A correlation was found between the variation in the extent and level of MSI and the age of onset of carcinoma, suggesting differences in the rate of tumour progression. A high frequency of MSI in hyperplasias, found only in MSH2 mutation carriers, might indicate a more rapid tumour progression, correlating with an earlier age of onset of carcinoma. The present study indicates that assessment of altered protein staining combined with MSI analysis of endometrial tumours might direct the mutational analysis of MMR genes. Ltd. Different mechanisms in the tumorigenesis of proximal and distal colon cancers. Environment or genetic constitutions can lead to an increase of genetic or epigenetic events and increase the risk for malignancy.
Genomic instability is seen in most types of malignancies.
Almost all sporadic MIN tumors occur in the proximal colon, whereas most sporadic CIN tumors are distributed in the distal colon. The two familial syndromes, familial adenomatous polyposis and Lynch syndrome, constitute models for the different carcinogenic mechanisms in CIN and MIN tumors, respectively. This article reviews the principal differences between CIN and MIN tumors, evidence for a proximal and distal route in carcinogenesis, gender differences, and aspects of methylation in CIN and MIN colorectal tumorigenesis. The genetic basis of this disease has been linked to mutations in genes associated with DNA mismatch repair. A large proportion of families harbor changes in one of two genes, hMSH2 and hMLH1.