AORTIC 2011, Cairo, Egypt 30 November–2 December 2011
Combating malaria and Burkitt lymphoma in the EMBLEM study
Dr Sam Mbulaiteye – National Cancer Institute, Bethesda, MD, USA
At this meeting I’ll be talking about Burkitt’s lymphoma, specifically I’ll be talking about the EMBLEM study which is a study we designed to look at questions that were asked fifty years ago when Burkitt’s lymphoma was discovered when malaria was hypothesised as a causal factor in Burkitt’s lymphoma. But definite studies could not be done to show the link, mostly because malaria is repetitive and it’s very difficult to quantify how much malaria somebody has had. What we’re doing in EMBLEM is a case control study where we get cases that have Burkitt’s lymphoma and controls who are children who don’t have Burkitt’s lymphoma and then we are using a genomic approach because some people who have certain genotypes that protect them from malaria will have a lower burden of malaria in their lifetime. So it will actually measure the relationship between malaria and Burkitt’s lymphoma using this indirect approach.
How is the study structured?
That’s an interesting question. Three studies were done in the past looking at this question and those studies were very small. One was 100 cases and 100 controls; one was 36 and one was 95. So for the EMBLEM study we are looking at 1,500 cases and 3,000 controls and because cancer is a relatively rare disease our study is being done in three countries – Uganda, Kenya and Tanzania and in these countries we have gone to regions where malaria transmission is extremely high. In some of the areas where we are doing this study, it’s estimated that up to five infectious mosquitos might bite a child every day, so it’s very intense malaria exposure that we think all children who live in these areas are heavily exposed. The ones who have genetic resistance to malaria will have a slightly lower burden of malaria and those who have no resistance will have a higher burden. So we’ll be able to test our hypothesis that children who have genetic resistance to malaria will have a lower risk for Burkitt’s lymphoma.
What have the results been so far?
Our study is in the early stages; our research is in Africa, as you know, Africa has many other compelling problems – infectious diseases, diarrhoea, respiratory tract infections. So we’ve come along slowly to introduce cancer as an area of interest for public health. Right now we are one year into the accrual, we’ve got some initial data but we do expect to have most of the data within about four years and then we’ll tell you whether the hypothesis is supported.
What has been very interesting about our study is that we’ve introduced some services that were not in the areas where we’re working. These include diagnosing cancer, especially Burkitt’s lymphoma, so there has been an improvement in that area, we can tell you the number that we’ve diagnosed. We’ve improved treatment of Burkitt’s lymphoma, so provided protocol based treatments to the children who attend the hospitals which are participating with us and we are introducing what we call BL, Burkitt’s lymphoma, community awareness campaigns. These are simple, plain language posters that we can use to educate the community and health workers about Burkitt’s lymphoma. So those are the changes that we’ve introduced in the community. We think that in four or five years’ time we’ll have some results to share.
What is the future of the study when more data is collected?
A little bit of history about Burkitt’s lymphoma would be appropriate here. In terms of diseases that we’ve discovered in the last fifty years, Burkitt’s lymphoma was discovered in 1958, it has had a tremendous impact on science. For example, it’s the first cancer where a human virus was found to be associated with cancer. Study of tumour cells revealed genetic abnormalities which we call chromosomal translocations. Manipulation of tumour cells resulted in improvements of growth of human cells. So the study of Burkitt’s lymphoma actually gave birth to many new fields – viral oncology, molecular biology of tumours. So we think that our study is going to do two things, one is it’s going to provide us direct evidence on the link between malaria and Burkitt’s lymphoma but it’s also going to allow us to ask other questions, like about other infections that might be influencing the relations between malaria and Burkitt’s lymphoma. We’re going to be able to use the genomic methods that have come of age now to look for other genetic variants that might influence Burkitt’s lymphoma through non-malaria related mechanisms. So we think we’re going to have a definite result as well as spin-offs that will make this a very interesting study.
From another angle, we could also say that we are re-introducing African populations that are remote back into the scientific enterprise. And I think enquiring, asking what diseases occur there, what genetic risk factors might occur there, would be useful for public health in those areas but it would also be useful for science generally. And we are training the new generation of researchers in Africa.