To view the original video and read the News Release, please go to http://www.nichd.nih.gov/news/releases/Pages/111610-prostate-cancer-genes.aspx
NICHD logoNational Institutes of HealthEunice Kennedy ShriverNational Institute of Child Health & Human Development
Study: Key Enzyme Gene Variations Linked to Prostrate Cancer
Constantine Stratakis, M.D., D.Sc.Director, Division of Intramural ResearchEunice Kennedy Shriver National Institute of Child Health and Human Development
Dr. Stratakis on camera
Dr. Constantine Stratakis: This study is a study of patients that have developed prostate cancer. And what we did study was their DNA and the DNA of their tumors. And we specifically looked for genetic defects of a gene called phosphodiesterase 11A, or PDE11A. And we sequenced the gene and the DNA of the patients, derived from their blood samples—and the DNA from their tumors—derived from their tumor samples. And we compared the frequency of genetic alterations in that gene in these patients and their tumors with the DNA from controls.
Dr. Stratakis: The study was conducted here at the [Eunice Kennedy Shriver] National Institute of Child Health and Human Development in an Intramural Laboratory, but the samples were collected in Brazil. Doctor Fabio Faucz, a post-doctoral fellow from Brazil, was doing research in our laboratory here at the NICHD and had collected the samples from these patients himself and from a group of investigators in Brazil.
Dr. Stratakis: What we found out was that the patients had in their blood DNA, and of course as a consequence in their tumor DNA, a higher frequency of genetic alterations in phosphodiesterase 11A when compared to normal controls.
Dr. Stratakis: So, for men with prostate cancer, approximately 30 percent were carriers of one or the other of these eight variations, whereas these variations were only found in about 10 percent of the normal controls.
Dr. Stratakis: The activity of the enzyme appears to be decreased when these genetic alterations are present. And when this is happening there appears to be an increased risk for developing these tumors. Now, the increased risk of course is indirectly derived from our data because we don’t show in any way that when we actually decrease the activity of the enzyme we get a cell becoming cancerous. We’re not showing that. We’re not saying that. What we’re saying is that when you have this genetic alteration the activity of the enzyme is decreased—partially decreased—not completely inactivated, partially decreased. And when you have that, and you have that in your endocrine cells, there appears to be an increased frequency of tumors.
Dr. Stratakis: So there are no known medications that are specifically targeting phosphodiesterase 11A. But phosphodiesterase 11A is a member of a large family of enzymes that are called phosphodiesterases and some of them are targets of medications that have been used for many years in medicine for heart disease, for lung disease, and most recently for erectile dysfunction. Some of these medications that are targeting members of the phosphodiesterase family for treating heart disease, lung disease, or erectile dysfunction do in fact inhibit phosphodiesterase 11A at the doses that they are administered for the treatment of these other disorders. So, the inhibition of phosphodiesterase 11A in the context of the use of these medications is a side effect in essence. But of course we do know today that at the doses that these medications are being used, there is inhibition of the enzyme.
Dr. Stratakis: The takeaway message for the general public is that phosphodiesterase 11A is yet another enzyme that has sufficiently large genetic viability to allow for certain things, certain diseases, certain pathologies to be associated more frequently with one versus the other form of the enzyme. And, that lots of studies need to be done to try to tackle those—get the answers to these associations—and, of course, use them in a way that would be beneficial to our patients and to perhaps treating the diseases that are associated with these particular glands and enzyme.
Dr. Constantine Stratakis: Another take-home message here is that phosphodiesterase 11A may be one of the hundreds or maybe even thousands of genes that will be used in the future to determine each one of our profiles for the risk of certain diseases. In this particular case, obviously, it could be the profile for the risk for prostate cancer. But we have already talked about PDE11A in adrenal tumors and PDE11A in testicular tumors so it could be used in the testing for the profile of a number of tumors. And, as I said, it’s just one of hundreds of other genes—maybe thousands of genes—that we will be studying in the future for what we call individualized medicine.
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