Prostate cancer and DNA mutation: New connections revealed

Specific mutations in the DNA of men with metastatic prostate cancer have been shown to play a larger role in the disease than previously thought. Researchers hope that this finding will help change standard therapy guidelines and open the door to drugs currently being used for other cancers.

These gene mutations were already known to occur more frequently in prostate cancer patients than the general population.

However, the present study demonstrated that mutations in DNA repair genes were even more prevalent in people with metastatic prostate cancer, specifically.

The research was headed up by Dr. Peter Nelson, a member of the Human Biology, Clinical Research, and Public Health Sciences divisions at Fred Hutchinson Cancer Research Center, WA.

The team found that more than 10 percent of men with aggressive prostate cancer displayed inherited mutations in DNA repair genes.
These particular mutations occur in DNA repair genes such as BRCA1 and BRCA2, both of which produce tumor suppressor proteins.

These DNA repair genes, as the name suggests, help maintain the integrity of the genetic code. If they are mutated, the DNA is less likely to be repaired correctly, increasing the risk of cancer.

BRCA1 and BRCA2 genes are already known to increase the risk of female breast and ovarian cancer. These two genes alone account for 20-25 percent of all hereditary breast cancers.

So, although the role of these genes in cancer is known to be important, their influence in metastatic prostate cancer was not fully recognized.

DNA repair genes and metastatic prostate cancer
The researchers found that 11.8 percent of men with metastatic prostate cancer (regardless of age or family history) had mutations in one of the 20 DNA repair genes they screened for. That's around four times the rate found in the general population and twice as much as the rate found in men with localized prostate cancer.

BRAC2 showed the clearest change in gene prevalence; men with advanced prostate cancer were 18 times more likely to have a mutation in their BRCA2 gene when compared with men without prostate cancer.

The researchers state their results are important for men who have ben diagnosed, as well as for family members who might be at risk:

"The result is surprising and important for men with prostate cancer as this information may prioritize certain therapies. It is also important for family members as they may have inherited a gene that predisposes them to developing one of several types of cancer, and heightened awareness could enhance early detection and treatment."

Dr. Peter Nelson

In total, the research team used data from 692 men with metastatic prostate cancer across a number of sites, including the Fred Hutchinson Cancer Research Center and the University of Washington. All of the institutions involved in the study carried out independent screening of 20 distinct DNA repair genes.

Importantly, the men used in the current study were not chosen because of family history or age, giving the results extra reliability. Additionally, the independent screening across multiple laboratories produced the same results across the board, adding further strength to the findings.

The future treatment of prostate cancer
This research project could open the door to other forms of treatment for metastatic prostate cancer. PARP inhibitors and platinum drugs are already used in some cancer cases, such as treating ovarian cancer in people with DNA repair gene mutations.

PARP inhibitors - poly (ADP-ribose) polymerase - prevent PARP from repairing the damaged DNA of cancer cells, steadily killing them off.

Platinum drugs, including cisplatin, carboplatin, and oxaliplatin, also inhibit DNA repair, slowly destroying cancer cells which are unable to fix their faulty genes. The results of this study could lead to the approval of PARP inhibitors and platinum drugs for metastatic prostate cancer, improving overall chances of survival.