Mutations in KLK6 Gene Region Can Predict Risk of Aggressive Disease in Prostate Cancer Patients

Mutations in KLK6 Gene Region Can Predict Risk of Aggressive Disease in Prostate Cancer Patients

Genetic mapping of the Kallikrein 6, or KLK6, gene region — which could be a hotspot for the occurrence of prostate cancer-associated mutations — may help doctors identify which patients are at risk of developing an aggressive form of the disease, according to Canadian researchers.

Their study, “Germline Mutations in the Kallikrein 6 Region and Predisposition for Aggressive Prostate Cancer,” recently appeared in the Journal of the National Cancer Institute.

“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,” the study’s senior author, Alexandre Zlotta, MD, said in a press release. “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.”

Zlotta is director of uro-oncology at Toronto’s Mount Sinai Hospital, and researcher with the Lunenfeld-Tanenbaum Research Institute. Also on the team was Paul Boutros, MD, principal investigator at the Ontario Institute for Cancer Research (OICR).

The study evaluated the occurrence of genetic alterations in the Kallikrein (KLK) genetic region in a cohort of 1,858 men with aggressive prostate cancer. This region is known to encode a family of 15 genes, including the Kallikrein 3 gene, which codes for the PSA protein. Eventually, researchers identified five specific mutations in the KLK6 region that were present in 6 to 14 percent of prostate cancer patients.

These mutations were present in six to 14 percent of prostate cancer patients, and caused a threefold increased risk of aggressive disease. The presence of KLK6-associated mutations in a cohort of 130 men from the International Cancer Genome Consortium (ICGC) also showed that they could predict prostate cancer treatment failure.

Furthermore, men with KLK6 mutations who underwent surgical and radiation therapy were three times more prone to relapse than those without such mutations. The findings suggest that the KLK6 region can help fill the unmet need for a predictor of prostate cancer aggressiveness, since the PSA test currently determines a patient’s risk of prostate cancer, but not its severity.