Uptake of cascade testing and the factors affecting its implementation among patients in Japan with Lynch syndrome

In the clinical management of hereditary cancer syndromes, risk assessment is needed not only for affected patients but also for their blood relatives. In the families of Lynch syndrome (LS) patients, cascade testing is performed to identify those who carry germline pathogenic variants (GPVs) of mismatch repair genes and to enable the clinical surveillance of cancer-prone organs in relatives with GPVs. To date, the uptake of cascade testing has not been fully reported, and only a limited number of studies have analyzed barriers to its implementation. This retrospective study analyzed the uptake of cascade testing in relatives of Japanese LS probands and clarified factors that promote it. The study included 56 LS probands and 162 first-degree relatives (FDRs). Clinicodemographic data were collected from medical records, and univariate and multivariate analyses compared those who did and did not undergo cascade testing. Fifty-two (32.1%) FDRs of LS probands underwent cascade testing. Independent predictors of cascade testing uptake were the attendance of a family member at the proband's genetic counseling session (odds ratio [OR]: 3.6), female sex of the proband (OR: 2.9), and female sex (OR: 2.2). The cascade testing uptake in this study was comparable to or lower than rates reported in other countries. Encouraging family members to attend genetic counseling with the proband may improve cascade testing uptake in LS families. Further prospective studies are needed to clarify the reasons for accepting or declining cascade testing, including an evaluation of intrafamilial communication processes.