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.