Scientists have discovered nearly a dozen genes linked to aggressive prostate cancer in the largest study of its kind.
Approximately one in eight American men will suffer from prostate cancer in their lifetime, making it the most commonly diagnosed male cancer, second only to skin cancer.
Experts don’t know exactly what causes it, but men who carry certain mutations in at least one of these 11 genes have a two-fold increased risk of life-threatening prostate cancer, their study found.
The discovery, led by scientists at the University of Southern California, could pave the way for more innovative cancer screening tools and targeted gene therapies.
The researchers analyzed protein-coding genes using blood samples collected from more than 17,500 European men with prostate cancer.
Nearly 13 percent of American men will develop prostate cancer during their lifetime. When caught early using tools like genetic testing, the survival rate is nearly 100 percent.
Nearly 100 percent of men whose cancer is caught early before it spreads to other parts of the body will survive. But once the cancer has metastasized, survival drops to 32 percent.
The international team of researchers led by Dr. Burcu Darst, a USC epidemiologist, analyzed the genes of more than 17,500 men with prostate cancer from Australia, the United States, the United Kingdom, Finland, Sweden and other European countries.
They did this by analyzing blood samples collected between January 2021 and March 2023. The team focused on a subset of about 1,700 genes that have been associated with cancer.
Within that group of more than 17,000, 9,185 men had a case of aggressive, life-threatening prostate cancer.
Two mutated genes in particular showed strong associations with severe cases: BRCA2, one of the best-known genes linked to breast cancer risk, and ATM, which plays a crucial role in repairing damaged DNA.
Harmful variations of the BRCA2 gene were found in just over two percent of aggressive cancer cases, while they appeared in only 0.7 percent of non-aggressive cases, approximately tripling the risk of contracting a potentially fatal form of cancer. .
Likewise, ATM mutation defects were discovered in 1.6 percent of aggressive cases and 0.7 percent of non-aggressive cases, more than doubling the risk.
And a harmful variation of the NBN gene was more common in metastatic cases where the cancer has spread to other parts of the body compared to milder cases.
The researchers selected eight other genes whose mutations, while associated with more aggressive prostate cancer, had a slightly weaker association: MSH2, XRCC2, MRE11A, TP53, RAD51D, BARD1, GEN1 and SLX4 i.
Study participants did not have to have all of the genetic mutations identified by the researchers.
Men who carried rare harmful genetic mutations in any of the 11 genes had a two-fold increased risk of progressing to a fatal disease.
Researchers found that there are some genes that are included in comprehensive genetic testing because they increase cancer risk, but they shouldn’t be.
Dr. Christopher Haiman, a cancer researcher at USC, said, “Some of the genes in these panels were based on small studies and were not associated with prostate cancer in our study.
‘We also found evidence that perhaps other genes should be added. The results are not completely definitive, but it is clear that more work is needed to determine which genes oncologists should focus on in testing.’
Genetic testing is a valuable tool in oncology, giving doctors crucial time to intervene if a problematic mutation is detected.
With greater understanding of what our genes can tell us about future encounters with disease, there has been an emerging field of study on drugs aimed at repairing genetic abnormalities that cause cancer.
Doctors can now insert tumor suppressor genes into a person’s cells, or directly into cancer cells that then self-destruct.
Dr. Haiman said, “While screening focuses on men with advanced disease or a family history, finding patients with less advanced disease who carry these genetic variants may allow them to receive specific forms of treatment sooner.”
Their findings were published in the journal JAMA Oncology.
More than 288,000 men are expected to have prostate cancer this year, a pace that has accelerated in recent years.
In 2020, just over 201,000 new cases were reported, compared to about 192,000 in 2016.
In the US, whether you can get screened for prostate cancer depends on the patient and their doctor. There is no mandate for screening, although general guidelines recommend that men undergo prostate-specific blood tests every two to three years.