Research Continues on Genetics of Prostate Cancer

Effort aims to find cause and treatments for prostate cancer

Dr. Constantine Stratakis

Prostate cancer is the second-most common cancer among men in the United States after skin cancer, with 233,000 new cases projected for this year.

The leading risk factors for prostate cancer are age, race, and a family history of the disease. Prostate cancer is rarely seen in men younger than 40, but the incidence rises significantly each decade after that. The risk of developing and dying from prostate cancer is higher among black men than whites. And experts believe that 5–10% of prostate cancer cases are caused primarily by the inheritance of high-risk genes. Men who have one or more close relatives with prostate cancer are at increased risk.

To learn more about research on the disease, we spoke with Constantine Stratakis, M.D., D.Med.Sc., Director of the NICHD's Division of Intramural Research, who has found variations in a gene (PDE11A) that appear to increase prostate cancer risk. The genetic variations impair the enzyme phosphodiesterase 11A, which is involved in cell energy metabolism and helps regulate cells' responses to hormones and other signals.

Previous studies by NIH researchers have linked genetic variations in PDE11A with increased susceptibility to testicular cancer and adrenal tumors.

The following is a brief Q&A with Dr. Stratakis about his work on the genetics of prostate cancer. You can also find a video in which Dr. Stratakis discusses his work on PDE11A.

Your areas of expertise are developmental endocrinology and genetics, and much of your work has focused on the adrenal gland. How did you become interested in prostate cancer?
You directed a study that looked at variations of the gene PDE11A among men with prostate cancer. What did you find?
What is the significance of these findings for men's health care? For example, could it affect future screening or treatment methods?
African American men are more at risk for prostate cancer, and prostate cancer can run in families. Could the genetic variations you found be related to the higher risk in these populations?
Is it possible for men to find out whether they have these genetic variations? If they could, would it be useful information to have?
Have you continued with this line of research? If so, what are you doing now?
If a friend asked you about prostate cancer, what would be your most important message?

  1. Your areas of expertise are developmental endocrinology and genetics, and much of your work has focused on the adrenal gland. How did you become interested in prostate cancer?

    We found that the same genetic defects that predisposed a person to adrenal gland tumors could be implicated in the predisposition to prostate cancer.
  2. You directed a study that looked at variations of the gene PDE11A among men with prostate cancer. What did you find?

    We found that certain genetic variants of PDE11A occurred more frequently in men with prostate cancer. PDE11A was also inactivated in the tumor tissue of men who were carriers of these defects. Based on the function of the gene, we think that its inactivation in prostate tissue allows for the proliferation of prostate cells, which is the hallmark of cancer.
  3. What is the significance of these findings for men's health care? For example, could it affect future screening or treatment methods?

    It is hard to say what this will lead to because we are at the very beginning of understanding PDE11A's involvement in this process. Clearly, it is possible that PDE11A will one day be part of a genetic screen that will better identify who is more likely to get prostate cancer or who is not.

    In terms of possible treatments, medications that affect the molecular pathways controlled by PDE11A may be developed and used in conjunction with other drugs against the cancer.
  4. African American men are more at risk for prostate cancer, and prostate cancer can run in families. Could the genetic variations you found be related to the higher risk in these populations?

    It could be, but our study did not address genetic risk differences among different populations.
  5. Is it possible for men to find out whether they have these genetic variations? If they could, would it be useful information to have?

    Sequencing a person's DNA is rapidly becoming routine, part of the daily clinical practice, especially in the field of cancer. So, the answer is that PDE11A genetic variants may be identified through this process. Sometimes, variants are only present in tumor DNA. Tumor DNA sequencing is now used extensively to guide clinical decision making in cancer treatments.
  6. Have you continued with this line of research? If so, what are you doing now?

    We are continuing to investigate PDE11A's involvement in tumor formation in animal models. We are also studying humans with various PDE11A defects and adrenal gland tumors to understand more about the function of the gene.
  7. If a friend asked you about prostate cancer, what would be your most important message?

    Like most cancers, prostate cancer is a complicated disease. We now understand more about how it develops and what sustains it, but most treatments for advanced cancer are not very successful. Early detection is by far the most effective way of making sure that cancer does not advance. Genetic tests that identify predisposing factors, such as PDE11A and many other genetic variants, which have been recently identified, are promising tools in the early detection of this disease, and they hold promise for the development of better drugs to fight the disease.

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Originally Posted: June 26, 2014

 

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