Gene Mutations Associated with Aggressive Prostate Cancer

An international study has identified inherited genomic DNA mutations in the Kallikrein 6 (KLK6) gene region that are connected to a predisposition for some men to develop aggressive prostate cancer (PC).

Much like diagnostic tests developed based on association between BRCA gene mutation and risk for breast cancer in women changed the approach to prevention and treatment, discovery of the KLK6 region’s connection to aggressive PC may change the course of PC patient care.

The study was led by Dr. Alexandre Zlotta of Mount Sinai Hospital and Lunenfeld-Tanenbaum Research Institute, part of Sinai Health System in (Toronto, Ontario, Canada) and Dr. Paul Boutros of Ontario Institute for Cancer Research (OICR). Early diagnosis of aggressive PC is an important unmet need. Up until now, no single test could predict severity of PC type - the current PSA test (based on KLK3, which is located near KLK6) only identifies the risk of PC, not its severity.

“As an oncologist I know firsthand how valuable it would be to have a genetic tool that could help choose the best course of action with my patients,” explained Dr. Zlotta, “It would help spare patients with indolent disease from unnecessary treatments and their side-effects and aid in the diagnosis and directing patients with aggressive disease to the appropriate treatment.”

To identify relevant mutations the researchers analyzed blood samples of 1,858 men from 3 independent cohorts in Europe and North America. The study showed a 3-fold increase in the risk of aggressive PC for men with the KLK6 mutation. The frequency of the gene variants varied from 6-14% of the population of men with PC.

The KLK6 variants also independently predicted treatment failure after surgery or radiation for PC in another independent cohort of 130 men.

The study, by Briollais L et al, was published March 14, 2017, in the Journal of the National Cancer Institute (JNCI).