A group of researchers from Cleveland Clinic have recently shown that aggressive prostate cancer is linked to diet-associated molecules in the gut microbiome. The findings, published in Cancer Epidemiology, Biomarkers & Prevention, are noted as the first of their kind (2021; doi: 10.1158/1055-9965.EPI-21-0766). The research also found that two nutrients found in common animal products like red meat and high-fat products were also linked to lethal prostate cancer.
"There was no evidence of this specific connection prior to this study," said Nima Sharifi, MD, Director of the Center for GU Malignancies Research at the Lerner Research Institute. "There is certainly a lot of evidence out there that there is an association between diets and risk of developing prostate cancer in various population-based studies. But there hasn't been much evidence linking diet to how aggressive the cancer is."
Given that prostate cancer is a pretty heterogeneous disease, it's really a fraction of it that ends up turning into lethal prostate cancer-so the researchers aimed to find a connection between diet and lethal prostate cancer.
"Some of them get diagnosed and don't need much treatment, but others are much more aggressive and can lead to death," Sharifi noted. "So we were interested in identifying not just the link with risk of developing prostate cancer, but also the risk of lethal prostate cancer. We wanted to take advantage of an opportunity to look at not just what people ate, but to see if we can measure something in the blood that is indicative of what nutrients they consumed, as well as things that are reflective of what the gut microbiome does to those dietary nutrients."
Something already known is that there is data to link certain animal-derived nutrients and risk of prostate cancer. But something not known before this study is that diet is linked to how lethal prostate cancer can be. According to the research, men with elevated levels of the metabolite phenylatectylglutamine (PAGln) were 2 or 3 times more likely to get a lethal diagnosis of prostate cancer.
"There's more recent data just out last year that [PAGln] is linked to cardiovascular disease," said Sharifi. "It looks like it works through adrenergic receptors. And we also generally know that things that put you at cardiovascular risk also seem to be linked to cancer risk. So given that recent development, we were specifically motivated to look for that in this study. I think finding the link between PAGln and risk for lethal cancer was totally new and pretty surprising."
The study also suggests that there may be a defensive element in beta-blockers, as PAGln binds to the same receptors as the drug used to treat high blood pressure.
"There is population-based data for a potential protective effect of beta-blockers for prostate cancer," said Sharifi. However, "our study is also an association, so we can't through the nature of the study establish a mechanistic link. It is certainly suggestive. I think with this association, as well as the association with PAGln, we should have separate studies done to see if beta-blockade as an intervention or doing something like changing PAGln levels or changing diet can modify that risk."
Sharifi noted that getting these answers is a daunting challenge because the natural history of prostate cancer is typically very long, and the next studies done will also be lengthy.
"We were fortunate in that we didn't do this study in men who already have a diagnosis. We obtained blood prior to diagnosis. A lot of these are around 20 years old, so it took a long time for that study to mature and be able to put this together. So to study this prospectively along with any other interventions will probably take just as long. It's a long road ahead."
While the researchers knew about the association between meat and animal products and the risk of prostate cancer, Sharifi said it's more complicated. "Our data also suggests that it's not always a direct link, that the gut microbiome clearly plays a role, and that those interactions can be pretty complex. So what links certain nutrients in food to lethal prostate cancer-it may not be what you expect and we need to figure out how this occurs and to stop it from happening.
"While we must wait patiently for these future studies to be done, we now know there is this correlation and that diet will be crucial in prevention moving forward," he noted. "I think this tells us that, while there is a genetic component to it, there are also lifestyle factors that can affect the risk of developing lethal prostate cancer. This adds to the body of evidence for the latter part and it adds to the evidence that there are things that can be done in terms of diet that may suppress the risk of developing lethal prostate cancer."
Dillon Stickle is a contributing writer.