Abstract for presentation at 11th International Congress of Human Genetics

Colorectal cancer in young Africans: do they follow the conventional pathway?

  • Leandra Cronje, University of the Witwatersrand and The National Health Laboratory Service, South Africa
  • Prof Michele Ramsay, University of the Witwatersrand and The National Health Laboratory Service, South Africa
  • Prof Alan Paterson, University of the Witwatersrand and The National Health Laboratory Service, South Africa
  • Dr Piet Becker, Biostatistics Unit, Medical Research Council of South Africa, South Africa

    • Amongst African and Caucasian patients a disproportionately large number of young African patients present with colorectal cancer (CRC) in South Africa. We proposed that morphological and molecular analysis of these tumours might link them to the features associated with the “serrated pathway” involving promoter methylation and low levels of microsatellite instability (MSI-L). Retrospectively, we therefore investigated the morphological and molecular features of 45 CRC cases in South Africa, without knowledge of family history. Eighty five percent of young patients (<50 years) were African (p = 0.000), predominantly male (56%; p = 0.026) with proximal tumours (25%; p = 0.064). These patients showed significantly more poorly differentiated tumours (p = 0.001) and extracellular mucin (p = 0.006). Molecular analysis revealed a low methylation phenotype (CIMP-L) and microsatellite instability (MSI-L), with 44% of cases methylated in the MGMT promoter region. Loss of heterozygosity at the APC gene locus was evident in 20% of these cases. On the basis of this study it seems likely that CRC in young African patients develop through the accumulation of mutations through promoter methylation, which in turn is linked to a poor differentiation and a mucinous architecture.

    Conference Organiser - ICMS Pty Ltd