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Amsterdam I families with active exclusion of a MMR defect

This document is a quick and concise evidence-based summary to provide additional information, instruction, or guidance to complement a treatment protocol or clinical resource document. 

Familial colorectal cancer syndrome X is a new term used to describe some families who fulfil the Amsterdam I clinical criteria but show normal mismatch repair (MMR) protein immunohistochemistry (IHC) and/or are MSI stable.r 

In these families, the reason that multiple family members are affected by colorectal cancer may be due either to pathogenic variants in other genes or they may represent a polygenic effect.

Risk estimate

Familial colorectal cancer syndrome X is associated with a lower incidence of extra-colonic tumours and a slower rate of malignant transformation compared to Lynch syndrome.rr

Risk management strategy for unaffected first-degree relatives

Data from the Colorectal Adenoma/Carcinoma Prevention Program (CAPP2) showed a significant reduction in the incidence of colorectal cancer and other Lynch syndrome-associated cancers for those taking aspirin. While there is limited evidence about optimal dose, a regular daily low dose (100-300mg) of aspirin could be considered.rr 

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Version 4

Date Summary of changes
13/08/2021

Document reviewed alongside ID 1410 at the August 2020 cancer genetics reference committee meeting. Discussion continued via email and MS Teams. Approved for publication with the following changes made: 

  • Heading changed from 'Amsterdam I or II families with active exclusion of a MMR defect' to  'Amsterdam I families with active exclusion of a MMR defect'
    • First sentence: '...families who fulfil the Amsterdam I or II Clinical Criteria but show no abrogation of the MMR pathway.' changed to 'families who fulfil the Amsterdam I clinical criteria but show normal mismatch repair protein (MMR) immunohistochemistry (IHC) and/or are MSI stable.'
    • Second sentence: 'cluster effect' changed to 'polygenic effect'
  • Risk estimate:
    • 'compared to Lynch syndrome.' added to end of sentence
  • Risk management strategy for unaffected first-degree relatives:
    • Heading changed from 'Risk management strategy' changed to 'Risk management strategy for unaffected first-degree relatives'
    • First bullet:
      • Removed '3 yearly colonoscopy commencing from age 40 or 10 years younger than the age of the youngest colorectal cancer diagnosis in the family (whichever occurs first) continuing at least until age 70.'
      • Added 'Risk management can be based on Cancer Council Australia Clinical Guidelines Network (wiki link) to individualise screening based on family history.'
    • New paragraph added: 'Data from the Colorectal Adenoma/Carcinoma Prevention Program (CAPP2) showed...'

Version number increased to V.4. Review in line with ID 1410.
16/04/2024 Document reviewed alongside ID 1410 at the October 2023 cancer genetics reference committee meeting. No changes made.

Version 3

Date Summary of changes
31/05/2017 Transferred to new eviQ website.  Version number changed to V.2.
Previous website  ACI ID: 53.
21/03/2018  Supporting documentation reviewed in accordance with ID 1410 - Risk management for lynch syndrome. Nil major changes made. 
06/09/2019 "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. 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/3158

19 Apr 2024