Cascade Genetic Testing Among Relatives at Risk for Lynch Syndrome: A Systematic Review and Meta-Analysis

This is a systematic review and meta-analysis to evaluate the uptake of cascade genetic counseling and testing within families with Lynch syndrome. Our goal was to provide a more current estimate of testing rates specific to this population to inform future efforts aimed at improving the identification of individuals with Lynch syndrome.

This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was preregistered with PROSPERO (registration No.: CRD42024542006). A comprehensive literature search was conducted on electronic databases. Data from eligible studies were meta-analyzed to determine uptake rates of cascade genetic counseling and testing within families with Lynch syndrome.

Across all 18 studies included in the meta-analysis, there was a total of 4,939 probands, and 10,461 relatives were used in the evaluation of the uptake rate of cascade genetic testing. Eight of these studies reported on the uptake of genetic counseling for cascade testing, with 42% (95% CI, 18 to 67) of relatives engaging in counseling. Across the 18 studies in the meta-analysis, the overall uptake of cascade genetic testing was 46% (95% CI, 32 to 60), with higher uptake among female compared with male relatives, and among first-degree compared with second-degree relatives.

The utilization of cascade genetic testing among people at risk for Lynch syndrome remains suboptimal, particularly among male relatives and more distant relatives. Targeted interventions are urgently needed to improve equitable uptake rates of cascade genetic testing among relatives at risk for Lynch syndrome.