Of all the different types of cancer, prostate cancer is one with some of the strongest links to the family tree. The inherited risk of developing prostate cancer due to genetic factors has been estimated to be as high as 57%. As a result, there has been a large push for research to identify where exactly in the genetic profile this risk comes from and whether these genes are passed down through ancestry.
We already know that mutations in certain genes – specifically those that are responsible for repairing the DNA of cells in our body – can increase cancer risk. A gene mutation like this disrupts the normal function of the genes involved in repairing damaged DNA, and so far, more than 100 variants have been found. These include mutations in BRCA1, BRCA2, MSH2, and HOXB13. The most common mutation of this type is involves the BRCA2 gene, which is linked with significantly increased risk of cancers of the breast, ovaries, prostate, colon, pancreas, as well as melanoma. It is linked with 1.8% of overall prostate cancer cases.
Weill Cornell Medicine and NewYork-Presbyterian served as one of the main research sites in a recently-published multi-institutional study which found that 11.8% of men with metastatic prostate cancer had DNA-repair gene mutations. This is significantly higher than the prevalence among men with localized prostate cancer (4.6%). These mutations are associated with more aggressive and fatal cancers, so it makes sense that a higher percentage was found in those with metastatic disease.
This study also showed a link between having DNA-repair mutations and a family history of prostate cancer. Genetic testing is very important because inherited mutations in genes that affect DNA repair plays an important role in identifying family members who also may be at increased risk (and not just for prostate cancer), deciding the best course of treatment, and in decision making in screening for other cancers. Knowing this information presents an opportunity for precision medicine in order to customize treatment for each patient.
PARP1 is an enzyme that has emerged as a new drug target for cancer therapy and certain cancer treatments, such as PARP1-inhibitors have been shown to be more effective in prostate cancer patients with these DNA-repair mutations. Men with metastatic prostate cancer and these mutations also frequently respond to platinum chemotherapy.
Additionally, it is known that twins are more affected and early-onset cancer may result from germline alterations so young men with prostate cancer are being studied to figure out which genes may be linked with a prostate cancer diagnosis at an early age.