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HOXB13 (G84E) – risk management (male)

In this document the terms ‘male’ and ‘female’ refer to sex assigned at birth. For more information about providing individualised care refer to Resources to assist in the care of transgender individuals referred to a clinical genetics service or familial cancer centre

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Familial prostate cancer predisposition due to a heritable pathogenic variant in the HOXB13 gene is an autosomal dominant condition.

The care of an individual who has developed a related tumour or cancer should be individualised based on their clinical situation, their family history and the monitoring they need as part of their treatment and post-treatment follow-up.

The risk management of an individual with a pathogenic variant in two or more genes that confer a predisposition to cancer should also be individualised.

  • Known or obligate male HOXB13 pathogenic variant carrier unaffected with cancer
  • Males at 50% risk of inheriting a HOXB13 pathogenic variant

Exclusion criteria

  • Known or obligate female HOXB13 pathogenic variant carrier
  • Individuals with a pathogenic variant in another prostate cancer predisposition gene 
  • Individuals with a variant of uncertain significance
Cancer/tumour Risk for this group by age 80 years General population risk by age 80 years
Prostate 33%r (95% CI 23-46%) 16.3%*

* Source: Australian Institute of Health and Welfare (AIHW) 2022 Cancer Data in Australia; Canberra: AIHW. <https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-risk-data-visualisation>. (2018 data, unadjusted for competing mortality)

The choice of risk management strategy should take into account current age, other health issues and age-related cancer risk. Risks and benefits of interventions should be discussed with an experienced medical professional.

The impact of lifestyle on cancer risk should be discussed e.g. exercise most days for at least 30 minutes at moderate or strenuous intensity, maintain a healthy weight, have a healthy diet, limit alcohol intake, do not smoke and avoid excessive sun exposure.

Cancer/tumour type Recommendations**
Prostate Surveillance
  • Consider annual PSA +/- digital rectal exam (DRE) from age 40 years
  • If persistent elevation of PSA above normal refer to a urologist
Risk-reducing medication No evidence

Prostate cancer

In the general population, surveillance can be associated with overdiagnosis and overtreatment with no evidence for improved short-term survival (10-year period). However, there is preliminary evidence for value in surveillance of individuals with BRCA pathogenic variantsr as data suggests that BRCA-related prostate cancer is aggressive with a higher probability of distant metastasis and occurs at a younger age than sporadic prostate cancer.r

Carriers of a HOXB13 G84E pathogenic variant are reported to have higher rates of young onset prostate cancer (diagnosed age 55 years and under)rr and have been shown to have prostate cancer risks comparable to carriers of a BRCA2 pathogenic variant (OR 3.88, 95% CI 2.85-5.24) in a large population-based cohort.r

The HOXB13 G84E pathogenic variant is prevalent in more than 1% of the Swedish population.r Founder variants in HOXB13 have been identified in individuals with prostate cancer in other ethnic subpopulations,rr however, these remain variants of uncertain significance at this time.

The risk of prostate cancer in individuals with a HOXB13 G84E pathogenic variant is modified by family history.rr

Other cancers

There is no demonstrable increase in breast cancer risk in carriers of the HOXB13 G84E pathogenic variant.r

First degree blood relatives (parents/brothers/sisters/children) are at up to 50% risk of having inherited the pathogenic variant. More distant relatives may also be at risk of inheriting the pathogenic variant. Genetic relatives should be referred to a clinical genetics service or familial cancer centre to discuss predictive genetic testing.

Informing family members about hereditary cancer

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Version 3

Date Summary of changes
15/09/2023

New eviQ cancer genetics risk management template changes applied - PDF of changes.

Version number changed to V.3.

Version 2

Date Summary of changes
19/04/2023

Protocol reviewed at October 2022 cancer genetics reference committee meeting. Approved for publication with the following changes made:

  • Protocol template changes applied throughout document
  • Minor wording changes made throughout document
  • Lifetime risk of cancer tumour: general population risk updated to AIHW 2018 data
  • Evidence for risk management guidelines: minor updates regarding variants of uncertain significance in other ethnic subpopulations.

Approved on 19/04/2023, published on eviQ on 02/05/2023. Version increased to V.2. Review in 2 years. 

Version 1

Date Summary of changes
12/08/2021 New protocol developed and discussed at May 2021 cancer genetics reference committee meeting. Approved for publication as V.1. Review in 1 year.

The information contained in this document is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to care or treatment. Any clinician seeking to apply or consult this document is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/4004

10 Sep 2024