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CDKN2A – risk management

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Familial melanoma due to a heritable pathogenic variant in the CDKN2A gene is an autosomal dominant condition, strongly modified by polygenic and environmental risk factors.

This risk management guideline has been developed for individuals who have NOT been diagnosed with a relevant cancer/tumour. The care of affected individuals should be individualised based on their clinical situation, and the monitoring they need as part of their treatment and post-treatment follow up. However, management of the risk of new primary melanoma is in most cases their most important ongoing melanoma-related health issue.

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 carrier of a pathogenic variant in the CDKN2A gene. 
  • 50% risk of being a pathogenic variant carrier.

Exclusion criteria

  • Individuals in families with a pathogenic variant in other cancer predisposition genes associated with increased risks of melanoma. 
  • Individuals from families meeting familial melanoma diagnostic criteria where testing has not been done or where no pathogenic variant has been identified (see familial melanoma referral criteria)
Cancer/tumour type CDKN2A pathogenic variant carrier General population by age 80 yrs* 
Melanoma 52% by age 80 yrsr 5.1%**
Pancreatic Uncertain but increased in some populations rr 1.2%

*Source: Australian Institute of Health and Welfare (AIHW) 2020 Cancer Data in Australia; Canberra: AIHW. <https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/>. (2016 data)
**In Australia population melanoma risk varies by state (higher in QLD and WA).

The choice of risk management strategy should take into account current age, other health issues and residual cancer risk.

Cancer/tumour type Recommendations***
Melanoma
Surveillance Age Strategy and frequency

From 18 years of age
  • Monthly self examination of skin
  • Initial fundoscopy to exclude coincidental uveal naevi
  • 6 monthly specialist dermatological total body skin examination, including scalp and genitalia, supported by total body dermoscopy and total body photography
Pancreatic Surveillance Lack of evidence of benefit from screening. Should be undertaken only as part of a clinical trial^

 *** The impact of lifestyle on general cancer risks should be discussed e.g. exercise regularly, maintain a healthy weight, have a healthy diet, limit alcohol intake, do not smoke and avoid excessive sun exposure.
^Refer to Australian Pancreatic Cancer Genome Initiative website for up-to-date screening trials. Link in Website resources section.

Follow population guidelines to avoid excessive sun exposure and sunburn, including:
  • wear protective clothing when UV levels high (UV index ≥ 3)
  • use sunscreen that provides UVA and UVB protection and has a SPF of 30 or greater (UV index ≥ 3)
  • avoid vitamin D deficiency
  • solariums (tanning beds) should not be used 
  • do not smoke

See also Cancer Council Australia SunSmart Position statements

Several observational studies have demonstrated lower Breslow depth and lower risk of advanced or fatal melanoma in screen detected melanomas using either monthly self-examination or regular clinical examination of skin. Specificity of screening is higher with clinical rather than self-examination and improves with increased clinician training. A recent German study reported a 47% decrease in melanoma mortality in a screened population at average risk.r

Australian studies have shown that six-monthly specialist skin examination, supported by dermoscopy and total body photography, is effective in reducing thickness of prospectively detected melanomas, and in reducing the number of ineffectual skin lesion excisions in those at very high risk of melanoma (CDKN2A pathogenic variant carriers or equivalent).r The intervention was also cost-effective compared with current practice.r

Not smoking is recommended because pancreatic cancer has a known association with smoking and there are reports of an increased risk of smoking-related head-and-neck cancers in CDKN2A pathogenic variant positive families.r

Sixth monthly surveillance is recommended for CDKN2A pathogenic variant carriers because of evidence of cost effectiveness in the Australian setting.r 

Relatives who are non-carriers of an identified familial CDKN2A pathogenic variant have a higher risk of cutaneous melanoma than the general population (but lower than carrier relatives). This is probably explained by inheritance of other less penetrant melanoma susceptibility genes combined with shared environmental risks among family members. Less frequent (annual) melanoma surveillance may still be warranted for non-carrier relatives. (Link to Alfred Health - Melanoma risk calculator for health professionals. Link to QIMR Berghofer - Melanoma Risk Predictor)

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 and a dermatologist for comprehensive melanoma risk assessment. 

Informing family members about hereditary cancer

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Version 4

Date Summary of changes
4/10/2019

Protocol reviewed at May 2019 reference committee meeting. Discussions continued over email. Protocol approved for publication with the following changes made:

  • Summary: updated
  • Lifetime risk of cancer table: general population data updated
  • Cancer risk management guidelines: recommendations updated to align with recent data/publications
  • Evidence for risk management guidelines: updated to align with recent data/publications. Link to melanoma risk calculators added
  • References: new references added
  • New template changes applied
  • "Mutation" changed to "pathogenic variant" throughout document for consistency among eviQ cancer genetics protocols per agreement among the cancer genetics reference committees' chairs. Definition of "pathogenic variant" added as a pop-up.

Protocol version number increased to V.4. Review in 2 years
18/12/2020 The following sections of the protocol were updated to align with the revised eviQ cancer genetics risk management template:
  • Lifetime risk of cancer table:
    • Heading changed to "Lifetime risk of cancer/tumour"
    • Risk for general population updated to include AIHW 2016 data
  • Cancer risk management guidelines:
    • Heading changed to "Cancer/tumour risk management guidelines"
    • Sentence added above table "The choice of risk management strategy should take current age, other health issues and residual cancer risk into account" 
    • Surveillance: "Age to begin" changed to "Age"
  • Support and information: template wording updated.
04/08/2021

The following changes were made to align with ID 656 BRCA1 or BRCA2 – risk management (male):

  • Cancer risk management guidelines:
    • Pancreatic - Surveillance: "There is no evidence to support a benefit from screening. Screening should only be undertaken as part of a clinical trial." changed to "Lack of evidence of benefit from screening. Should be undertaken only as part of a clinical trial".
    • Footnote added "Refer to Australian Pancreatic Cancer Genome Initiative website for up-to-date screening trials. Link in Website resources section."
  • Website resources:
    • Added link to Australian Pancreatic Cancer Genome Initiative website

Version 3

Date Summary of changes
30/11/2016

New protocol discussed at October 2015 and March 2016 cancer genetics reference committee meeting. Approved and published on eviQ. Next review in 2 years.
31/05/2017 Transferred to new eviQ website. Version changed to V.2.
28/08/2019 Protocol title changed from 'Risk management for a CDKN2A mutation carrier' to 'CDKN2A – risk management' in accordance with Cancer Genetics Reference Committees' consensus. Version number increased to V.3.

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/1516

10 Aug 2022