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Published on: June 8, 2020
Integrated Genetic Risk Stratification Identifies High Adenoma Detection Rates at Colonoscopy in a Real-World US
Mitchelle V Zolotarevsky1,2, Keon Karimabady1,2, Raza Muhammad1,2
1Department of Medicine, Endeavor Health, Evanston, Illinois.
Background And Aims:
Colonoscopy prevents colorectal cancer through detection and removal of precursor adenomas but remains a resource-intensive for population screening. Inherited genetic risk may improve yield of adenoma detection and prioritization of colonoscopy in higher risk individuals supporting a shift toward genetically informed screening paradigm.
Methods:
We conducted a retrospective chart review of 800 adults from a US health-system biobank who underwent colonoscopy between 2010 and 2025, with investigators blinded to genetic risk status. Participants were randomly sampled across 4 predefined genetic risk categories (Low, Intermediate, High, Very High; 200 in each group) using an externally developed and validated genetic probability model (genomic probability of colorectal cancer risk) incorporating polygenic risk scores, family history, and Lynch syndrome pathogenic variants. After applying exclusion criteria, 608 patients were included into the study. The primary outcome was adenoma detection rate (ADR). Multivariable logistic regression adjusted for age, sex, body mass index, genetic ancestry, colonoscopy indication, and year of colonoscopy. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC).
Results:
Overall ADR was 43.59% and increased from 26.27% (Low), 41.38% (Intermediate), and 54.08% (High) to 68.35% (Very High), P trend<0.001. Compared with Low-risk, adjusted odds ratios (95% confidence interval) were 1.77 (1.04-3.01), 2.40 (1.48-3.90), and 4.18 (2.21-7.91) for Intermediate-, High-, and Very High-risk groups, respectively. The absolute difference in ADR between the Very High- and Low-risk groups was 42.08 percentage points. Findings were consistent in screening-only and other sensitivity analyses. Genomic probability of colorectal cancer risk improved discrimination beyond baseline predictors (AUC 0.739 vs 0.715; ΔAUC = 0.024; P = .03).
Conclusion:
Integrated genetic risk stratification was strongly associated with adenoma detection and substantially enriched colonoscopy yield. These findings support incorporating genetic risk to prioritize colonoscopy resources more efficiently.