Hereditary Non-Polyposis Colorectal Cancer is Predicted to Contribute towards Colorectal Cancer in Young South African Blacks

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 from35of 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 Cancer in South Africa: a Heritable Cause Suspected in many Young Black Patients

Background. Colorectal carcinoma (CRC) has a low incidence among the black African population. Largely unrecognised in the scientific literature is the fact that a disproportionately large number of young black patients (50 years old) present with CRC. Objectives. To analyse those tumours; which we propose may link them to morphological features associated with known genetic pathways. Methods. A retrospective review of South African patients histologically diagnosed as having CRC by the Division of Anatomical Pathology; National Health Laboratory Service (NHLS) and the University of the Witwatersrand (1 732 patients from 1990 to 2003). The histology was fully reviewed in 609 patients (1997 - 2002); and all specimens from patients 50 years of age were subjected to immunohistochemistry tests for mismatch repair proteins; as well as APC and p53 proteins. Results. Most young patients (50 years) were black (41v. 10white; p=0.001). Blacks had predominantly proximal tumours and significantly more poorly differentiated and/or mucinous tumours (p=0.006); and loss of mismatch repair protein expression was more evident than in whites. Conclusions. It seems likely that CRC in young blacks develops through the accumulation of mutations; most probably via mis- match repair deficiency or promoter methylation; which in turn is linked to poor differentia- tion and a mucinous architecture