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Research Projects

Identifying Genetic Markers of Susceptibility to African Oesophageal Cancer

Identifying Genetic Markers of Susceptibility to African Oesophageal Cancer

Prof Christopher Mathew

Prof Christopher Mathew

Prof Christopher Mathew

Title of the project

Identifying genetic markers of susceptibility to African Oesophageal Cancer.

Project Description

Oesophageal squamous cell carcinoma (OSCC) is common in Black populations of sub-Saharan Africa, with high incidence regions in East and South Africa. Clinical presentation in Africa is late, and treatment is mainly palliative with a very poor prognosis. Various environmental risk factors have been identified, but the possible contribution of genetics to disease risk is an important question which is unresolved. The main purpose of this project is to test the hypothesis that genetic variation in the South African Black population contributes significantly to the risk of this type of cancer. This will be done by testing genetic risk factors for OSCC which have been identified in other populations for association with OSCC in the South African Black population, and by carrying out fine-scale genetic mapping in positive regions of the genome to identify causal genes and variants. We also seek to confirm preliminary evidence of several novel associations of OSCC which we detected in Black cases and controls from the Cape Province. This will be done by testing an initial panel of 96 genetic variants for association with OSCC in 1000 cases and 800 non-cancer controls from the Johannesburg Cancer Study. We will also use the data to test for gene/environmental interactions, and to build a model for risk prediction by combining genetic and environmental risk factors for OSCC.

Non-scientific report:

The aim of our project is to find out whether variation in the genetic code of human genomes contributes to the high incidence of oesophageal squamous cell cancer (OSCC) in sub-Saharan Africa, and particularly in South Africa. Large studies have been carried out in other parts of the world with a high incidence of this form of cancer, especially in China. This has led to the discovery of genetic variants (i.e. changes in the genetic code) in some genes which increase the risk of OSCC, so our first aim is to test these genes and variants in our local African populations to see whether they also increase risk of OSCC here.

The reason for wanting to find such genes and variants is two-fold. One is that the identity of the genes would give us a window into the molecular pathways that underlie the development of these cancers, and this knowledge may help us to develop new and better treatments for this cancer, which currently has a dismal prognosis. The second reason is that if we can identify genetic profiles that confer a high risk of OSCC, we could investigate the potential use of these profiles in screening middle-age African people for OSCC before they show symptoms of this cancer. This could result in a large improvement in survival and cure rates for this form of cancer.

In our first year of the grant, we have genotyped 25 genetic variants in DNA samples from nearly 1000 OSCC cases and 1000 non-cancer controls to look for association with OSCC. Our work so far suggests that most of the genetic variants associated with OSCC in other populations are not associated in our local African populations. So either the genes which are important for OSCC are different in Africa, or the actual genetic variants are different and we will have to carry out more detailed studies of these genes to find the relevant variants. We have, however, found variants in two genes which are associated with OSCC in our population. One of these genes is called CHEK2, which has been found to be associated with several different cancers in other populations. The other is a gene called c5orf30, about which very little is known. We plan to follow up these findings by investigating these genes in more detail, and to see whether these genetic associations are connected to lifestyle factors such as smoking and alcohol use.


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