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2022 Henry M. Jackson Foundation for the Advancement of Military Medicine – PCF Young Investigator Award

Genetic Determinants of Aggressive Prostate Cancer in African American Patients

Indu Kohaar, PhD
Center for Prostate Disease Research, Uniformed Services University of the Health Sciences; Henry M. Jackson Foundation for the Advancement of Military Medicine

Mentors: Gyorgy Petrovics, PhD, William Douglas Figg Sr., PharmD

Description:

  • African Americans have 1.7-fold higher incidence, and 2.1-fold higher mortality rates for prostate cancer than Caucasian Americans. Also, African Americans are generally younger at diagnosis, tend to present with more aggressive disease features, and are at a greater risk for metastasis.
  • Inequities in socio-economic status and access to healthcare are large contributors to prostate cancer disparities. However, even after adjusting for the effects of socio-economic factors, racial disparities in prostate cancer incidence and mortality rates remain significant, suggesting a contribution from genetic factors.
  • Dr. Indu Kohaar is using data from a cohort of African American and Caucasian American patients with prostate cancer who have equal access to healthcare and long-term clinical follow-up after initial treatment, to investigate genetic factors that may contribute to prostate cancer racial disparities.
  • Pathogenic and likely pathogenic germline (inherited) variants in known prostate cancer risk genes, as well as a polygenic risk score, will be profiled in the patients in this cohort, to identify any associations with race, age or grade/clinical stage at diagnosis, and patient outcomes.
  • The landscape of tumor mutations in lethal prostate cancer, especially African American patients, will be profiled. Whether there are any associations between germline genetic variants and mutations acquired by tumor cells, and whether such associations impact patients’ disease course or clinical outcomes, will be investigated.
  • If successful, this project will lead to the identification of mutational signatures in aggressive prostate cancer genomes, with an emphasis on racial disparities.

What this means to patients: Understanding the factors that contribute to prostate cancer racial disparities will help to identify solutions to this significant problem. Dr. Kohaar and team will determine how inherited genetic variants may contribute to prostate cancer disparities and impact prostate tumor development and progression. This may enable the development of genetic and genomic biomarker tests to identify individuals at high risk for aggressive prostate cancer, that can be used to guide earlier screening and intervention and improve treatment strategies.