The need for African-specific genotyping platforms to understand the genetic susceptibility to oesophageal cancer in South African populations

Cancer is seen as a growing health problem in Africa, with incidences and deaths expected to increase by 70% by 2030 (1). This is due to both the anticipated increase in population size and the expected increase in life-expectancy resulting from a reduction in death rates from other diseases (2). Another important factor is the changing lifestyle habits of populations in the region, with increased tobacco use, excessive alcohol consumption and a rise in obesity caused by an unhealthy diet and lack of physical activity (3).

Oesophageal cancer is the ninth most common form of cancer in Africa, with higher incidence rates in Eastern and Southern Africa (1). As with other low- and middle-income countries (LMICs), the predominant form of oesophageal cancer in the region is oesophageal squamous cell carcinoma (OSCC), in contrast to adenocarcinoma in high-income countries (HICs). Particularly high incidence rates have been observed in the Eastern Cape Province (former Transkei region), where oesophageal cancer is the most common form of cancer in males (23.2 cases per 100,000 population) and the second most common in females (14.5 cases per 100,000) (4). Encouragingly, incidence rates have declined by 30% between 2003-2007 and 2008-2012, however the reasons for this reduction are not yet known (4).

The cause of the high incidence rates in these regions of South Africa is still not fully understood but possible risk factors include alcohol and tobacco use, nutritional deficiencies, consumption of maize contaminated with the Fusarium fungus, and human papilloma infection (HPV) (5).

Genetic risk factors may also play a role in OSCC development. In Chinese populations, with a high incidence of OSCC, genome-wide association studies (GWAS) have identified over 10 loci associated with the disease (6-9). However, these associations have not been replicated in South African Black populations (10). One possible reason for this is that genotyping platforms used in these GWAS were designed for European/Asian populations which are not as genetically diverse as African populations. Hence, if the variants genotyped by the chosen genotyping platform, are neither the causal variant nor able to “tag” the causal variant by being in linkage disequilibrium with it, then the strength of the association signal may be lower in African populations.

At present, no GWAS have been performed to determine the genetic cause of OSCC in South African populations, primarily due to the need for large sample sizes to perform well-powered studies and a lack of funding. Ideally, future GWAS would be carried out using an African-specific genotyping platform to enable more genetic loci to be investigated. It will be interesting to see whether there are common genetic risk factors between the high risk regions found in South African populations and those in China, or whether these are in fact distinct.

In general, research into diseases in LMICs, especially cancer, is lagging compared to HICs but initiatives such as Human Heredity and Health in Africa (H3Africa), which is investigating the genomics and environmental determinants of common disease in African populations, are important developments to not only study the causes of diseases to improve the health of African populations but to create and expand collaborative world-class research throughout the continent.

References

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