Scientists have discovered nearly a dozen genes linked to aggressive prostate cancer in the largest study of its kind.
About one in eight American men will develop prostate cancer in their lifetime, making it the most commonly diagnosed form of cancer in men after skin cancer.
Experts don’t know exactly what causes it, but men who carry certain mutations on at least one of these eleven genes have a twofold greater 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.
Researchers analyzed genes that code for proteins 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 detected early using tools such as genetic testing, the survival rate is almost 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 spread, survival drops to 32 percent.
The international team of researchers led by Dr. Burcu Darst, an epidemiologist at USC, analyzed the genes of more than 17,500 men with prostate cancer from Australia, the US, the UK, 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 linked to cancer.
Within that group of more than 17,000, 9,185 men had a life-threatening case of aggressive 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 BRCA2 gene variations were found in just over two percent of cases of aggressive cancer, while it occurred in only 0.7 percent of non-aggressive cases, roughly tripling the risk of developing a life-threatening form of cancer.
ATM mutation errors were also detected in 1.6 percent of aggressive cases and 0.7 percent of non-aggressive cases, more than doubling the risk.
And a damaging variation on the NBN gene was more common in metastatic cases where the cancer has spread to other parts of the body than in milder cases.
The researchers selected eight other genes whose mutations, although 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 the gene mutations identified by researchers.
Men who carried rare harmful gene mutations in one of eleven genes had a twofold increased risk of progressing to a fatal disease.
There are some genes, the researchers found, that are included in extensive genetic testing because they increase the risk of cancer, but they shouldn’t be.
Dr. Christopher Haiman, a cancer researcher at USC, said: ‘Some genes in these panels were based on small studies and were not associated with prostate cancer in our study.
‘We have also found indications that other genes may need to be added. The results are not yet completely definitive, but it is clear that more work needs to be done to determine which genes oncologists should focus on when testing.”
Genetic testing is a valuable tool in oncology because it provides doctors with crucial time to intervene if a problematic mutation is detected.
With a better understanding of what our genes can tell us about future encounters with disease, an emerging area of research has emerged into targeted drugs that repair gene abnormalities that cause cancer.
Doctors can now insert tumor suppressor genes into a person’s cells, or directly into cancer cells that then destroy themselves.
Dr. Haiman said: ‘While the screening focuses on men with advanced disease or a family history, finding patients with less advanced disease who carry these genetic variants could allow them to receive earlier targeted forms of treatment.’
Their findings were published in the journal JAMA Oncology.
That is more than 288,000 men expect to get prostate cancer this year, a pace that has gathered pace in recent years.
Just over 201,000 new cases were reported in 2020, up from around 192,000 in 2016.
In the US, it is up to the patient and his doctor whether to be screened for prostate cancer. There is no mandate for screening, although general guidelines recommend that men undergo prostate-specific blood tests every two to three years.