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The analysis of the role of loss of genomic imprinting in gastro-intestinal carcinogenesis

基因组印记缺失在胃肠道癌发生中的作用分析

基本信息

批准号：
11470259
负责人：
IKEGUCHI Masahide
金额：
$ 6.72万
依托单位：
TOTTORI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470259/
关键词：
genomic imprinting loss of imprinting insulin-like growth factor 2 gastric cancer colorectal cancer family aggregation of GC multifocal occurrence of GC ゲノムインプリンティング IGF-2 ロスオブインプリンティング家族性癌

项目摘要

Genomic imprinting is the phenomenon by which the two alleles of certain genes are differentially expressed according to their parental origin. This phenomenon is essential to normal organ development. Recently, the loss of imprinting (LOI) of some genes has been reported to correlate with the occurrence of some human hereditary diseases or to correlate with tumorigenesis. In gastro-intestinal cancers, the existence of family aggregation of cancers is well known. In the present study, the role of LOI in gastro-intestinal carcinogenesis, especially in occurrence of family aggregation of cancers was investigated. In gastric cancer, we found that a family history of gastric cancer seemed to be a risk factor of development of gastric cancer. Further, a family history of gastric cancer was found to be associated with multifocal occurrence of gastric cancer. In colorectal cancer, the LOI of the insulin-like growth factor 2 (IGF2) gene was detected in 22 %, while the LOI of H19 gene was not detected. This finding indicates that in colorectal carcinogenesis, the LOI of IGF2 gene may play an important role but the LOI of H19 may not. Moreover, the LOI of IGF2 gene in peripheral blood leukocytes was detected in 10 % of 262 normal Japanese volunteers. We are now following these 262 healthy volunteers. If the incidence of development of colorectal cancer is higher in IGF2-LOI-positive group than in IGF2-LOI-negative group, the LOI of IGF2 gene may occur not only epigenetically but also genetically and the LOI of IGF2 gene may be a fundamental gene abnormality in colorectal carcinogenesis. Moreover, it will be possible to identify the high risk group of development colorectal cancer by checking the LOI of IGF2 gene in peripheral blood.

基因组印记是某些基因的两个等位基因根据其亲本起源差异表达的现象。这种现象对于正常器官发育至关重要。最近，据报道，一些基因的印记丢失（LOI）与一些人类遗传性疾病的发生或与肿瘤发生相关。在胃肠道癌症中，癌症家族聚集的存在是众所周知的。本研究探讨了LOI在胃肠道癌发生中的作用，特别是在癌症家族聚集性发生中的作用。在胃癌方面，我们发现胃癌家族史似乎是胃癌发生的危险因素。此外，发现胃癌家族史与胃癌的多灶性发生有关。在结直肠癌中，胰岛素样生长因子2（IGF2）基因的LOI检出率为22%，而H19基因的LOI未检出。这一发现表明，在结直肠癌发生过程中，IGF2基因的LOI可能发挥重要作用，而H19基因的LOI则可能不起重要作用。此外，在262名正常日本志愿者中，10%的人外周血白细胞中IGF2基因的LOI被检测到。我们现在正在追踪这 262 名健康志愿者。如果IGF2-LOI阳性组的结直肠癌发生率高于IGF2-LOI阴性组，则IGF2基因的LOI不仅可能在表观遗传上发生，而且可能在遗传上发生，IGF2基因的LOI可能是结直肠癌发生的基本基因异常。此外，通过检测外周血中IGF2基因的LOI，还可以确定罹患结直肠癌的高危人群。