Colorectal cancer (high risk) – risk management

The main risk factors for colorectal cancer (CRC) are increasing age and family history. Less than 1% of the population are at high risk of CRC based on their family history once the confirmed high risk CRC predisposition syndromes (e.g. Lynch syndrome, familial adenomatous polyposis (FAP), juvenile polyposis) have been excluded. Family history does not necessarily imply an inherited monogenic cause. Most people in this risk group will not develop CRC, but the risk of CRC is approximately seven to ten-fold higher than average. Approximately 30–40% of people in this group will develop CRC in their lifetime.^r

Unaffected individuals who are at high risk of colorectal cancer (CRC) based on their family history,^*# including those with:

• three or more first-degree or second-degree relatives with CRC, with at least one diagnosed before age 55 years^#
• three or more first-degree relatives with CRC diagnosed at any age^#

* Risk category by CRC family history from Cancer Council Australia^r 
# on same or different sides of the family

Exclusion criteria

• Individuals who have had CRC.
• Member of a family where an inherited cancer syndrome associated with a predisposition to CRC is suspected or confirmed.
• Individual at moderately increased risk of CRC based on family history - see Colorectal cancer (moderately increased risk) – risk management.
• Individual with inflammatory bowel disease or documented colorectal polyps.

Cancer/tumour type	Individuals at high risk of CRC by age 75 years	General population risk by age 75 years*
Colorectal**	30–40%**r	3.7%

* Source: Australian Institute of Health and Welfare (AIHW) 2021 Cancer Data in Australia; Canberra: AIHW. <https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-risk-data-visualisation>. (2017 data)
** This data does not take into account the impact of surveillance.

Colorectal

Surveillance

Insufficient evidence regarding the optimal screening strategy for this population means that a number of published screening recommendations exist differing in the definition of risk, type and frequency of tests recommended, and the age at which individuals should start screening.

For people in this category, their risk of colorectal cancer (CRC) is as high at age 35 years as that of the average population at age 50 years, which is about 1%. This would justify biennial screening with iFOBT from age 35 to 44 years. By age 45 years, their risk is above 4%, which is sufficiently high to warrant colonoscopy every 5 years from 45 to 74 years.^r There have been no studies conducted to determine the utility of beginning screening 10 years before the earliest diagnosis in the family, which was a recommendation in previous guidelines.^r

Risk-reducing medication

There have been no trials of CRC prevention for this risk category. Considerable evidence supports the effectiveness of aspirin as risk-reducing medication for CRC in patients with Lynch syndrome.^r

Randomised controlled trials were reviewed by Cancer Council Australia and this led to the guarded conclusion that aspirin is effective in the primary prevention of CRC. After taking into account the observational epidemiological data and other potential benefits, the revised guidelines have made a strong recommendation to consider universal aspirin chemoprevention except where contraindicated, especially for those with excess cardiovascular risk.^r Thus it has been included in these guidelines for those at high risk. 

Modifiable lifestyle risk factors for colorectal cancer

For a summary of the evidence for modifiable lifestyle risk factors for CRC, see Cancer Council Australia: Colorectal Cancer Guidelines Working Party. Clinical practice guidelines for the prevention, early detection and management of colorectal cancer. These recommendations apply to the general population; there is no specific evidence for the high-risk group.

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Version 7

Date	Summary of changes
15/09/2023	New eviQ cancer genetics risk management template changes applied - PDF of changes. Version number changed to V.7.

Version 6

Date	Summary of changes
13/02/2023	The following sections of the document were updated to align with the new eviQ cancer genetics risk management template: Summary: Template sentence updated. Cancer/tumour risk management guidelines: Template sentence updated. Lifestyle factors sentence moved above table. Version number increased to V.6.

Version 5

Date	Summary of changes
07/02/2022	Document reviewed by cancer genetics reference committee out of session on MS Teams. Approved for publication with the following changes made: Summary: minor wording changes. Third paragraph (template sentence) removed.  Target group: Bullet 2: 'all diagnosed at ≥55 years' changed to 'diagnosed at any age' Bullet 3: 'Other family histories...' removed from criteria Other minor wording changes Footnote ' Risk category by CRC family history...' moved up to below inclusion criteria Lifetime risk of cancer: General population risk updated to AIHW 2017 data References: updated reference for CAPP2 study added Version increased to V.7. Review in 2 years.

Version 4

Date	Summary of changes
20/12/2019	"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.4.
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 into account current age, other health issues and residual cancer risk."  Surveillance: "Age to begin" changed to "Age".

Version 3

Date	Summary of changes
29/03/2019	New protocol developed after discussions at Nov 2018 reference committee meeting. Discussion continued over email and protocol approved for publication. Version V.1. To be reviewed in 2 years.
11/06/2019	Cancer risk management guidelines section: Colorectal - risk reducing medication: Recommendation updated to actively consider low-dose aspirin from commencement of colonoscopy screening. Version changed to V.2. as update to protocol signals practice change. Review date kept same.
28/08/2019	Protocol title changed from 'Risk management for individuals at high risk of colorectal cancer (excluding known hereditary bowel cancer syndromes)' to 'Colorectal cancer (high risk) – risk management' in accordance with Cancer Genetics Reference Committees' consensus. Version number increased to V.3.