Hereditary non-polyposis colorectal cancer is predicted to contribute towards colorectal cancer in young South African blacks

L Cronjé,M Ramsay,P.J Becker,A.C Paterson

doi:10.4102/sajs.v105i1/2.5

Abstract

A disproportionately large number of young ( 50 years), those from young black patients presented more often with a low methylation phenotype (CIMP-L) and high levels of microsatellite instability (MSI-H). Furthermore, as determined by real-time PCR using probe technology, the tissues from 35% of young blacks showed mutations within exon 1 of the KRAS gene. The BRAF-V600E mutation was only evident in the case of a single young black patient. Based on these results it seems likely that a proportion of CRC cases in young black patients from South Africa develop through the accumulation of mutations resulting in a mismatch repair deficiency linked to MSI-H and, possibly, germline mutations in the mismatch repair genes. The features in these patients are consistent with a diagnosis of the Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome. This finding has important implications for patient management and suggests that family members may be at high risk for CRC. : colorectal neoplasms, hereditary cancer syndromes

Highlights

Colorectal carcinogenesis involves the stepwise accumulation of mutations and/or epigenetic alterations, leading to the transformation of normal colonic epithelia
The familial form of this pathway is the autosomal dominantly inherited predisposition to familial adenomatous polyposis (FAP) that is initiated by germline mutations in the adenomatous polyposis coli (APC) gene, and characterised by the presence of adenomatous polyps which develop into colorectal cancer if left untreated.[3]
This study investigated the specific molecular features associated with colorectal cancer (CRC) in a group of South African patients

Summary

Introduction

Colorectal carcinogenesis involves the stepwise accumulation of mutations and/or epigenetic alterations, leading to the transformation of normal colonic epithelia. This process may develop and progress over a period of 10 to 15 years. Comprehensive studies have examined both morphological and molecular changes associated with the initiation and progression of colorectal cancer. The classical pathway, somewhat involved in all of the pathways described, involves the somatic mutational inactivation of the adenomatous polyposis coli (APC) gene in colorectal epithelial cells.[1] This leads to a cascade of events including, amongst others, degradation of β-catenin binding sites and interference with E-cadherin homeostasis during tumour initiation, and to p53 gene mutations during tumour progression.[2] The familial form of this pathway is the autosomal dominantly inherited predisposition to familial adenomatous polyposis (FAP) that is initiated by germline mutations in the APC gene, and characterised by the presence of adenomatous polyps which develop into colorectal cancer if left untreated.[3]

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