Germline multigene panel testing for colorectal cancer: a systematic review and meta-analysis.
Alessandro Mannucci, Marta Puzzono, Giuseppe Marzocca et al.
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In 30 seconds
This systematic review and random-effects meta-analysis assessed germline multigene panel testing in unselected patients with colorectal cancer, pooling evidence from 21 eligible studies. Across 6925 individuals, 15·2% had at least one pathogenic or likely pathogenic variant; 7·9% had a high-penetrance variant and 5·4% a high-penetrance colorectal cancer predisposition variant. Yield was higher in early-onset than late-onset disease, but high-penetrance variant yield remained above 5% up to age 67 years. The authors conclude that these findings provide a benchmark for further study of universal testing.
Key findings
- Any pathogenic or likely pathogenic variant was found in 15·2% of patients overall (1061/6925; 95% CI 12·8-18·1).
- High-penetrance colorectal cancer predisposition variants were identified in 12·2% of early-onset and 3·8% of late-onset cases.
- High-penetrance variant yield remained greater than 5% up to age 67 years (95% CI 59-75).
- Greater first-degree family history prevalence correlated with higher overall and colorectal cancer-specific variant yields, but not non-colorectal variant yields.
Why it matters
The findings indicate that germline panel testing can identify clinically relevant inherited variants in a substantial proportion of patients, including those diagnosed at older ages. This may inform evaluation of inherited cancer risk and provide evidence for assessing broader testing strategies. However, the pooled estimates vary considerably across studies, and the analysis establishes diagnostic yield rather than the effects of testing on patient outcomes.
What to keep in mind
Heterogeneity was high across pooled estimates (I 2 =84·1% for any variant overall), and the evidence came from observational study designs and clinic-based series rather than randomised trials.