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Principal Investigator: Fay Kastrinos
Organization: UNIVERSITY OF CHICAGO
Fiscal Year: 2024
Award: $701,911
Funding agency: National Cancer Institute
PROJECT SUMMARY/ABSTRACT
Lynch syndrome (LS), the most common inherited cause of colorectal cancer (CRC) affecting ~1.2 million Amer-
icans, carries 3-8x higher lifetime CRC risk than the general population. Colonoscopy starting early in adulthood
and repeated yearly or biennially is the only recommended surveillance strategy which translates into ~25-50
lifetime colonoscopies. This intensive colonoscopy surveillance is not ideal because: a) CRC risk varies widely
by LS gene and age, b) colonoscopies are invasive, costly, and not readily accessible to all patients, and c)
adherence is suboptimal. Personalized surveillance strategies in LS that integrate non-invasive tests with colon-
oscopy would address limitations and barriers in current clinical practice but have not been previously studied.
To address these gaps, this multi-center, prospective trial will examine performance of fecal immunochemical
test (FIT) in LS patients undergoing colonoscopy surveillance. In addition to measuring FIT test characteristics
(specificity, sensitivity, negative and positive predictive value), this study will examine LS patients' attitudes and
acceptability of non-invasive tests (Aim 1). The proposal will evaluate personalized surveillance strategies in LS
that integrate non-invasive tests and colonoscopy using simulation modeling (Aim 2). An important deliverable
is the 1st well-annotated, prospective LS biobank in the US for future studies of promising biomarkers and clinical
outcomes (Aim 3). This study is timely because of the unique opportunity to harmonize data with the UK “FIT for
Lynch” study that began recruitment in 2023 in order to evaluate FIT performance in a large, international LS
cohort. Taken together, the proposal is significant because it has potential to change paradigms of CRC surveil-
lance in order to improve the lives and longevity of LS patients.
Terms: <21+ years old><Address><Adherence><Adult><Adult Human><Affect><Age><American><Attitude><Biological Markers><Blood><Blood Reticuloendothelial System><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><CRC screening><Cancers><Caring><Characteristics><Clinical><Clinical Research><Clinical Study><Collaborations><Colon Cancer><Colon Carcinoma><Colonic Adenoma><Colonic Adenomatous Polyp><Colonoscopy><Colorectal Cancer><Colorectal Neoplasms><Colorectal Tumors><Complement><Complement Proteins><Defect><Development><Emergency response><Enrollment><Evaluation><Familial Nonpolyposis Colon Cancer><Feces><Funding><Future><General Population><General Public><Genes><Geography><HNPCC><Hereditary><Hereditary Colo-rectal Endometrial Cancer Syndrome><Hereditary Colorectal Endometrial Cancer Syndrome><Hereditary Defective Mismatch Repair Syndrome><Hereditary Non-Polyposis Colon Cancer><Hereditary Nonpolyposis Colo-rectal Cancer><Hereditary Nonpolyposis Colo-rectal Neoplasms><Hereditary Nonpolyposis Colon Cancer><Hereditary Nonpolyposis Colorectal Cancer><Hereditary Nonpolyposis Colorectal Neoplasms><Incidence><Individual><Inherited><International><Knowledge><LS/HNPCC><Large Bowel Tumor><Large Intestine Neoplasm><Large Intestine Tumor><Length of Life><Longevity><Lynch Syndrome><Malignant Neoplasms><Malignant Tumor><Measures><Mismatch Repair><Modeling><Multi-center trial><Multicenter Trials><Outcome><Patients><Performance><Population Heterogeneity><Position><Positioning Attribute><Post-Replication Mismatch Repair><Predictive Value><Procedures><Prospective Studies><Prospective cohort><Recommendation><Reporting><Research><Research Resources><Resources><Risk><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Screening for cancer><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Specificity><Survey Instrument><Surveys><Testing><Translating><Translational Research><Translational Science><Triage><United Kingdom><adulthood><ages><bio-markers><biobank><biologic marker><biomarker><biorepository><blood-based biomarker><blood-based marker><cancer in the colon><clinical care><clinical practice><cohort><colon adenoma><colon adenomatous polyp><colorectal cancer detection><colorectal cancer early detection><colorectal cancer risk><colorectal cancer screening><colorectal neoplasia><complementation><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><cost><cost effective><data harmonization><detect colorectal cancer><developmental><diverse populations><early cancer detection><enroll><harmonized data><hereditary non-polyposis colo-rectal cancer><hereditary non-polyposis colorectal cancer><heterogeneous population><improved><large bowel neoplasm><life-time risk><lifetime risk><malignancy><marginalized group><marginalized individual><marginalized people><marginalized population><model-based simulation><models and simulation><neoplasm/cancer><pandemic><pandemic disease><performance tests><population diversity><prospective><recruit><screening cancer patients><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><stool><surveillance strategy><translation research><translational investigation>