Molecular Causes of Early-onset Colorectal Cancers in South Africans of African Ancestry: The CRC-Gen Study
Dr June Fabian
Dr June Fabian
- Director of the Wits Donald Gordon Medical Research Institute (WDGMRI); Faculty of Health Sciences, University of the Witwatersrand
Project Title
Molecular causes of early-onset colorectal cancers in South Africans of African ancestry: The CRC-Gen Study
Project Description
Early-onset colorectal cancer (EOCRC), diagnosed before age 50, disproportionately affects people of African ancestry. It tends to be more aggressive, diagnosed at later stages, and associated with poorer outcomes, particularly in low- and middle-income countries. Despite this, most global research has focused on populations of European ancestry, leaving a critical gap in understanding hereditary and somatic drivers in African populations.
The CRC-Gen Study addresses four key questions:
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To what extent do germline variants contribute to EOCRC in South Africans of African ancestry?
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What are the main somatic drivers of tumour development?
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How do somatic mutation profiles and mutational signatures differ from those in European populations, and what are the clinical implications?
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How can genomic data be aligned with national reporting frameworks and integrated with patient and public involvement (PPI) to inform cancer policy and advocacy?
To answer these questions, the study will:
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Retrospectively analyse 100 tumour samples from an established colorectal cancer repository using whole-exome sequencing to identify ancestry-associated somatic features.
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Establish a prospective longitudinal cohort of 120 newly diagnosed EOCRC patients for integrated germline–somatic profiling, linked to detailed phenotype and lifestyle data.
Importantly, the prospective component embeds structured PPI and advocacy—the first initiative of its kind in South Africa, where no formal EOCRC advocacy groups currently exist for people of African ancestry.
The CRC-Gen Study will deliver the first comprehensive genomic profile of EOCRC in South Africans of African ancestry, strengthen national reporting platforms (NCR, SANCaPS), build research capacity, and lay the foundation for equitable, patient-centred precision oncology in South Africa.
