Lynch Syndrome Limbo: Patient Understanding of Variants of Uncertain Significance

Abstract

Providers and patients encounter challenges related to the management of Variants of Unknown Significance (VUS). A VUS introduces new counseling dilemmas for the understanding and psychosocial impact of uncertain genetic test results. 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. Semi-structured interviews were conducted with 27 adult individuals who received a VUS for Lynch syndrome mismatch repair genes between 2002 and 2013. The interviews were transcribed and analyzed. Most individuals recalled their result and perceived various types of uncertainty associated with their VUS. Half of the participants appraised their variant as a danger and implemented coping strategies to reduce the threat of developing cancer. Mobilizing strategies to reduce their risk included vigilant cancer surveillance, information seeking and notifying relatives. The majority of participants were unaware of the possibility of a VUS before receiving their result and expected reclassification over time. These results provide insight into the ways healthcare providers can support patients who receive VUS for Lynch syndrome. Findings also provide direction for future work that can further explicate the impact of receiving a VUS.

Patient goals, motivations, and attitudes in a patient‐driven variant reclassification study

“…They may have been unwilling to let go of their VUS classification as an emotional and clinical crutch, leading to a subconscious but intentional misunderstanding of their results. These findings overlap with findings from Skinner et al () and Solomon et al (). Skinner et al () described one participant that interpreted her VUS from exome sequencing as a definitive molecular diagnosis for her family history despite receiving clinical counseling on the uncertainty of the diagnosis, while Solomon et al () identified aggressive screening as a coping mechanism for uncertainty in patients who received a VUS for Lynch syndrome genes.…”

“…They may have been unwilling to let go of their VUS classification as an emotional and clinical crutch, leading to a subconscious but intentional misunderstanding of their results. These findings overlap with findings from Skinner et al (2017) and Solomon et al (2017). Skinner et al (2017)…”

“…Solomon et al () also described how uncertainty contributed to perception of VUS results and drove other coping strategies for individuals receiving VUS in Lynch syndrome genes. In addition to advocating for more aggressive screening, coping strategies included reaching out to family members at risk of inheriting the variant, seeking information through the patient's own internet research, having faith in eventual reclassification, and feeling self‐empowered to reduce current health risks.…”

Patients' perspectives of variants of uncertain significance and strategies for uncertainty management

“…However, unintentionally giving the impression that re‐contact, in the event of VUS reclassification, is contingent on research participation is problematic as research participation should not be coerced. Although not reported by our study participants, it is possible that participation in VUS reclassification studies would also aid uncertainty management for patients as has been suggested previously (Solomon et al, ). Providers could assist patients with other methods of uncertainty management—such as learning strategies to cope with uncertainty.…”

“…Genetic test results that include identification of a VUS routinely, and understandably, incite uncertainty among patients who receive this result. Patients report feelings of worry and anxiety (Makhnoon, Garrett, Burke, Bowen, & Shirts, ; Makhnoon, Shirts, Bowen, & Fullerton, ; Solomon et al, ) and higher levels of distress about cancer risk (Richter et al, ; Vos et al, ) upon receiving a VUS result. These variants are also often misinterpreted by patients as diagnostic for disease or genetic predisposition (Vos et al, ), which leads patients and providers to engage in inappropriate clinical measures (e.g., prophylactic surgery) (Murray, Cerrato, Bennett, & Jarvik, ).…”