Patients with VUS and patients with negative results were similarly likely to have a change in their clinical management (OR 1.41, P = 0.182), and less likely to have a change in management than patients with positive results (OR 0.09, P < 0.0001). Patients with VUS reported higher genetic test-specific concerns on the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale than patients with negative results (mean difference 3.73 P = 0.0126), and lower than patients with positive results (mean difference -7.01, P = 0.0014). The search identified 4539 unique studies and 15 were included in the review.
Data were synthesized through meta-analysis and meta-aggregation. Two reviewers screened studies and extracted data. This study systematically reviewed and synthesized the literature on psychological and clinical outcomes of receiving a variant of uncertain significance (VUS) from multigene panel testing or genomic sequencing. Findings also provide direction for future work that can further explicate the impact of receiving a VUS. These results provide insight into the ways healthcare providers can support patients who receive VUS for Lynch syndrome. The majority of participants were unaware of the possibility of a VUS before receiving their result and expected reclassification over time. Mobilizing strategies to reduce their risk included vigilant cancer surveillance, information seeking and notifying relatives. Half of the participants appraised their variant as a danger and implemented coping strategies to reduce the threat of developing cancer. Most individuals recalled their result and perceived various types of uncertainty associated with their VUS. The interviews were transcribed and analyzed. Semi-structured interviews were conducted with 27 adult individuals who received a VUS for Lynch syndrome mismatch repair genes between 20.
This descriptive study uses Mishel’s theory of uncertainty in illness to explore the experience of individuals who have received a VUS as part of the genetic testing process. A VUS introduces new counseling dilemmas for the understanding and psychosocial impact of uncertain genetic test results. Providers and patients encounter challenges related to the management of Variants of Unknown Significance (VUS).
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