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New insights into predicting the most aggressive forms of prostate cancer

March 14, 2017

 

Most prostate cancer (Pca) is diagnosed through a blood test, serum PSA testing. The well appreciated down-side of PSA testing is the diagnosis of a considerable proportion of indolent cancers that are highly unlikely to progress to clinically significant, lethal disease. Our limited ability to accurately identify men destined to suffer and die from the disease from the majority of indolent cases is a major concern and contributes to the dilemma regarding Pca screening and its genetic testing. There is therefore an unmet need to develop genetic tests that can predict whether a man specifically is highly susceptible to the aggressive form of prostate cancer. In some other cancers, such as breast and ovarian cancer, certain predictors of aggressiveness (e.g. BRCA gene mutations) have proven effective in identifying subsets of patients for specific interventions.

In prostate cancer, genetic testing to predict the individual risk to Pca is not performed routinely because of the absence of a marker which accurately identifies aggressive prostate cancer. In a new study published in the Journal of the National Cancer Institute, Dr. Alex Zlotta and colleagues identified a new region within the Kallikrein gene, the Kallikrein 6 gene region, detectable in the blood, that is strongly associated with aggressive prostate cancer (defined as Gleason Score ≥8) in a cohort of 1858 men from three continents. The team developed a blood test at the Lunenfeld-Tanenbaum Research Institute which detects variants of this Kallikrein 6 gene. The test was validated in three independent cohorts including unique cohorts from large international screening studies for prostate cancer.
The Kallikrein 6 gene variants identified also independently predicted treatment failure after surgery or radiation for prostate cancer in a fourth independent cohort. The frequency of the gene variants varied from 6 to 14% in the population and the increased risk of aggressive prostate cancer was multiplied by almost 3 times in men who harboured the mutations.

Most studies to date have focused on the risk of prostate cancer , not the specific risk of aggressive lethal prostate cancer. The demonstration that germline variants of a new gene, Kallikrein 6, are strongly associated with aggressive prostate cancer, may be of high value in the management of the most common cancer in men.

This research was funded by the Canadian Institutes of Health Research (CIHR), the Ontario Institute for Cancer Research (OICR), Prostate Cancer Canada (Movember initiative), a Terry Fox Research Institute New Investigator Award and a CIHR New Investigator Award.

This paper is dedicated to the memory of our long time colleague and dear friend, Dr. Hilmi Ozcelik.

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