Alessandro Mannucci, MD, CGA-IGC Communications Committee Member
In this first episode of the CGA-IGC Research Collaboration Podcast Series, Dr. Joshua Melson, a gastroenterologist at the University of Arizona Cancer Center, sits down with leading experts from the LINEAGE Consortium—a cutting-edge research collaboration tackling the complexities of Lynch Syndrome. This hereditary GI cancer syndrome affects 1 in 279 individuals yet remains vastly underdiagnosed due to its diverse presentation and variable penetrance. The LINEAGE Consortium is on a mission to change that.
The Need for LINEAGE: Why Now?
Dr. Swati G. Patel, a gastroenterologist from the University of Colorado, highlights the pressing need for a new approach to understanding Lynch Syndrome. Traditional data on cancer risk and management strategies have been based on high-risk families, but with advances in genetic testing—including population-based and direct-to-consumer approaches—we now recognize that Lynch Syndrome presents in a far more diverse way than previously understood.
To bridge this gap, the LINEAGE Consortium is pioneering efforts to:
Refine cancer risk assessments by studying contemporary patient populations.
Examine genetic and lifestyle risk factors to improve surveillance strategies.
Develop a digital biobank, linking genetic samples with clinical outcomes for future discoveries.
Dr. Patel emphasizes that Lynch Syndrome is often missed in clinical settings due to lack of family history documentation and variable cancer risks across patients. Contemporary practice, however, is shifting towards broader genetic testing approaches that are uncovering new Lynch cases that don’t fit the classical profile. By collecting detailed risk factor data and studying risk modification strategies, the consortium aims to redefine how we manage Lynch Syndrome patients.
What Sets LINEAGE Apart?
While previous initiatives like the Prospective Lynch Syndrome Database (PLSD) and the Colon Cancer Family Registry have been instrumental, LINEAGE brings something new to the table:
Prospective Data Collection: Moving beyond just cancer outcomes to incorporate detailed risk factor analyses.
North American Focus: Reflecting current medical practices across the continent.
Patient-Reported Outcomes: Understanding lifestyle, diet, and medication adherence—factors often missing from electronic health records.
Digital Biobank Initiative: Cataloging available biospecimens to enhance research capabilities.
Infrastructure for Future Clinical Trials: Creating a research network that can rapidly identify cohorts for cutting-edge mechanistic and interventional trials.
Dr. Patel explains that integrating patient surveys will provide critical insights into behavioral and environmental factors that impact cancer risk—something not typically captured in standard clinical data. This approach allows for a more holistic understanding of Lynch Syndrome and its various risk modifiers.
Building the Consortium: From Concept to Reality
Dr. Zachariah H. Foda (Johns Hopkins) reflects on the early planning stages of LINEAGE, emphasizing the importance of defining clear goals from the start. “If you can’t come up with a clear objective, it’s not time to start,” he notes. Establishing a strong foundation through shared values and governance structures has been essential to ensuring long-term sustainability.
Dr. Loomans-Kropp (Ohio State University) further elaborates on why a formal consortium model was necessary, rather than a looser collaborative network. The large-scale, prospective nature of LINEAGE’s objectives required a framework that could support sustained data collection and analysis over time.
A key aspect of LINEAGE’s success has been its structured charter, which outlines:
Research priorities
Membership criteria
Collaborative expectations
Data-sharing agreements
Dr. Patel notes that this document serves as a “North Star” for new institutions looking to join, ensuring alignment in goals and methodologies.
Challenges and the Road Ahead
Building a consortium of this scale isn’t easy. Some of the key hurdles faced include:
Sustaining enthusiasm and engagement across multiple institutions.
Ensuring high-quality data collection through rigorous standardization.
Navigating patient data sharing agreements in today’s regulatory landscape.
Securing long-term funding to support the infrastructure and investigators driving the research forward.
Dr. Patel stresses that data quality is paramount. LINEAGE has implemented multiple validation steps, including cross-site audits, standardized data entry protocols, and oversight from experienced geneticists and oncologists. Each site is responsible for maintaining high data accuracy, with regular reviews and compliance checks.
Dr. Patel also highlights the complexity of sharing patient data in today’s research environment. She explains how LINEAGE carefully balances patient privacy concerns with the need for data accessibility, engaging legal experts early in the process to ensure compliance with all regulations.
Looking Forward: What’s Next for LINEAGE?
Dr. Melson asks what we can expect from LINEAGE in the coming months and years. Dr. Foda and Dr. Loomans-Kropp outline several exciting upcoming developments:
Expansion of data collection efforts to include more institutions across North America.
Increased focus on patient-reported outcomes, shedding light on lifestyle and behavioral risk factors.
Development of a centralized data commons, allowing researchers easier access to pooled datasets for large-scale analysis.
Exploration of new chemo-prevention strategies, dietary interventions, and even Lynch-specific vaccines for cancer risk reduction.
Strengthening partnerships with national and international research groups to enhance collaborative potential.
Why You Should Tune In
This episode is a must-listen for clinicians, researchers, and anyone passionate about hereditary cancer syndromes. If you’re curious about the future of precision medicine, genetic epidemiology, and patient-centered research, LINEAGE is a game-changer—and this podcast is just the beginning.
🎧 Listen to the full episode now and stay tuned for upcoming discussions in this exciting research series!
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If you enjoyed this podcast, you may like others from the CGA-IGC Podcast Series (Seasons 3, 4, 5, 6 & 7) presented by the CGA-IGC Education Committee. Or, explore our Expert Approach to Hereditary Gastrointestinal Cancers podcast series (Seasons 1 and 2).
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