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Solving a 50-year mystery: how is malaria causing cancer in Africa’s “lymphoma belt?”

Cancer has a variety of different causes.  Genetic mutations can be passed on from our parents, such as the BRCA gene made famous by Angelina Jolie.  DNA damage can be caused by exposure to chemicals, smoking, or the damage caused by the sun.  But a number of cancers can be caused as a result of infections by viruses, bacteria, or even parasites.

Cancer-causing infections

For example, the Epstein-Barr virus (EBV) infects 90% of the world population apparently causing little harm.  But EBV can cause cancers such as lymphomas, carcinomas and childhood cancers.  Dr Dirk Pegtel is studying what goes wrong when a virus infection causes cancer.

Stomach cancer nearly always develops in people who have had a long-term infection with a bacterium called Helicobacter pylori, and Professor Mark Pritchard is trying to find molecules that can help identify people more likely to develop stomach cancer.

And earlier this year we reported on another story, where Worldwide Cancer Research funded scientists pinned down how a dangerous tropical parasite, which is transmitted by ticks, manages to hijack healthy cells and turn them into cancer-like invasive cells.

But in the news today are some exciting results from Research Associate Professor Davide Robbiani, working in the lab of Michel Nussenzweig at The Rockefeller University, who we funded back in 2011.

Dr Robbiani has been trying to find out how the immune system might be playing a role in the development of one of the most frequent cancers among African children called Burkitt’s lymphoma.

In equatorial Africa, a region of the globe known as the “lymphoma belt,” children are ten times more likely than in other parts of the world to develop Burkitt’s lymphoma, a highly aggressive blood cancer that can be fatal if left untreated.  That area is also plagued by high rates of malaria, and scientists have spent the last 50 years trying to understand how the two diseases are connected.

The link has been a mystery: The parasite that causes malaria, infects red blood cells and liver cells, while Burkitt’s lymphoma starts off in infection-fighting white blood cells called B cells. So how could a malaria infection increase a child’s risk of developing this type of cancer?

Working with colleagues at Rockefeller University, their research has finally helped explain why.  Working in mice, they found that the same enzyme that helps create antibodies that fight off the malaria parasite also causes DNA damage that can lead to Burkitt’s lymphoma.  This research is published in the journal Cell.

A ‘necessary risk’

“I think of this process as a ‘necessary risk,’” says Robbiani.  “The body needs this enzyme in order to produce potent antibodies to fight malaria.  But in the process, the enzyme can cause substantial collateral damage to the cells that produce it, and that can lead to lymphoma,” he adds.

Groups at Rockefeller and elsewhere are trying to understand how the enzyme causes this collateral DNA damage, which could lead to new treatments.  “If we could somehow limit this collateral damage to cancer-causing genes without reducing the infection-fighting powers of B cells, that could be very useful,” he says.  “But first, we have to find out how the collateral DNA damage occurs in the first place.”

There are no other cancers associated with malaria, but lymphomas have been linked to other types of infections, and not just in Africa, Robbiani says.  For instance, people with hepatitis C or the ulcer-causing bacterium Helicobacter pylori have a higher incidence of non-Hodgkin lymphomas, he notes.  “It’s possible that this enzyme also plays a role in the association between these other infections and cancer,” Robbiani says.  “This is purely a speculation at this point, though highly suggestive.”

Dr Robbiani told us: "We are very grateful to Worldwide Cancer Research for its decision to support our study that enhance the understanding of how chronic infection promotes the genesis of lymphoma. This was a long and technically challenging study, which we started more than six years ago. At that time governmental agencies were not keen to support it, as the project was deemed too risky."

Unfortunately, this reluctance to fund more innovative research is still present. This is why the Worldwide Cancer Research grant was so important to us, and is so important to many, especially young scientists. We would not have been able to embark on this work without the initial financial push by Worldwide Cancer Research.

Further information

The research was funded by Worldwide Cancer Research, the Fondazione Ettore e Valeria Rossi, and U.S. federal grants.

You can read more about the story on the Rockefeller University Newswire

Photo caption: When a mouse’s immune system reacts to red blood cells infected with the malaria parasite (purple spots within some of the pink cells above), changes occur in the DNA of B cells. These changes, though helpful in protecting from malaria, can sometimes lead to cancer.

Photo credit: Michel Nussenzweig lab at Rockefeller University

Written by Dr Gwen Wathne, Worldwide Cancer Research's Impact Manager

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