Association between proband characteristics and CDH1 cascade genetic testing uptake in at-risk relatives

Abstract

Cascade genetic testing involves testing at-risk relatives for a gene variant identified in the family to tailor clinical management. The first person in a family identified with a pathogenic or likely pathogenic variant is the proband. We aimed to determine proband characteristics associated with cascade testing for the CDH1 gastric and breast cancer susceptibility gene. Cascade genetic testing proportions in 100 CDH1 families were analyzed. Overall, 57% (248/427) of proband's first-degree relatives (FDR) and 31% (135/436) of second-degree relatives (SDR) underwent testing. Proband characteristics associated with higher mean proportions of genetic testing in FDR included male sex (p = 0.03) and personal history of gastric cancer (p = 0.05). A difference was also detected in mean uptake proportions by proband's race/ethnicity. White probands had higher mean proportions of SDR tested (40%) compared to Asian (9%, p = 0.02) and Black (5%, p = 0.001) probands. Testing proportions in FDR and SDR increased with the length of time from proband's CDH1 diagnosis (FDR p < 0.001, SDR p = 0.002). Age when proband was tested, personal history of breast cancer, and variant in another cancer gene did not influence testing uptake in FDR and SDR. Proband characteristics associated with higher CDH1 cascade genetic testing proportions include male sex, White race/ethnicity, and a personal history of gastric cancer. Probands who are female, Asian, Black, and those without a personal history of gastric cancer may require tailored support facilitating CDH1 cascade testing in at-risk relatives. Additional studies are needed to gain a deeper understanding of how proband characteristics influence the uptake of cascade genetic testing for cancer risk.