Why are African and African Caribbean men at higher risk of prostate cancer? Despite promising new research, the reasons are still unclear, as Sophie Lutter explains.

19 Oct 2015

Why are black men at great risk of prostate cancer?

We know that 1 in 4 black men will be diagnosed with prostate cancer in their lifetime compared to 1 in 8 white men. We just don’t know why.

We know that it isn’t about differences in hormone levels, and we can’t use socio-economic factors to explain it either. Could there be a genetic link? Well, there could but we haven’t found it yet. That doesn’t mean that there isn’t one, though, or we’re not looking. It’s just that, so far, it’s been unexpectedly difficult to find.

Last year, we gave a Pilot Award, funded by The Movember Foundation, to Dr Christine Galustian at King’s College London. She wanted to investigate whether there could be a link between African and African Caribbean men producing an altered form of a particular protein, called Duffy Antigen Receptor for Chemokines (DARC), and developing aggressive prostate cancer.

A link to malarial protection?

DARC is usually displayed on the surface of red blood cells and endothelial cells (the cells that make up blood vessel walls). Its job is to deactivate cancer promoting proteins in the blood by grabbing hold of them and pulling them into the cell and out of action.

The problem is that DARC also has a nasty side. The same ‘snatch and grab’ technique that puts cancer-promoting proteins out of action can also make it nice and easy for malaria parasites to use DARC as a secret entrance into red blood cells. So in areas where malaria is traditionally widespread, such as Africa and the Caribbean, some people make DARC differently. It’s their body’s way of protecting them from deadly malaria infections.

Some people produce another form of DARC – version B – that is either displayed as usual on red blood cells and endothelial cells, but binds everything (including malaria parasites) less strongly than the original DARC (version A), so that it isn’t as easily hijacked by the malaria parasites.

Other people express the same weaker ‘B’ form of the DARC protein but don’t display it at all on red blood cells, so completely removing the malaria parasites’ secret entrance to these cells. This is version Y.

Dr Galustian wondered whether this evolutionary protection against malaria could actually be putting [some] men at higher risk of aggressive prostate cancer.

Dr Galustian wondered whether this evolutionary protection against malaria could actually be putting the men who produce versions B and Y at higher risk of aggressive prostate cancer. She wondered whether the fact that these forms of DARC don’t ‘snatch and grab’ malaria parasites as well as version A also meant that they’re less efficient at clearing cancer promoting molecules from the blood stream.

Sounds possible, doesn’t it? In fact, other researchers had already found a link between versions B and Y expression and higher incidence and spread of prostate cancer in African and African Caribbean men.

Problem samples and surprising results

Unfortunately, the path of scientific discovery rarely runs smooth. Firstly, Dr Galustian couldn’t recruit as many black men as she’d hoped to her study, so there were more white men than black men in her final sample list. This isn’t the end of the world, but she still needs a few more black men to take part to be able to wrap up the investigation.

Secondly, most of the men taking part in the study (both black and white) had fairly early stage prostate cancer. Not many men with advanced disease signed up to take part.

Finally, when Dr Galustian looked at the DNA samples from the men taking part in the study to see what type of DARC protein they would display, she spotted some surprising results.

As she expected, most of the white men in the study produced version A, but a few produced version B. However, every single one of the black men in her study produced version Y protein. She doesn’t yet know what this means. It could be to do with the ethnic origins of the men in her study as version Y is more common in African men than African Caribbean men for example. Or it could mean something more significant. It’s too early to tell yet.

Unfortunately, the fact that all the black men produced the same type of DARC, and all the men (black and white) were at a similar stage of prostate cancer, meant that Dr Galustian can’t yet draw any definite conclusions about whether the type of DARC protein black men produce affects their risk of prostate cancer.

Without taking these leaps and exploring these avenues, we’ll never find the answers we’re looking for.

But Dr Galustian hasn’t given up. She is still trying to recruit the last few black men to her trial to see if she can get the numbers she needs to draw some conclusions. She’s also hoping to look in tissue samples from men who’ve had a prostatectomy to see if she can see any differences there between the type of DARC expressed and the grade of cancer. Finally, she might also have a look at DNA samples from men who don’t have prostate cancer, to see whether there are differences between men who do or don’t have prostate cancer and their DARC protein.

Overall, we still don’t know why 1 in 4 black men will get prostate cancer, or why black men are three times more likely to have prostate cancer than a white man of the same age. But even if we don’t end up with a nice neat answer all wrapped up and tied with a pretty bow, research like Dr Galustian’s is a step in the right direction. Without taking these leaps and exploring these avenues, we’ll never find the answers we’re looking for.

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