A Lancet Oncology policy review, building on the journal's commission on cancer genomics, examines the spread of cancer susceptibility testing from genetics clinics into routine oncology and population programmes.
The authors draw a clear line. For a small set of first-wave genes, including BRCA1, BRCA2, MLH1 and MSH2, cancer risks are well characterised and the downstream interventions are supported by substantial observational evidence, though not randomised trials. For many genes added later to multigene panels, penetrance is uncertain, variant-level risk is poorly defined, and there is little or no evidence that the recommended surveillance or surgery reduces mortality or is cost-effective. Polygenic risk scores discriminate only modestly and perform differently by ancestry.
They propose a tiered approach: testing where net benefit is shown, restricted or selective testing elsewhere, and research-only use for the least established genes and scores. For oncologists ordering panels, the practical point is that a result in a lower-evidence gene should not drive the same intensity of intervention as a BRCA or Lynch result.
- Act on pathogenic variants in BRCA1, BRCA2 and the Lynch genes according to established guidance.
- Interpret results in less-established panel genes cautiously, with genetics input before major interventions.
- Do not use polygenic risk scores to guide individual surveillance outside research, especially in non-European ancestry.
- Explain uncertainty to patients before ordering broad panels, including the chance of variants of uncertain significance.
Why it matters
Broad panels now generate results that the evidence cannot yet translate into safe intervention.
Don't overread it
This is a policy review, not new data; it does not change established guidance for first-wave genes.
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