Information for Health Professionals, Information for Patients, Lynch Syndrome

Variants of Unknown Significance (VUS): A new trial for Lynch Syndrome patients


Uncertain Genetic Test Results for Lynch Syndrome



  • 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.


– To learn more about the impact and experience of receiving a VUS for Lynch Syndrome genetic testing.


– Individuals at least 18 years of age who have recently had a VUS result on a genetic test for Lynch Syndrome.


  • 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.
Study Type: Observational
Study Design: Time Perspective: Retrospective
Official Title: Living in Lynch Syndrome Limbo: Exploring the Meaning of Uncertain Genetic Test Results
Further study details as provided by National Institutes of Health Clinical Center (CC):
Estimated Enrollment: 40
Study Start Date: April 2012

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.


Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes

Individuals who have received a VUS for Lynch Syndrome must be over 18, have telephone access and speak English. Individuals will be excluded if they’ve received their results less than 3 months earlier or more than 6 years ago.

  Contacts and Locations

Please refer to this study by its identifier: NCT01646112

Contact: Barbara B Biesecker (301) 496-3979

United States, Maryland
National Human Genome Research Institute (NHGRI), 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Principal Investigator: Barbara B Biesecker National Human Genome Research Institute (NHGRI)

  More Information
Publications: Identifier: NCT01646112     History of Changes
Other Study ID Numbers: 999912126, 12-HG-N126
Study First Received: July 18, 2012
Last Updated: July 18, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Lynch Syndrome
Genetic Tests

Additional relevant MeSH terms:

Colorectal Neoplasms, Hereditary Nonpolyposis
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases processed this record on September 27, 2012



About kjmonahan

Service lead for Family History of Bowel Cancer Clinic

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