Genetic testing: Important in management and treatment of prostate cancer
A recent study led by Burcu F Darst, PhD (University of Washington and Fred Hutchinson Cancer
Research Center) investigated the connection between specific genes and the development of aggressive prostate cancer. Gene testing is currently recommended for men who have advanced prostate cancer or a family history of the disease. However, there is limited evidence about the role of some genes currently included in genetic panel tests. These tests might also miss certain genes that are important in assessing prostate cancer risk, especially those that influence whether the cancer becomes aggressive. The study’s goal was to identify genes that are associated with aggressive forms of prostate cancer, which could help improve how the disease is managed.
The researchers conducted a large genetic association study focusing on men of European ancestry. The study involved 17,546 men, with 9,185 having aggressive forms of prostate cancer (including 6,033 who died from the disease and 2,397 whose cancer had spread) and 8,361 men with nonaggressive prostate cancer. The research was done in two stages to analyze genetic variations across the genome. Special attention was given to 29 genes involved in DNA repair and cancer susceptibility. These genes are often included in genetic tests for prostate cancer.
The study found strong evidence that rare, harmful variants in the BRCA2 and ATM genes are linked
to aggressive or metastatic prostate cancer. Men who had these variants were more likely to develop
severe forms of the disease compared to those without these
mutations. The NBN gene also was associated with aggressive prostate cancer although the evidence was not as strong as for BRCA2 and ATM. Additionally, some evidence was found for other genes, such as MSH2, XRCC2, and MRE11A. While genes like TP53, RAD51D, and BARD1 showed a higher risk of aggressive prostate cancer, the differences in frequency of these variants between men with aggressive and nonaggressive cancer were not statistically significant.
Overall, 2.3% of men with non- aggressive prostate cancer had harmful variants in these genes, compared to 5.6% of men with aggressive prostate cancer and 7.0% of men whose cancer had metastasized (spread to other parts of the body).
The study provides further evidence that DNA repair and cancer susceptibility genes play a critical role in prostate cancer development. The findings suggest that genetic testing should not be limited to men with advanced prostate cancer. Men with nonaggressive prostate cancer who carry harmful variants of these genes may still be at risk for developing more aggressive disease at a later time. Extending testing could lead to better disease management and more personalized treatment plans.
JAMA Oncol. 2023 Nov 1;9(11):1514-1524. doi: 10.1001/jamaoncol.2023.3482
