "APC遺伝子"TECHNICAL TERM 消化管. 18-19 (2002)

Toshihiro Kai、Fumio Konishi：“APC 基因”技术术语胃肠道 18-19 (2002)