TFRI New Investigator Paul Boutros is among a team of researchers who have found a new test that can help to determine men at high risk for aggressive prostate cancer. The findings, published in The Journal of the National Cancer Institute, could help fill an unmet need for reliable genetic testing for prostate cancer from a simple blood sample. This test would be very similar to how the test for BRCA genes is used to guide treatment for breast cancer.
“The results of our study show that six to 14 per cent of men carried KLK6 gene variants,” says Dr. Boutros, principal investigator, informatics and bio-computing, Ontario Institute for Cancer Research (OICR). “Men with these mutations had three times the risk of developing aggressive prostate cancer. Identifying these patients means that they can more quickly receive the intensive therapy they require and spare patients at lower risk unnecessary therapy. We look forward to seeing these findings improve care for prostate cancer patients worldwide.”
Lead author Dr. Laurent Briollais, senior investigator, Lunenfeld-Tanenbaum Research Institute, Dr. Alexandre Zlotta, director, uro-oncology, Mount Sinai Hospital and Dr. Boutros, along with other collaborators, identified germline mutations in the Kallikrein (KLK) 6 region of the genome that could be used to identify men who harbour the deadliest forms of prostate cancer.
“As an oncologist I know first hand how valuable it would be to have a genetic tool that could help me choose the best course of action with my patients,” explains Dr. Zlotta. “It would help spare patients with indolent disease from unnecessary treatments and their side effects and aid in directing patients with aggressive disease to the appropriate treatment.”
To identify the relevant mutations the scientists analyzed the blood samples of 1,858 patients from three independent groups which included men from Canada, Europe and the U.S.
Dr. Neil Fleshner (Princess Margaret Cancer Centre) was instrumental in providing the study with its Canadian cohort. Through their analysis they found that variations in the KLK6 region were associated with aggressive prostate cancer, defined as those with a Gleason Score of eight or greater. The Gleason Score is used to stratify results of the standard PSA test, which is based upon the KLK3 region (a genomic ‘neighbour’ of KLK6).
The KLK6 variants also independently predicted treatment failure after surgery or radiation for prostate cancer in a fourth independent cohort of 130 men from the Canadian Prostate Cancer Genome Network. Boutros and Dr. Rob Bristow (PMCC) analyzed this cohort using whole genome sequencing.
The tool most routinely used by clinicians to diagnose prostate cancer is a blood test that measures the amount of prostate specific antigen (PSA) in the serum. While the test is useful for identifying men with the disease, it cannot accurately distinguish between those cancers that are likely to lead to death and those that are indolent and pose little threat.
This research was funded by the Canadian Institutes of Health Research, the Ontario Institute for Cancer Research, Prostate Cancer Canada, Movember and the Terry Fox Research Institute.