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2021 PCF Young Investigator Award

Investigating Whether a Healthy Lifestyle or Pharmacological Intervention can Offset the Risk of Lethal Prostate Cancer in Men at High Genetic Risk

Anna Plym, PhD
Harvard: Brigham and Women’s Hospital

Mentors: Lorelei Mucci, ScD, Adam Kibel, MD

Description:

  • Prostate cancer is the most heritable of all cancers, with genetic factors accounting for a large proportion of cases. Recently, 269 single nucleotide polymorphisms (SNPs) associated with prostate cancer were identified, accounting for a significant proportion of prostate cancer heritability. These SNPs have been combined into a polygenic risk score that is highly predictive of prostate cancer across ethnic groups, with a lifetime risk of over 50% in men at highest genetic risk.
  • Given the excess risk of prostate cancer among men with a high polygenic risk score and among carriers of rare genetic variants in DNA repair genes, there is an urgent need to provide men evidence-based recommendations on possible modifiable factors that could reduce their risk.
  • Dr. Anna Plym is studying whether a favorable lifestyle and diet or common pharmacological interventions could reduce genetic risk for prostate cancer.
  • In this project, Dr. Plym will utilize epidemiologic and genetic data from three large prospective cohort studies, including one which has a high representation of black men, to evaluate if men with a high polygenic risk score can offset their risk of lethal prostate cancer by adhering to a healthy lifestyle, including maintaining a healthy weight, engaging in regular physical activity, eating a healthy diet, and not smoking.
  • Whether prostate cancer patients with germline mutations in DNA repair genes (including BRCA1, BRCA2, and ATM) can offset their risk of lethal prostate cancer by adhering to a healthy lifestyle will also be evaluated.
  • The impact of common pharmacological treatments (including aspirin, statins, and finasteride) on lethal prostate cancer in men at high genetic risk will also be evaluated in these cohorts.
  • If successful, this project will identify modifiable risk factors to reduce lethal prostate cancer in men at high genetic risk. This will inform design of clinical trials on lifestyle interventions and evidence-based recommendations on optimal healthy lifestyle choices for men at high genetic risk and their families.

What this means to patients: As tools for identifying men at high genetic risk for prostate cancer improve and become more widely used, it will be important to provide evidence-based recommendations on possible modifiable factors that could reduce risk. Dr. Plym will identify lifestyle, dietary, and common pharmacological treatments that can reduce genetic risk for prostate cancer, which will inform future interventional clinical trials and lifestyle recommendations for patients and their families.