Genomics in general practice

Disease specific topics

Familial prostate cancer

Familial prostate cancer


A comprehensive family history must be taken and regularly updated to identify patients who may be at risk of familial prostate cancer. 

Use existing risk criteria to identify individuals who are at increased risk of carrying a pathogenic variant A pathogenic variant is a genetic variant that increases an individual’s susceptibility or predisposition to certain diseases. Pathogenic variants are also known as mutations. of the BRCA1 or BRCA2 genes (high risk). These individuals should be referred to a family cancer clinic. 

Men with family history of prostate cancer who decide to be tested should be offered prostate-specific antigen (PSA) testing every two years from 40 or 45 years of age, with the starting age depending on the strength of their family history.

What do I need to know?

Approximately 1–2% of prostate cancer is due to pathogenic variants in the BRCA1 and BRCA2 genes. These show an autosomal dominant inheritance When a condition follows an autosomal dominant pattern of inheritance, the family tree will usually reveal multiple affected members in multiple generations on the same side of the family. Dominant conditions or traits are expressed when only a single gene variant is inherited. Wide variability in clinical expression is common in many autosomal dominant conditions, even within the same family. Early onset of conditions, such as cancer, can be indicative of autosomal dominant inheritance within a family. Not all dominant conditions show 100% penetrance (eg BRCA1 gene mutations). pattern.

Multiple genetic and environmental factors are likely to influence the risk of prostate cancer. Genetic testing for gene variants Gene variants are small DNA sequence changes (ie additions, duplications, deletions, substitutions). These variants can have a range of effects: some may cause disease (pathogenic variant), while others do not cause disease but may modify an individual’s risk of disease (i.e may increase risk or provide a protective effect). The vast majority of gene variants are benign and do not result in disease but rather contribute to the differences between people. in men with multiple cases of prostate cancer only in their family is not widely available.

Features suggestive of increased risk of having a pathogenic BRCA1 or BRCA2 variant include two or more relatives affected by breast or ovarian cancer on the same side of the family (maternal or paternal) plus an additional high-risk feature:

  • relatives with breast or ovarian cancer
  • breast and ovarian cancer in the same woman
  • breast cancer diagnosed <50 years of age
  • Ashkenazi Jewish ancestry
  • bilateral breast cancer
  • male breast cancer

A three-generation family history is key to identifying high-risk families who are most likely to benefit from genetic assessment. Such a history should include first-degree and second-degree relatives on both sides of the family, and ethnic background (eg Ashkenazi Jewish). Type of cancer and age of onset of affected relatives should be recorded where available.

In men with a family history of prostate cancer, take a family history of other cancers to assess the risk of having a pathogenic BRCA1 or BRCA2 variant. In the absence of a positive breast or ovarian cancer family history, BRCA1 and BRCA2 testing is generally not warranted.

Genetic testing

Family cancer clinics will assess individual risk to determine the utility of genetic assessment for BRCA1 or BRCA2 gene variants. BRCA1 and BRCA2 testing is also being used in men with prostate cancer to inform selection of treatment. As new genes in which variants predispose to prostate cancer are identified, testing of these new genes may be offered as part of a panel of genetic tests through the family cancer clinic.

There are validated polygenic risk scores for prostate cancer, including those that predict risk of aggressive disease. Their precise role in risk-based prostate cancer prevention and screening in Australia is yet to be determined.

When should I refer?

Refer men to a family cancer clinic if they have:

  • a family history suggestive of a BRCA1 or BRCA2 pathogenic gene variant
  • three first-degree or second-degree relatives with prostate cancer
  • two first-degree or second-degree relatives with prostate cancer, one of whom was diagnosed <50 years of age

Other considerations

Individuals at increased risk of prostate cancer should be encouraged to:

  • discuss their family history with all first-degree relatives
  • advise family members to discuss their risk with their general practitioner (GP).

Recommendations for PSA testing vary according to family history of prostate cancer:

Number of relatives with prostate cancer

Relative risk

Testing recommendations*

Father or one brother


PSA testing every two years for those aged 45–69 years

Father and two or more brothers


PSA testing every two years for those aged 40–69 years

*After discussion of benefits and harms of PSA testing. If PSA result is greater than 95th percentile for age, offer further investigation and referral to urologist

Further reading

  • The Royal Australian College of General Practitioners Guidelines for preventive activities in general practice. 9th edn. Melbourne, RACGP, 2016. Available at [Accessed 6 September 2022].
  • Prostate Cancer Foundation of Australia and Cancer Council Australia PSA Testing Guidelines Expert Advisory Clinical practice guidelines PSA testing and early management of test-detected prostate cancer. Sydney: Cancer Council Australia, 2015. Available at [Accessed 6 September 2022].
  • Jun Tu Zhen BS,Jamil Syed BS,Kevin Anh Nguyen BS, MS,Michael S. Leapman MD,Neeraj Agarwal MD,Karina Brierley MS,Xavier Llor MD,Erin Hofstatter MD,Brian Such. Genetic testing for hereditary prostate cancer: Current status and limitations. Cancer 2018.
  • Rohith Arcot, MDa,*, Todd M. Morgan, MDb, Thomas J. Polascik. Genetically Informed Prostate Cancer Screening. Urol Clin N Am 48 (2021) 373–386
  • National Cancer Institute (US). Genetics of prostate cancer (PDQ) – Health professional Bethesda, MD: National Institutes of Health, 2017. [Accessed 1 March 2022].
  • National Cancer Institute (US). BRCA1 and BRCA2: Cancer risk and genetic Bethesda, MD: National Institutes of Health, 2017. [Accessed 1 March 2022].

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