Hereditary colorectal cancer

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Patients with colorectal tumours showing mismatch-repair deficiency on universal pathology screening
• Individuals and families meeting the or Lynch syndrome
• Children, adolescents or young adults with several colorectal adenomas or early-onset colorectal cancer or if there is a clinical suspicion of a polyposis syndrome
• At-risk relatives of a person with a known germline pathogenic variant

Testing is typically requested by gastroenterologists, colorectal surgeons, oncologists, pathologists and clinical geneticists.

Genetic testing is used when a hereditary syndrome is suspected from tumour screening, family history or early-onset disease, and it guides treatment decisions. For example, comprehensive germline testing detected pathogenic variants in 15.5% of 361 unselected colorectal cancer patients.

A pathogenic or likely pathogenic variant establishes the specific molecular diagnosis, identifying the causative gene and condition. A variant of uncertain significance (VUS) is an unclear finding: current evidence is insufficient to classify it as likely benign or likely pathogenic, and reanalysis can be offered after a few years as evidence accumulates. In other cases, no pathogenic variant is detected in the analysed genes. The presence of a pathogenic variant cannot, however, be entirely excluded: the causative change may lie in a gene not yet linked to the condition, or in a regulatory region that current methods cannot reliably capture.

Each variant is classified according to ACMG/AMP criteria.

When a germline pathogenic variant is confirmed, risk-adapted surveillance, such as intensified colonoscopy, and risk-reducing surgical or pharmacological prevention can be established. Lynch syndrome additionally carries extracolonic cancer risks that warrant gynaecological and other organ surveillance. A confirmed familial variant enables cascade predictive testing of relatives, allowing carriers to enter surveillance and non-carriers to avoid unnecessary procedures.

Medical genetic counselling is an important part of the testing process. It helps patients and families understand the test, interpret results, and make well-informed medical decisions, and it supports physicians in delivering informed care. Availability of genetic counselling services may vary by country, so please contact us to check access in your region.

Testing uses next-generation sequencing (NGS) based multi-gene panels.

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