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2022 Michael & Lori Milken – PCF Young Investigator Award

Functional and Treatment Implications of a Rare Germline HOXB13 Variant Affecting Risk of Lethal Prostate Cancer in Patients of African Ancestry

Mayuko Kanayama, MD, PhD
Johns Hopkins University

Mentors: Jun Luo, PhD, Tamara Lotan, MD, William Isaacs, PhD

Description:

  • Prostate cancer incidence and mortality is disproportionately high in patients of African descent. Many factors likely contribute to this disparity, including genetics, modifiable risk factors (e.g., diet, lifestyle), and unequal heath care access.
  • Certain inherited variants in the HOXB13 gene are known to increase risk for prostate cancer. Dr. Mayuko Kanayama and others have recently identified and characterized a HOXB13 gene variant found specifically in patients of African ancestry that is associated with increased risk for aggressive prostate cancer and earlier age at diagnosis.
  • In this project, Dr. Kanayama will define the functions of this HOXB13 variant in prostate cancer and determine whether it impacts response to various prostate cancer treatments, compared with a variant specific to European ancestry, and to “wild type” HOXB13.
  • If successful, this project will establish rationale for screening patients of African ancestry for this variant and will identify effective treatment strategies for prostate cancer patients carrying this variant.

What this means to patients: Patients of African ancestry have a disproportionately high rate of prostate cancer incidence and mortality, the causes of which are multifactorial and unclear. Dr. Kanayama is investigating the contributions of a newly discovered variant in a prostate cancer risk gene that is found in people of African ancestry, and will determine how this variant impacts prostate cancer development and treatment responses, in order to develop new screening and treatment strategies for patients.