Genes, mutations, and your family tree: The hereditary and genetic factors that can influence prostate cancer outcomes



The connection between a man’s genes and his risk of developing prostate cancer is well established, but not well understood. Around 5-10% of all Australian prostate cancer cases are caused by an inherited genetic risk, and around 10-12% of men with metastatic castration-resistant prostate cancer carry inherited BRCA1/2 mutations. In other cases, acquired genetic mutations can increase a man’s risk of developing the disease and influence how aggressive it becomes.

Fact: If your father or brother have ever been diagnosed with prostate cancer, you have twice the average risk of developing the disease.

If you have two or more close male relatives who have been diagnosed, your lifetime risk of developing prostate cancer increases five-fold.

And your risk also increases if you have a strong family history of breast or ovarian cancer, especially if a BRCA1 or 2 gene mutation was involved.

However, making a connection between your family history and the genes responsible for prostate cancer is an area of ongoing research, with much to reveal about how we can treat the disease in future.

Here’s what we know:

  • All of us have Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2) genes. They are tumour suppressor genes that function to repair cell damage which help to prevent certain cancers from developing. When your BRCA1 and 2 genes have mutations, your risks of related cancers increases.
  • About 1 in 500 Australians carry a BRCA1 mutation and 1 in 225 have a BRCA2 mutation.
  • Men who have the BRCA1 mutation have a 9% risk of developing prostate cancer, compared to the population average risk of just 5%. These men also have a 1% risk of developing breast cancer.
  • Men who have the BRCA2 mutation have a 15% risk of developing prostate cancer compared to the population average, and a 7% risk of developing breast cancer, compared to the population average of much less than 1%.

Research has found that if prostate cancer develops in a man who carries a BRCA1 or BRCA2 mutation, it more likely to be aggressive and to spread beyond the prostate.

While our current understanding suggests that only 5 to 10% of all prostate cancer cases in Australia are caused by an inherited genetic risk, about 10 to 12% of men with metastatic castration resistant prostate cancer have BRCA mutations.

More interesting still, only around half of these are inherited mutations, and about 5% of men with advanced prostate cancer have non-inherited BRCA1 or 2 mutations.

Gene testing and new medicines

Australian men with advanced prostate cancer now have access to precision medicines that can help stop the spread of tumours linked to genetic variations. In parallel, new research is looking at whether genetic testing should be more widely introduced to help target genetic variants that may be driving some forms of the disease.

In April 2022 the Australian government listed AstraZeneca’s Lynparza® (olaparib) for eligible men with prostate cancer, responding to a lengthy advocacy campaign by PCFA and others.

Since then, thousands of men have benefitted from no-cost genetic tests and access to the life-extending drug, which has been found to lower men’s risk of death by 31% compared to other forms of treatment.

The drug, known as a PARP Inhibitor, works by blocking proteins that promulgate cancer growth, but is only effective in men with cancers linked to BRCA gene mutations which cause prostate cancers to become more aggressive.

Evidence shows that men diagnosed with prostate cancer who have mutations in the BRCA1 or BRCA2 genes have higher risks of more aggressive prostate cancers and poorer clinical outcomes. 

In particular, men with faults in their BRCA2 gene are five times more likely to be diagnosed with prostate cancer and at a younger age and this high-risk group is twice as likely to have a more serious, potentially life-threatening, form of prostate cancer.

One of the advantages to Lynparza is that it is taken twice daily as a tablet, with a relatively low risk of serious adverse events and side-effects among patients.

In terms of treatment pathways, it’s offered to men when their prostate cancer becomes resistant to other forms of treatment, which means it’s important for men with advanced prostate cancer to undergo genetic testing early so that we can determine whether to target the tumour with Lynparza or other novel medicines.

Identifying BRCA-mutations in mCRPC as early as possible has the potential to change the way we manage advanced prostate cancer, slowing down the spread of the disease and improve overall survival time.

Call our Telenursing team today on 1800 22 00 99 to get individual advice or email for more information. 

What can you do about family and genetic risks?

Firstly, know your family history, and talk to your GP about screening for prostate cancer from 40 years old.

Secondly, remember that few men experience any symptoms of prostate cancer at its earliest stages, so don’t be fooled by how well you feel.

Thirdly, support research and advocacy in this area. Research has led to breakthroughs in precision medicine that allow us to target BRCA1 and 2 prostate cancers with new drugs.