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2021 Michael and Lori Milken-PCF Young Investigator Award

Improving the Utility of Polygenic Risk Scores and Rare Genetic Variants for the Prediction of Prostate Cancer in Men from Diverse Populations

Burcu Darst, PhD
Fred Hutchinson Cancer Research Center

Mentors: Christopher Haiman, ScD, David Conti, PhD

Description:

  • Prostate cancer represents one of the largest health disparities in the US, with men of African ancestry having the highest incidence and mortality rates.
  • Prostate cancer is one of the most heritable types of cancer. Differences in germline genetics likely contribute in part to prostate cancer disparities.
  • A multi-ancestry polygenic risk score (PRS) has recently been developed that is highly predictive of prostate cancer risk across diverse populations. However, clinical implementation of the PRS first requires a better understanding of how best to use and interpret it in different populations.
  • Dr. Burcu Darst is studying how to improve the PRS and incorporate rare genetic variants in different ancestry populations, in order to further improve the ability to identify men who would benefit from earlier or more frequent prostate cancer screening.
  • In this project, Dr. Darst will use genetic data from over 100,000 men from over 75 distinct populations, to optimize use and interpretation of the multi-ancestry PRS in men from diverse and admixed populations.
  • In addition, the combined effect of rare, high-penetrant variants and PRS on prostate cancer risk in men from diverse populations will be quantified.
  • If successful, this project will substantially improve the ability of the PRS to appropriately identify men who would benefit from earlier or more intensive prostate cancer screening across diverse populations, particularly African ancestry men.

What this means to patients: Prostate cancer is highly heritable and the ability to identify men at highest genetic risk will greatly improve individualized prostate cancer screening strategies and reduce disparities. Dr. Darst will determine how to optimally use a multi-ancestry polygenic risk score (PRS) in combination with rare genetic variants, in different ancestral populations, ultimately reducing prostate cancer mortality rates and prostate cancer disparities.