Zhao Yan, Oki Eiji, Ando Koji, Morita Masaru, Kakeji Yoshihiro, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Cancer Genet Cytogenet. 2010 Jan 15;196(2):133-9. doi: 10.1016/j.cancergencyto.2009.09.009.
The purpose of this study was to evaluate the genetic background of colorectal cancer according to the tumor site, and to investigate the impact of the genetic features regarding the lesion location of colorectal cancer. Microsatellite instability (MSI), DNA index, and the mutation and loss of heterozygosity of the TP53 gene were systemically examined in 180 Japanese colorectal cancer cases. The correlation between these genetic features and clinicopathologic factors was analyzed. A logistic regression was undertaken to analyze the association between genetic features and tumor locations. The data demonstrated location-related genetic differences in colorectal cancer. The proximal subset was distinct in patterns of genomic instability and TP53 gene defects. The genetic features of distal colon cancers paralleled those of rectal cancers. Intriguingly, a multivariate analysis implicated MSI as the only factor significantly associated with tumor location. When MSI tumors were excluded, the statistical association between tumor location and alternations in the DNA index and TP53 vanished. The location-related differences of colorectal cancer were derived from the unequal distribution of the MSI tumors. On the other hand, the microsatellite stable colorectal cancers were genetically homogeneous regardless of the tumor location. Therefore, instead of tumor location, microsatellite status should be a major focus for the study of colorectal cancers in the future.
本研究旨在根据肿瘤部位评估结直肠癌的遗传背景，并探讨结直肠癌病变位置相关遗传特征的影响。对180例日本结直肠癌病例系统检测了微卫星不稳定性（MSI）、DNA指数以及TP53基因的突变和杂合性缺失。分析了这些遗传特征与临床病理因素之间的相关性。采用逻辑回归分析遗传特征与肿瘤位置之间的关联。数据表明结直肠癌存在与位置相关的遗传差异。近端亚组在基因组不稳定性模式和TP53基因缺陷方面有所不同。远端结肠癌的遗传特征与直肠癌相似。有趣的是，多变量分析表明MSI是与肿瘤位置显著相关的唯一因素。排除MSI肿瘤后，肿瘤位置与DNA指数和TP53改变之间的统计学关联消失。结直肠癌与位置相关的差异源于MSI肿瘤的分布不均。另一方面，微卫星稳定的结直肠癌无论肿瘤位置如何，在遗传上都是同质的。因此，未来结直肠癌研究的主要重点应是微卫星状态而非肿瘤位置。
