Lynch Syndrome Integrative Epidemiology and Genetics (LINEAGE)

Lynch Syndrome Integrative Epidemiology and Genetics (LINEAGE)

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

Study Overview

• Status: Recruiting
• Conditions: Lynch Syndrome

Detailed Description

The main objective of this consortium is to build a shared resource to drive research in critical areas necessary to understand LS-related neoplasia risk and improve early detection and prevention of LS-associated cancers. This consortium will provide intellectual and infrastructure support to facilitate development of research questions, collection of standardized clinical data and biospecimens, support grant applications, and generate collaborative manuscripts.

Data and samples collected for LINEAGE will allow the consortium to address a variety of topic areas including but not limited to:

I. Risk of prevalent and incident colorectal neoplasia among PV/LPV carriers. II. Estimate risk of prevalent and incident extra-colonic neoplasm among PV/LPV carriers.

III. Characterization of post-colonoscopy colorectal cancer among PV/LPV carriers.

IV. Risk factors for prevalent and incident neoplasia.

The LINEAGE Consortium is an observational prospective cohort study, with baseline and annual electronic health record (EHR) abstraction, and electronic participant and provider surveys. The consortium may also collect single or serial biosamples from identified and enrolled LS patients at participating centers.

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

• Study Contact: Name: Swati G Patel, MD, MS; Phone Number: 3032170731; Email: swati.patel@cuanschutz.edu
• Study Contact Backup: Name: Sonia Kupfer, MD

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Contact: Sandra Boimbo, MPH; Phone Number: 303-724-8892; Email: Sandra.Boimbo@cuanschutz.edu
      • Contact: Swati G Patel, MD, MS
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Not yet recruiting
      • University of Chicago
      • Contact: Sonia Kupfer, MD
      • Contact: Ophir Gilad; Phone Number: 774-702-1000; Email: ophirg@bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria:

• • 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.

Exclusion Criteria:

• Age under 18

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colorectal cancer incidence	cases of adenocarcinoma of the colon or rectum diagnosed over the observation period	40 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
non-colorectal cancer incidence	new cases of any cancer diagnosed over observation period	40 years
precancerous colorectal polyps	new diagnoses of any of the following polyps in the colon or rectum; tubular adenoma; villous adenoma; tubulovillous adenoma; sessile serrated lesion; traditional serrated adenoma	40 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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. Erratum In: Genet Med. 2020 Sep;22(9):1569. doi: 10.1038/s41436-020-0892-4.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): December 31, 2054
• Study Completion (Estimated): December 31, 2054

Study Registration Dates

• First Submitted: August 30, 2024
• First Submitted That Met QC Criteria: August 30, 2024
• First Posted (Actual): September 3, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Genetic Diseases, Inborn; Metabolic Diseases; Intestinal Diseases; Disease; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Syndrome; Colorectal Neoplasms, Hereditary Nonpolyposis
• Other Study ID Numbers: 24-0163

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not have IRB approval to do this at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No