Germline multigene panel testing for colorectal cancer: a systematic review and meta-analysis

Pathogenic or likely pathogenic germline variants in cancer predisposition genes, assessed by next-generation sequencing multigene panels in unselected patients with colorectal cancer.

This PROSPERO-registered systematic review and meta-analysis pooled 21 studies reporting germline panels of at least five genes in unselected patients with colorectal cancer. Across 6,925 patients, the pooled prevalence of at least one pathogenic or likely pathogenic variant was 15.2% (95% CI 12.8-18.1), including 7.9% in high-penetrance genes and 5.4% in high-penetrance colorectal cancer predisposition genes. Yield was 17.7% below age 50 versus 13.0% at age 50 or older, with a progressive decline according to age at diagnosis. Yield for high-penetrance variants remained above 5% up to age 67 (95% CI 59-75); neither panel size nor publication year affected results in meta-regression.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The number that matters is the age threshold: 67, not 50, is the age below which high-penetrance yield still exceeds the thresholds usually accepted for offering testing. That is a direct quantitative argument against prescribing criteria based on early onset and family history, which remain the rule in most guidelines. Substantial heterogeneity (I² 73-93% across strata) and two of 21 studies at high risk of bias mean these bounds should be read as an order of magnitude rather than a precise estimate.

Analysis by Dr Thibaut Benquey