Synopsis
Identify inherited colorectal cancer risk, interpret tumour and germline testing in sequence, and connect patients and relatives to gene-specific surveillance, prevention and surgical planning.
- Lynch syndrome is usually autosomal dominant and caused by a germline pathogenic variant affecting MLH1, MSH2, MSH6, PMS2 or EPCAM-mediated MSH2 silencing; it produces cancer predisposition without carpeting polyposis.
- Familial adenomatous polyposis is an autosomal dominant APC-associated syndrome with tens to thousands of adenomas and near-inevitable colorectal cancer without effective surveillance and prophylactic surgery.
- MUTYH-associated polyposis is autosomal recessive; biallelic carriers have important colorectal risk, while risk and management for a single variant differ and require contextual genetics advice.
Key red flags
Hundreds to thousands of colorectal adenomas developing from adolescence, often with an APC pathogenic variant and extracolonic features, require registry surveillance and planned prophylactic colorectal surgery.
Investigation priorities
Estimate inherited probability and identify the most informative affected relative and syndrome-specific cancers or polyps.
Management branches
A person is newly diagnosed with colorectal cancer at any age.
- Order or verify four-protein MMR immunohistochemistry or MSI testing and record responsibility for acting on the result without delaying staging or cancer treatment.
- For abnormal MLH1, follow the NICE BRAF V600E then MLH1 promoter-methylation sequence; for other abnormal loss patterns, progress to appropriately counselled germline testing.
Key medicines
Aspirin chemoprevention in Lynch syndromeNICE advises considering daily aspirin for more than two years; select the actual dose through shared specialist decision using current guidance and individual risk.
Bowel-cleansing preparationUse a split-dose local regimen timed for high-quality surveillance, modified for age, renal or cardiac disease, constipation burden and the selected endoscopy list.