Inherited colorectal cancer syndromes

Why screen patients for inherited colorectal cancer syndromes?

Colorectal cancer is the third most common type of newly diagnosed cancer in Australia. It is estimated that 30% of patients with colorectal cancer have a family history of the disease, and up to 10% have genomic variants associated with inherited cancer syndromes including Lynch syndrome and familial adenomatous syndromes FAP and MAP.

MBS rebated diagnostic and predictive testing for the genes associated with these syndromes is now available for patients who meet criteria and when requested by a specialist medical practitioner. Guidelines recommend anyone with a Lynch syndrome risk of ≥5% as calculated by risk prediction models have germline testing however, MBS guidelines require a risk of ≥10%.

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When is testing useful?

Detection of pathogenic variants in genes associated with inherited colorectal cancer syndromes:

•  confirms a diagnosis in patients with a personal history of cancer

•  provides genotype-specific information on lifetime risk of cancers

•  directs patient management, including surveillance and consideration of prophylactic surgery, based on genotype-specific risks

•  guides testing of at-risk (asymptomatic) family members

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Our panels

Lynch syndrome is one of the most common cancer predisposition syndromes, and confers a significantly increased lifetime risk of colorectal cancer, endometrial cancer and multiple other cancers. A diagnosis of Lynch Syndrome is confirmed by the detection of a pathogenic germline variant in one of the MMR genes (MLH1, MSH2, MSH6 and PMS2) or the EPCAM gene. These are found in our Lynch syndrome panel.

Familial adenomatous polyposis is an autosomal dominant disorder characterised by numerous (>100 to 1000s) gastrointestinal adenomatous polyps that almost inevitably progress to CRC by age 40. A variant of the disorder, attenuated FAP, has a later onset, fewer polyps (usually <100) and reduced occurrence of extra-intestinal manifestations. Both forms of FAP are caused by pathogenic variants of the APC gene. Up to one third of cases are due to de novo (new) variants and therefore have no family history of disease.

MUTYH-associated polyposis is an autosomal recessive disorder characterized by attenuated adenomatous colorectal polyposis (usually 15-100 polyps) and significantly increased lifetime risk of colorectal cancer. MAP is caused by biallelic pathogenic variants of the MUTYH gene.

The APC and MUTYH genes are both found in our FAP/MAP panel.

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