Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort.
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Su Yu-Ru, Sakoda Lori C, Jeon Jihyoun, Thomas Minta, Lin Yi, Schneider Jennifer L, Udaltsova Natalia, Lee Jeffrey K, Lansdorp-Vogelaar Iris, Peterse Elisabeth F P, Zauber Ann G, Zheng Jiayin, Zheng Yingye, Hauser Elizabeth, Baron John A, Barry Elizabeth L, Bishop D Timothy, Brenner Hermann, Buchanan Daniel D, Burnett-Hartman Andrea, Campbell Peter T, Casey Graham, Castellví-Bel Sergi, Chan Andrew T, Chang-Claude Jenny, Figueiredo Jane C, Gallinger Steven J, Giles Graham G, Gruber Stephen B, Gsur Andrea, Gunter Marc J, Hampe Jochen, Hampel Heather, Harrison Tabitha A, Hoffmeister Michael, Hua Xinwei, Huyghe Jeroen R, Jenkins Mark A, Keku Temitope O, Marchand Loic Le, Li Li, Lindblom Annika, Moreno Victor, Newcomb Polly A, Pharoah Paul D P, Platz Elizabeth A, Potter John D, Qu Conghui, Rennert Gad, Schoen Robert E, Slattery Martha L, Song Mingyang, van Duijnhoven Fränzel J B, Van Guelpen Bethany, Vodicka Pavel, Wolk Alicja, Woods Michael O, Wu Anna H, Hayes Richard B, Peters Ulrike, Corley Douglas A, Hsu Li
Аннотация
METHODS: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group).
RESULTS: In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01; 95% confidence interval (CI), 0.91-1.13] and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity.
CONCLUSIONS: The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.
IMPACT: The proposed model has potential utility in risk-stratified colorectal cancer prevention.