Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort Journal Article
| Authors: | Su, Y. R.; Sakoda, L. C.; Jeon, J.; Thomas, M.; Lin, Y.; Schneider, J. L.; Udaltsova, 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.; Figueiredo, J. C.; Gallinger, S. J.; Giles, G. G.; Gruber, S. B.; Gsur, A.; Gunter, M. J.; Hampe, J.; Hampel, H.; Harrison, T. A.; Hoffmeister, M.; Hua, X.; Huyghe, J. R.; Jenkins, M. A.; Keku, T. O.; Marchand, L. L.; Li, L.; Lindblom, A.; Moreno, V.; Newcomb, P. A.; Pharoah, P. D. P.; Platz, E. A.; Potter, J. D.; Qu, C.; Rennert, G.; Schoen, R. E.; Slattery, M. L.; Song, M.; van Duijnhoven, F. J. B.; Van Guelpen, B.; Vodicka, P.; Wolk, A.; Woods, M. O.; Wu, A. H.; Hayes, R. B.; Peters, U.; Corley, D. A.; Hsu, L. |
| Article Title: | Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort |
| Abstract: | 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 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. ©2023 American Association for Cancer Research. |
| Keywords: | aged; middle aged; risk factors; risk factor; risk assessment; colorectal neoplasms; colorectal tumor; humans; human |
| Journal Title: | Cancer Epidemiology Biomarkers and Prevention |
| Volume: | 32 |
| Issue: | 3 |
| ISSN: | 1055-9965 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2023-03-01 |
| Start Page: | 353 |
| End Page: | 362 |
| Language: | English |
| DOI: | 10.1158/1055-9965.Epi-22-0817 |
| PUBMED: | 36622766 |
| PROVIDER: | scopus |
| PMCID: | PMC9992158 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
