For the first time, research has demonstrated the link between diet-related chemicals in the gut and aggressive prostate cancer, suggesting dietary changes may lower risk. Although additional research is required, the study’s principal author asserts that conclusions from the team’s examination of over 700 individuals may have therapeutic ramifications for identifying and averting deadly prostate cancer.
Nima Sharifi, M.D., the study’s principal author, believes findings from the team’s examination of over 700 individuals may have clinical significance for identifying and treating fatal prostate cancer, though additional research is required. According to research, men are more likely to have aggressive prostate cancer if they have greater amounts of certain chemicals associated to nutrition.
Sharifi, director of the Genitourinary Malignancies Research Center at Cleveland Clinic. As we carry out more study in this area, we hope that one day these molecules will serve as early prostate cancer biomarkers and assist in identifying people whose disease risk can be reduced by dietary and lifestyle modifications.
Dr. Sharifi and his associates, Eric Klein, M.D., and Stanley Hazen, M.D., Ph.D., conducted this study. — examined patient data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial of the National Cancer Institute.
Prior to receiving a prostate cancer diagnosis, researchers looked at the baseline levels of specific dietary components and metabolites (byproducts created when a substance is broken down in the stomach) in patients’ blood serum.
Patients in good health and those who later acquired a prostate cancer diagnosis and succumbed to the condition had their blood levels compared.
Men with increased levels of the metabolite phenylacetylglutamine (PAGln) were around two to three times more likely to be diagnosed with fatal prostate cancer, the researchers discovered. Phenylalanine, an amino acid present in several plant- and animal-based protein sources including meat, beans, and soy, is broken down by gut microorganisms to form this metabolite.
In addition to PAGln, researchers also found a relationship between greater levels of two nutrients called choline and betaine with an increased risk for aggressive prostate cancer. These nutrients are plentiful in animal sources including red meat, egg yolks, and high-fat dairy products.
This is the first clinical study of gut microbiome metabolites in connection to prostate cancer outcomes, despite the fact that these nutrients and gut metabolites have previously been investigated in heart disease and stroke.
The connection between PAGln and a higher risk of cardiovascular disease was initially discovered by Dr. Hazen. In 2020, Cell published the findings. Dr. Hazen, director of the Cleveland Clinic Center for Microbiome & Human Health and chair of the Lerner Research Institute’s Department of Cardiovascular & Metabolic Sciences, said: “Interestingly, we found that PAGln binds to the same receptors as beta blockers, which are drugs commonly prescribed to help lower blood pressure and subsequently risk of cardiac events.” This implies that inhibiting the action of the metabolite may account for some of the powerful effectiveness of beta blockers.
Dr. Sharifi is a staff physician in the Department of Cancer Biology at Lerner Research Institute. “New insights are emerging from large-scale clinical datasets that reveal usage of beta blockers is also related with decreased mortality due to prostate cancer,” she added. In order to find novel treatment targets for our patients, “we will continue to collaborate to research the potential pathways relating PAGln activity and prostate cancer disease processes.”
The investigation team will also keep looking into the validity of choline, betaine, and PAGln as biomarkers of aggressive prostate cancer, as well as how dietary treatments might be utilised to control their levels and lower patients’ chance of developing the illness in the future.
The study’s co-first authors are Bryan Naelitz, a current urology resident who was once a medical student in Dr. Sharifi’s lab, and Chad Reichard, M.D., a urologic oncologist at Urology of Indiana and a former urology trainee at Cleveland Clinic. Dr. Klein is a urologist and the former chair of Cleveland Clinic’s Glickman Urological & Kidney Institute. The National Cancer Institute, the National Heart, Lung, and Blood Institute, the Prostate Cancer Foundation, and other National Institutes of Health entities provided funding for the study.
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