Hereditary cancer syndromes and genetic referral

Synopsis

Recognise patterns of inherited cancer predisposition, take and verify a three-generation pedigree, refer through genomic services, and manage testing, surveillance and family communication without acting on uncertain variants.

• Most cancers are not caused by a single inherited high-penetrance variant, but age, tumour pattern and family history can identify people who need genomic assessment.
• Referral clues include unusually young cancer, multiple primaries, bilateral disease, characteristic rare tumours and several related cancers on one side of a family.
• Take a three-generation pedigree with cancer site, age at diagnosis, ancestry where relevant and results of any previous testing; verify pathology when major decisions depend on it.
• Test an affected relative first when possible because a negative result in an unaffected person may be uninformative.
• A pathogenic or likely pathogenic germline variant can guide surveillance, risk-reducing options, targeted treatment and predictive testing of adult relatives.
• A variant of uncertain significance is not a diagnosis and must not drive prophylactic surgery or predictive family testing.
• Consent covers possible results, limitations, family implications, data use, reproductive choices and the possibility of unexpected information.
• People without an identified variant may still warrant enhanced surveillance when their verified family history remains strongly suggestive.