Psychological distress and cancer worry in unaffected relatives undergoing cascade testing with multigene panel testing

Multigene panel testing (MGPT) is increasingly used for diagnosing hereditary cancers; however, its application in cascade testing remains limited, and the psychological impact on unaffected relatives is not well understood. This multicenter study in Japan recruited 123 first-degree relatives without a personal history of cancer to evaluate psychological responses before (T0) and two weeks after (T1) MGPT result disclosure. Participants completed the Japanese version of the Cancer Worry Scale (CWS-J) at both time points and the Impact of Event Scale-Revised (IES-R) at T1. Two weeks after disclosure, 6.5% of relatives met the threshold for clinically significant distress. Mean IES-R scores were higher among carriers of pathogenic variants (mean 8.2) than among those with negative results (mean 4.8) or variants of uncertain significance (mean 2.4). In contrast, multivariate analysis revealed no independent association between test result and post-disclosure distress. In contrast, higher baseline CWS-J scores were strongly associated with elevated IES-R scores after disclosure (p < 0.001). Children and relatives who frequently discussed cancer risk within their families exhibited higher distress levels than other subgroups. Overall, CWS-J scores showed no significant change from pre- to post-disclosure, with 41% of relatives maintaining persistently high worry. Across both time points, unaffected relatives consistently reported lower CWS-J scores than individuals with cancer (p < 0.0001). These findings suggest that MGPT has minimal psychological impact on unaffected relatives undergoing cascade testing, although those with higher preexisting cancer worry may require additional psychosocial support.