Sequencing to Identify Predisposition Genes for Recurrent/Lethal Prostate Cancer

Each year, about 300,000 American men are diagnosed with prostate cancer (PRCA), the most common cancer in the western world after skin cancer. Decades of investigation into the genetic causes of PRCA have yet to identify genes or variants that explain more than a small fraction of cases. Even less progress has been made into understanding why approximately one-third of patients with localized PRCA develop recurrent and subsequently metastatic and fatal cancer.

This study, led by Lisa Cannon-Albright, PhD, will be the first to specifically target the genetics of metastatic/lethal PRCA in families that are predisposed to developing the disease. Her team has already identified and recruited over 550 families that are at high risk for developing prostate cancer, and sampled over 10,000 members. Of these, 223 lethal PRCA cases cluster in 45 high-risk families.

The team’s gene discovery efforts are starting with eight families, focusing on sequencing pairs of first cousins with lethal PRCA. The rationale is that the cousins’ genomes will mostly differ from one another, except that both should carry the same PRCA predisposition gene that runs in their family. This genetic strategy should enhance the power to filter out false positives and identify the predisposition gene(s).

The eventual identification of PRCA predisposition genes, accompanied by a greater understanding of how they ultimately lead to mortality, will lead to the development of diagnostic tests and more personalized treatments for the most serious cases of PRCA.