Uncertain Genetic Test Results for Lynch Syndrome
Condition: HNPCC
MeSH terms: Colorectal Neoplasms, Hereditary Nonpolyposis
Study type: Observational

Summary: 
      Background:

        -  Individuals have varying tolerances for receiving ambiguous information. However, not
           much is known about how ambiguous genetic testing information is received. Also, not
           much is known about how at-risk individuals internalize and process these results. More
           information is needed about how this information affects a person s life.

        -  Lynch Syndrome is a genetic condition that carries a high risk of colon cancer and other
           cancers. Individuals at risk for Lynch Syndrome can have genetic testing for it. The
           test may confirm a diagnosis and determine actions that can be taken. Results from
           genetic testing can also affect the perspectives of relatives who might also be
           affected. However, genetic testing can also produce variants of unknown significance
           (VUS). VUS are data that may not provide enough information to make decisions.
           Researchers want to study people who have received a VUS result for genetic testing for
           Lynch Syndrome.

      Objectives:

      - To learn more about the impact and experience of receiving a VUS for Lynch Syndrome genetic
      testing.

      Eligibility:

      - Individuals at least 18 years of age who have recently had a VUS result on a genetic test
      for Lynch Syndrome.

      Design:

        -  Participants will be asked to answer demographic questions. They will also have a 45- to
           60-minute phone interview.

        -  During the phone interview, participants will be asked a series of questions about their
           diagnosis. They will be asked about how they received the result and how they felt right
           after receiving it. They will also discuss who they have spoken to about the result.
    

Detailed description: 
      In the field of cancer genetics, clinicians and patients have encountered challenges related
      to the significance of unclassified genetic variants (UV) or variants of unknown significance
      (VUS). As the field of medical genetics moves toward whole genome sequencing (WGS), these
      challenges will inevitably become more frequent. VUS represent ambiguous and uncertain data,
      for which pathogenicity has not been demonstrated or excluded in published literature,
      mutation databases or on the basis of other clinical findings. Such variants present a
      clinical interpretation challenge and also evoke new counseling dilemmas for the
      understanding and psychosocial impact of uncertain genetic test results. This exploratory
      study aims to seek insight into the psychological impact of receiving a VUS through
      semi-structured interviews with 30 to 40 individuals who have received a VUS test result for
      one of the Lynch Syndrome/Hereditary Nonpolyposis Colorectal Cancer (HNPCC) mismatch repair
      genes. The interviews will focus on the experience of receiving this result and any
      cognitive, affective or behavioral effects related to the uncertainty of the result.
      Interviews will be transcribed and subjected to thematic analysis to identify themes running
      through the interviews. Understanding the impact of receiving a VUS may identify areas for
      future intervention studies to minimize negative effects of these events. Additionally, these
      data may contribute to the formulation of guidelines surrounding the consent for and
      disclosure of VUS s for other diseases and ultimately for WGS.
    

Time perspective: Retrospective
Keywords: Uncertainty; HNPCC; Lynch Syndrome; Genetic Tests