Genetic Risk Score Predictive of Aggressive Prostate Cancer Interview with:
“DNA” by Caroline Davis2010 is licensed under CC BY 2.0Tyler Seibert, MD, PhD

Radiation Oncology
Center for Multimodal Imaging & Genetics
UC San Diego What is the background for this study?

Response: Prostate cancer is an extremely common condition in men. Many die from it each year, and many others live with debilitating pain caused by prostate cancer. Screening for prostate cancer with prostate-specific antigen (PSA) testing can be effective, but there are concerns with the test.

  • First, screening everyone gives a large proportion of false-positive results, and those men end up undergoing unnecessary procedures such as prostate biopsy. S
  • econd, a significant portion of men who develop prostate cancer will develop a slow-growing form of the disease that is likely not life-threatening and may not require treatment.

    These concerns have led to a drop in prostate cancer screening. But avoiding screening leaves a large number of men vulnerable to diagnosis of an aggressive prostate cancer at a later stage, when it is more difficult—or impossible—to be cured. Doctors are left to guess which of their patients are at risk of aggressive disease and at which age they need to start screening those patients.

Our study sought to develop a tool to provide men and their doctors with objective, personalized information about each man’s risk of prostate cancer. Based on the man’s genetics, we wanted to predict the risk of aggressive prostate cancer and at what age in his life that risk becomes elevated. What are the main findings?

Response: Using data from tens of thousands of men from Europe, Australia, and the United States, we were able to develop a genetic score (called a polygenic hazard score) based on 54 DNA markers. This score was optimized to predict age of onset of aggressive prostate cancer. We then tested its performance on data from over 6,400 men aged 50-70 years who participated in a PSA screening trial in the United Kingdom. The testing showed remarkably accurate prediction for prostate cancer. The genetic score was also much more useful than asking men whether they had relatives with prostate cancer. What should clinicians and patients take away from your report?

Response: Our report suggests that the genetic score could assess an individual man’s age-specific risk of aggressive prostate cancer. The score could be calculated once for a man while he is still young and provide valuable information for the rest of his life, whether identifying him as someone who could develop the disease in his 40s or reassuring him that his risk is relatively low. What recommendations do you have for future research as a result of this study?

Response: The biggest limitation of the study is reliance on data from men of European ancestry. Our next goal is to obtain enough genetic and clinical data form men of other genetic backgrounds to make sure we have a tool that will work for all men. Thank you for your contribution to the community.


Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts

BMJ 2018; 360
(Published 10 January 2018)
Cite this as: BMJ 2018;360:j5757

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.


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Last Updated on January 29, 2018 by Marie Benz MD FAAD