Genomics in general practice

Familial prostate cancer

Last revised: 30 Nov 2018

Practice point

A comprehensive family history must be taken and regularly updated to identify patients who may be at risk of familial prostate cancer.1

Use existing risk criteria to identify individuals who are at increased risk of carrying a pathogenic variant 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.2
 

Approximately 1–2% of prostate cancer is due to pathogenic variants in the BRCA1 and BRCA2 genes. These show an autosomal dominant inheritance pattern.3

Multiple genetic and environmental factors are likely to influence the risk of prostate cancer. Genetic testing for gene variants in men with multiple cases of prostate cancer only in their family is not widely available.

Features suggestive of increased risk of carrying a pathogenic BRCA1 or BRCA2 variant genes 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:4,5

  • 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 (eg metachronous) 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 carrying a pathogenic BRCA1 or BRCA2 variant genes. In the absence of a positive breast or ovarian cancer family history, BRCA1 and BRCA2 testing is generally not warranted.

Family cancer clinics will assess individual risk to determine the utility of genetic assessment for BRCA1 or BRCA2 gene variants. As new genetic variants predisposing to prostate cancer are identified, these new variants may be offered as part of a panel of genetic tests through the family cancer clinic.

There is currently no role in general practice for ordering a cancer-risk assessment based on a single nucleotide polymorphism (SNP) profile (genotyping).

Refer men to a family cancer clinic if they have:1,4

  • 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.

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:2

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