Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort

0582277 - ÚEM 2024 RIV US eng J - Článek v odborném periodiku
Su, Y.R. - Sakoda, L.C. - Jeon, J. - Thomas, M. - Lin, Y. - Schneider, J.L. - Udaltsová, N. - Lee, J.K. - Lansdorp-Vogelaar, I. - Peterse, E.F.P. - Zauber, A.G. - Zheng, J. - Zheng, Y. - Hauser, E. - Baron, J.A. - Barry, E.L. - Bishop, D.T. - Brenner, H. - Buchanan, D.D. - Burnett-Hartman, A. - Campbell, P.T. - Casey, G. - Castellví-Bel, S. - Chan, A.T. - Chang-Claude, J. - Vodička, Pavel … celkem 62 autorů
Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort.
Cancer Epidemiology Biomarkers & Prevention. Roč. 32, č. 3 (2023), s. 353-362. ISSN 1055-9965. E-ISSN 1538-7755
Institucionální podpora: RVO:68378041
Klíčová slova: epidemiology research * breast-cancer * adult health * probabilities * history * scores
Obor OECD: Human genetics
Impakt faktor: 3.8, rok: 2022
Způsob publikování: Open access
https://aacrjournals.org/cebp/article-abstract/32/3/353/718479/Validation-of-a-Genetic-Enhanced-Risk-Prediction?redirectedFrom=fulltext

Background: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.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 cal-ibration 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.
Trvalý link: https://hdl.handle.net/11104/0350981