Study findings suggest adding the CDK12 variant to hereditary screening panels could help identify men at risk for early-onset disease.
A gene variant that can be passed through families may increase the risk of developing early, aggressive prostate cancer, according to researchers at the University of Washington School of Medicine and the University of British Columbia.
The study, published in the journal Cancer Discovery, suggests that the gene, called CDK12, should be included in standard cancer-risk screening panels. Men found to have these variants might consider earlier screening for prostate cancer, though researchers note that more work is needed to guide specific recommendations.
“The patients we identified in the study were diagnosed with prostate cancer at a younger age and had an aggressive form of the disease — all the hallmarks of the type of cancer you would want to screen for,” says Colin C Pritchard, professor of laboratory medicine and pathology at the University of Washington School of Medicine, in a release. Pritchard served as co-senior author of the paper alongside Alexander Wyatt, associate professor in the department of urologic sciences at the University of British Columbia.
DNA Repair and Cancer Risk
The CDK12 gene codes for a protein involved in regulating DNA repair. While cells carry two copies of the gene, the cell can typically repair DNA damage if at least one copy is functional. However, if both copies are defective, the repair process is impaired, which can lead to the development of cancer.
For the study, researchers sequenced the coding region of CDK12 in tumors from 4,535 men with aggressive prostate cancer. These sequences were compared with CDK12 sequences in the men’s non-cancerous white blood cells, which reflect inherited DNA.
The team identified five men who inherited one normal copy and one defective copy of CDK12. In their cancer cells, the normal copies had mutated, providing clues that the disruption of CDK12 activities could lead to more aggressive cancers.
The researchers also found that several family members of these patients had early-onset prostate cancer, and two sisters in one of the families had ovarian cancer. The potential role of inherited CDK12 variants in ovarian cancer warrants further investigation, according to the researchers.
Clinical Implications for Testing
Based on the findings, the researchers concluded that CDK12 should be included in hereditary cancer-risk panels for individuals who meet testing guidelines for a history of prostate cancer and other cancers.
Adding CDK12 to these panels would be simple to implement, according to Pritchard. The gene is already included in panels used to identify treatment options for cancer patients, but it is not currently included in most genetic testing panels for inherited risk.
“These inherited CDK12 variants are rare and may not affect hundreds of thousands of people, but the people who have it will want to know, as it may have important implications for their care and for their relatives,” says Pritchard in a release.
The research was funded in part by grants from the US Department of Defense and the National Institutes of Health.
Photo caption: Clinical pathologist Dr Colin Pritchard in his cancer molecular diagnostics research lab.
Photo credit: UW Medicine
