Genomics in general practice

Disease specific topics

Familial colorectal cancer

Familial colorectal cancer


A comprehensive family history must be taken and regularly updated to identify patients who may be at risk of familial colorectal cancer (CRC). 

Refer individuals and families who meet high-risk criteria to a family cancer clinic. 

Individuals at average or only slightly higher risk do not require a colonoscopy, and should be encouraged to participate in the National Bowel Cancer Screening Program (ie faecal occult blood test [FOBT]).

What do I need to know?

Highly penetrant gene variants Penetrance refers to the proportion of people with a particular genetic variant who will go on to develop the condition. For example, people carrying an autosomal dominant variant may not always develop the condition – this is called ‘incomplete penetrance’. If a condition is 100% penetrant, an individual will definitely develop the condition. If penetrance is 80%, most but not all individuals will develop the condition. Other genes and lifestyle factors, such as diet, exercise and smoker status, may affect the penetrance of some conditions. For more information, refer to MedlinePlus’ ‘What are reduced penetrance and variable expressivity?’ in several genes are associated with specific familial CRC syndromes:

  • Lynch syndrome (associated with a range of cancers, including colorectal, endometrial, ovarian, gastric, renal pelvis, ureter, small bowel, biliary tract, brain) is caused by dominantly inherited pathogenic variants in the MLH1, MSH2, MSH6 or PMS2 These genes encode mismatch repair proteins. Lynch syndrome accounts for up to 6% of all colorectal cancer.
  • Familial adenomatous polyposis (FAP), associated with multiple adenomas in the large bowel, is caused by dominantly inherited pathogenic variants in the APC FAP accounts for approximately 1% of colorectal cancer cases.
  • There are other rare inherited CRC syndromes that may be associated with specific polyp pathologies, phenotypic features or other cancer types in a family

Features within a family that are suggestive of increased risk of having a pathogenic variant for Lynch syndrome or FAP include:

  • multiple affected relatives on the same side of the family
  • multiple CRCs in the same person (be they synchronous (occurring at the same time) or metachronous (occurring at different times))
  • CRC diagnosed <50 years of age
  • immunohistochemistry in a CRC showing absent staining for one or more mismatch repair proteins
  • other Lynch–syndrome related cancers (as above)
  • >20 adenomas in the large bowel
  • adenomas diagnosed <30 years of age

A three-generation family history is key to identifying high-risk families who are most likely to benefit from genetic testing. Such a history should include first-degree and second-degree relatives on both sides of the family. Type of cancer (including whether the cancer is metachronous) and age of onset should be recorded where available.

Use existing risk criteria to identify families at increased risk of an inherited CRC syndrome (high risk), or individuals who may require additional screening or chemoprevention.

Genetic testing

Family cancer clinics will assess individual risk to determine the utility of genetic testing for Lynch syndrome or FAP. As new genes in which pathogenic variants predispose to CRC are identified, testing of these new genes may be offered as part of a panel of genetic tests through family cancer clinics.

Validated polygenic risk scores for CRC are commercially available. In combination with other known risk factors (e.g. family history and lifestyle risks) PRS may be used to provide individualised information about CRC risk. Their precise role in risk-based CRC prevention and screening in Australia is yet to be determined

When should I refer?

The recommended CRC screening strategy and different individual risk categories are outlined in The Royal Australian College of General Practitioners’ (RACGP’s) 2016 Guidelines for preventive activities in general practice (Red Book) and The Cancer Council Australian Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer.

Other considerations

Individuals at increased risk for CRC should be encouraged to:Edit Link

  • discuss their family history with all first-degree relatives
  • advise family members to discuss their risk with their general practitioners (GP).

Further reading

  • The Royal Australian College of General Guidelines for preventive activities in general practice. 9th edn. East Melbourne, RACGP, 2016. [Accessed 6 September 2022].
  • Cancer Council Australian Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer.
  • Jenkins MA, Ait Ouakrim D, Boussioutas A, Hopper JL, Ee HC, Emery JD, Macrae FA, Chetcuti A, Wuellner L, St John DJB. Revised Australian national guidelines for colorectal cancer screening: family history (2018) Med J Aust. 2018;209(10):455-460.
  • Samadder NJ, Jasperson K, Burt Hereditary and common familial colorectal cancer: Evidence for colorectal screening. Dig Dis Sci 2015;60(3):734–47.
  • Rubenstein JH, Enns R, Heidelbaugh J, Barkun American Gastroenterological Association Institute guideline on the diagnosis and management of Lynch syndrome. Gastroenterology 2015;149(3):777–82.

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