Obesity link to the spread of prostate cancer made clearer in new genetic research

There’s already been plenty of research suggesting that obesity is linked to advanced prostate cancer, but very little evidence to suggest exactly what the link between fats and prostate cancer spread could be. But in new research published this week, scientists in Boston think they may have found such a connection in the makeup of our genes.

Humans have two copies of all their genes, and sometimes one copy can get deleted or damaged. In the new study, the researchers were investigating two genes, PTEN and PML, whose job it is to prevent tumors from spreading. They experimented with deleting both of them together in mice (who also have these genes) to find out more about what triggers prostate cancer to spread.

They knew that 70 per cent of men with localised prostate cancer had lost one copy of the PTEN gene, and losing both copies of the gene is closely linked with the spread of tumours to other parts of the body. But they also knew that deleting PTEN in mice with localised prostate cancer did not have the same effect, and the cancer stayed in the prostate.

The effects of removing PML and PTEN genes in mice

So in their first experiment, the researchers looked at what happened if they deleted PML as well as PTEN from mice with localised prostate cancer. Their theory was based on studies of human cancers that found both copies of PML present in most localised prostate cancers, but neither in a third of aggressive cancers and both PTEN and PML missing in a fifth of advanced cancers.

Sure enough, they found removing PML from the PTEN-free mice was enough to spur the cancer on to leave the prostate and spread to other parts of the body. However, they were extremely surprised – and interested – to find the mice massively increased the amount of fat they produced.

This led the researchers to ask whether this increase in fat production could be what was really driving the prostate cancer to spread. And if so, by blocking it, could the tumours shrink?

Luckily, there is already a fat-blocking drug called (appropriately) fatostatin, which is currently in clinical trials for obesity. So the researchers gave this drug to the mice missing both PTEN and PML genes and found that this did indeed inhibit both tumour growth and spread.

Now the scientists turned their attention to diet and whether a high-fat Western diet had the same effect on the prostate cancer spreading as deleting PML. So they switched the PTEN-free mice's usual low-fat, vegan diet for one high in fat that would increase their fat production. The result? The cancer did spread beyond the now obese mice's prostates.

What does this mean for men, rather than mice?

We can’t say yet how applicable this research will be to humans, although the researchers did find enriched fat production machinery in advanced human prostate cancers. But this is the first time there's been a proven biological link between fat production and cancer metastasis, and shows how both genes and diet can play a part in driving and controlling the disease.

"The models of prostate cancer being explored by this study are helping us to develop a picture of how genetics and obesity work together to affect a man’s risk of developing aggressive forms of the disease," says our director of research, Dr Iain Frame.

"In the long term, this knowledge may help us make more effective predictions about which men’s prostate cancers are likely to spread, and potentially also help develop new treatments to prevent this from happening in the first place."

For now, our advice remains the same whether you’re a man with prostate cancer or not: a healthy lifestyle and a balanced diet are only ever going to be good for you.