A rare inherited gene change may help explain why some men develop aggressive prostate cancer at a younger age, according to new international research.
The finding does not mean most prostate cancers are inherited. Most are not. But it may help doctors identify a small number of families who face a higher risk and could benefit from earlier monitoring or genetic counselling.
Researchers led by the University of British Columbia found inherited changes in a gene called CDK12 in several men with aggressive prostate cancer. All five men identified in the main analysis had metastatic disease, meaning the cancer had spread beyond the prostate, by the time they were diagnosed.
The study was published in Cancer Discovery.
What is already known about inherited cancer risk
Cancer usually develops after genetic changes build up in cells during a person’s life. These changes are not usually passed on to children.
A smaller proportion of cancers, around 5% to 10%, are linked to inherited gene changes. These are present from birth and can be passed through families.
The best-known examples are changes in the BRCA1 and BRCA2 genes. These can raise the risk of several cancers, including breast, ovarian, pancreatic and prostate cancer. Testing for BRCA changes has become an important part of cancer care for some patients and families, because it can guide screening, prevention and treatment decisions.
The new research suggests that CDK12 may be another gene to consider in hereditary prostate cancer, although the mutation appears to be very rare.
What the new study found
The evidence comes from human genetic data.
Researchers analysed genetic information from more than 4,500 people with aggressive prostate cancer. They identified five unrelated men who carried inherited CDK12 mutations.
All five developed metastatic prostate cancer between the ages of 44 and 62. This is relatively young for advanced prostate cancer, which is more common in older men.
In plain language, the main finding is this: a small number of men with aggressive prostate cancer were born with damaging changes in CDK12, and their tumours showed signs that this inherited change was likely involved in the cancer’s development.
The researchers estimated that inherited CDK12 mutations may be present in about one in every 1,000 people with aggressive prostate cancer.
How CDK12 may contribute to cancer
Genes act as instructions for how cells grow, repair themselves and carry out their normal functions. When a gene that helps control cell behaviour is damaged, cells may become more likely to grow abnormally.
CDK12 is involved in important cellular processes, including the way cells manage genetic information and maintain stability in their DNA. If a person inherits a harmful CDK12 change, every cell in the body carries one altered copy of the gene.
Cancer can develop if the remaining working copy is lost or damaged in prostate cells. At that point, CDK12 may no longer function properly in those cells.
The researchers looked for a specific pattern of genetic changes in the tumours, described as a genetic signature. This signature suggested that CDK12 had stopped working and that the inherited mutation was not just an incidental finding.
This is important because CDK12 mutations were previously thought to occur only within tumour cells during a person’s lifetime, rather than being inherited.
How strong is the evidence?
The study provides strong evidence that inherited CDK12 mutations can be linked to aggressive prostate cancer in some families. The use of tumour genetic signatures strengthens the case that the mutations were biologically relevant.
However, the number of people identified was small. Only five unrelated men with inherited CDK12 mutations were found in the main prostate cancer analysis.
That means several questions remain. Researchers do not yet know the exact lifetime risk of prostate cancer for someone who inherits a harmful CDK12 mutation. They also do not know how risk may vary by family history, ancestry or other genetic factors.
The finding is therefore important, but still emerging. It should not be interpreted as meaning that CDK12 mutations are a common cause of prostate cancer.
What this means for patients and families
For the general public, this study does not change routine prostate cancer advice.
Men should continue to follow existing guidance and speak with a healthcare professional if they have urinary symptoms, a strong family history of prostate cancer, or concerns about their personal risk. Symptoms can include difficulty passing urine, needing to urinate more often, blood in urine or semen, or unexplained pelvic or back pain. Many urinary symptoms are not caused by cancer, but they should be assessed.
For families with a history of early or aggressive prostate cancer, the findings may become more relevant. If CDK12 is added to genetic testing panels, identifying one affected person could allow relatives to be offered counselling and, where appropriate, testing.
This kind of testing should be done through clinical genetics or specialist cancer services, because results can affect relatives as well as the person being tested.
Could this change genetic testing?
The researchers say the results support adding CDK12 to standard genetic testing panels for hereditary prostate cancer.
This may be practical because the technology used to detect inherited cancer-risk genes already exists. Many genetic testing panels can be updated to include additional genes when evidence supports doing so.
For patients, the possible benefit is earlier identification of those at increased risk. Earlier detection of prostate cancer may allow treatment while the disease is still curable.
However, screening and testing programmes need careful design. Genetic testing can produce uncertain results, and not every inherited gene change has the same level of risk. People offered testing should receive clear information about what the result can and cannot tell them.
Possible link with ovarian cancer
The study also raises the possibility that inherited CDK12 mutations may be linked to ovarian cancer.
Several of the men with CDK12 mutations had family histories of ovarian cancer. The researchers also identified a person with ovarian cancer who carried an inherited CDK12 mutation, and whose tumour showed a similar genetic pattern.
This finding is preliminary. It does not yet prove that CDK12 mutations increase ovarian cancer risk, but it gives researchers a reason to investigate the link in larger studies.
What remains uncertain
Further research is needed to answer several key questions.
Scientists need to confirm the finding in larger and more diverse groups of patients. They also need to estimate how much an inherited CDK12 mutation raises cancer risk, and whether risk differs between men and women.
It is also not yet clear when screening should start for people who carry these mutations, how often it should take place, or which tests would provide the best balance of benefit and harm.
Another question is whether CDK12 status could affect treatment choices for people who already have prostate cancer. Some tumour gene changes can guide the use of targeted medicines, but the clinical meaning of inherited CDK12 mutations will need further study.
A rare finding with practical importance
This research identifies a rare inherited form of prostate cancer risk linked to CDK12 mutations. The mutation appears to affect only a small proportion of people with aggressive prostate cancer, but it may matter greatly for families who carry it.
The main message is not that most men need new genetic testing now. Rather, the study suggests that CDK12 should be considered in specialist genetic testing for hereditary prostate cancer, especially where disease is aggressive or occurs at a younger age.
For cancer care, the finding adds one more piece to a growing effort to identify inherited risk earlier, guide screening more precisely and give families clearer information about their health.
The post New Rare Inherited Risk Linked to Aggressive Prostate Cancer in Young Men first appeared on PP Health Malaysia.
