Lynch Syndrome Integrative Epidemiology and Genetics

NCT06582914 | Recruiting

• 1 other identifier: 24-0163
• Study Type: observational
• Target: 5,000
• Locations: 1 country
• Sites: 2

Brief Summary

The vision of the "Lynch syndrome INtegrative Epidemiology And GEnetics" (LINEAGE) Consortium is to collaboratively improve the lives and longevity of individuals and families with Lynch syndrome. The mission of the LINEAGE Consortium is to collaboratively improve Lynch syndrome care through high-quality research. This consortium will provide intellectual and infrastructure support to facilitate development of research questions, collection of standardized data and biospecimens, support of grant applications, and generation of collaborative manuscripts. Our aims are to: I. Establish a prospective cohort of individuals with Lynch syndrome II. Collect standardized longitudinal clinical and biosample data to elucidate Lynch Syndrome epidemiology and gene-host interactions III. Promote intervention trials to improve cancer prevention and early detection in Lynch Syndrome

Conditions

Lynch Syndrome

Outcome Measures

Primary Outcomes (1)

• Colorectal cancer incidence

  cases of adenocarcinoma of the colon or rectum diagnosed over the observation period

  40 years

Secondary Outcomes (2)

• non-colorectal cancer incidence

  40 years

• precancerous colorectal polyps

  40 years

Study Arms (1)

Pateints with a germline variant in a mismatch repair gene

Individuals with germline genetic testing results showing a pathogenic, likely pathogenic or variant of uncertain significance in MLH1, MSH2, MSH6, PMS2 or EPCAM.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with Lynch Syndrome, defined as having a pathogenic or likely pathogenic variant in a mismatch repair gene (MLH1, MSH2, MSH6, PMS2, EPCAM) on germline genetic testing.

You may qualify if:

• Adults age over 18 years
• Eligible patients must have at least one variant of uncertain significance (VUS), pathogenic or likely pathogenic variant (PV/LPV) in MLH1, MSH2, MSH6, PMS2, or EPCAM, which will be confirmed by genetic testing results (obtained as part of routine care) and a review of the variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/).
• Individuals who are an obligate carrier of a LS PV/LPV that is confirmed in the family.

You may not qualify if:

• Age under 18

Sponsors & Collaborators

• University of Colorado, Denver: lead
• University of Chicago: collaborator
• University of Kansas: collaborator
• University of Pennsylvania: collaborator
• Johns Hopkins University: collaborator
• City of Hope National Medical Center: collaborator
• Loma Linda University: collaborator
• MedStar Health: collaborator
• University of Arizona: collaborator
• University of Manitoba: collaborator
• University of Michigan: collaborator
• University of North Carolina: collaborator
• University of Pittsburgh: collaborator
• University of Rochester: collaborator
• Dana-Farber Cancer Institute: collaborator
• University of Wisconsin, Madison: collaborator
• The Cleveland Clinic: collaborator
• University of California, San Diego: collaborator
• Kaiser Permanente: collaborator
• Ohio State University: collaborator
• Virginia Mason Hospital/Medical Center: collaborator
• University of Alabama at Birmingham: collaborator
• University of Miami: collaborator

Study Sites (2)

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

NOT YET RECRUITING

Related Publications (4)

• Yao MD, von Rosenvinge EC, Groden C, Mannon PJ. Multiple endoscopic biopsies in research subjects: safety results from a National Institutes of Health series. Gastrointest Endosc. 2009 Apr;69(4):906-10. doi: 10.1016/j.gie.2008.05.015. Epub 2009 Jan 10.

  PMID: 19136110 BACKGROUND

• Kind AJH, Buckingham WR. Making Neighborhood-Disadvantage Metrics Accessible - The Neighborhood Atlas. N Engl J Med. 2018 Jun 28;378(26):2456-2458. doi: 10.1056/NEJMp1802313. No abstract available.

  PMID: 29949490 BACKGROUND

• Dominguez-Valentin M, Sampson JR, Seppala TT, Ten Broeke SW, Plazzer JP, Nakken S, Engel C, Aretz S, Jenkins MA, Sunde L, Bernstein I, Capella G, Balaguer F, Thomas H, Evans DG, Burn J, Greenblatt M, Hovig E, de Vos Tot Nederveen Cappel WH, Sijmons RH, Bertario L, Tibiletti MG, Cavestro GM, Lindblom A, Della Valle A, Lopez-Kostner F, Gluck N, Katz LH, Heinimann K, Vaccaro CA, Buttner R, Gorgens H, Holinski-Feder E, Morak M, Holzapfel S, Huneburg R, Knebel Doeberitz MV, Loeffler M, Rahner N, Schackert HK, Steinke-Lange V, Schmiegel W, Vangala D, Pylvanainen K, Renkonen-Sinisalo L, Hopper JL, Win AK, Haile RW, Lindor NM, Gallinger S, Le Marchand L, Newcomb PA, Figueiredo JC, Thibodeau SN, Wadt K, Therkildsen C, Okkels H, Ketabi Z, Moreira L, Sanchez A, Serra-Burriel M, Pineda M, Navarro M, Blanco I, Green K, Lalloo F, Crosbie EJ, Hill J, Denton OG, Frayling IM, Rodland EA, Vasen H, Mints M, Neffa F, Esperon P, Alvarez K, Kariv R, Rosner G, Pinero TA, Gonzalez ML, Kalfayan P, Tjandra D, Winship IM, Macrae F, Moslein G, Mecklin JP, Nielsen M, Moller P. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med. 2020 Jan;22(1):15-25. doi: 10.1038/s41436-019-0596-9. Epub 2019 Jul 24.

  PMID: 31337882 BACKGROUND

• Win AK, Jenkins MA, Dowty JG, Antoniou AC, Lee A, Giles GG, Buchanan DD, Clendenning M, Rosty C, Ahnen DJ, Thibodeau SN, Casey G, Gallinger S, Le Marchand L, Haile RW, Potter JD, Zheng Y, Lindor NM, Newcomb PA, Hopper JL, MacInnis RJ. Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer. Cancer Epidemiol Biomarkers Prev. 2017 Mar;26(3):404-412. doi: 10.1158/1055-9965.EPI-16-0693. Epub 2016 Oct 31.

  PMID: 27799157 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

A standardized procedure for collection and processing of human blood, stool, fresh frozen tissue, and formalin fixed paraffin embedded tissue for the LINEAGE Consortium can be used for all biosamples collected as part of the study. Barcoded samples will be stored at the clinical centers, using the specific labels for the LINEAGE study and corresponding data will be entered into the study database. Any center-specific processing differences should also be recorded by each center.

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Swati G Patel, MD, MS

CONTACT

3032170731; swati.patel@cuanschutz.edu

Sonia Kupfer, MD

CONTACT

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 40 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2024
• First Posted: September 3, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): December 31, 2054
• Study Completion (Estimated): December 31, 2054
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)