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@article{Su:2023:10.1158/1055-9965.EPI-22-0817,
author = {Su, Y-R and Sakoda, LC and Jeon, J and Thomas, M and Lin, Y and Schneider, JL and Udaltsova, N and Lee, JK and Lansdorp-Vogelaar, I and Peterse, EFP and Zauber, AG and Zheng, J and Zheng, Y and Hauser, E and Baron, JA and Barry, EL and Bishop, DT and Brenner, H and Buchanan, DD and Burnett-Hartman, A and Campbell, PT and Casey, G and Castellví-Bel, S and Chan, AT and Chang-Claude, J and Figueiredo, JC and Gallinger, SJ and Giles, GG and Gruber, SB and Gsur, A and Gunter, MJ and Hampe, J and Hampel, H and Harrison, TA and Hoffmeister, M and Hua, X and Huyghe, JR and Jenkins, MA and Keku, TO and Marchand, LL and Li, L and Lindblom, A and Moreno, V and Newcomb, PA and Pharoah, PDP and Platz, EA and Potter, JD and Qu, C and Rennert, G and Schoen, RE and Slattery, ML and Song, M and van, Duijnhoven FJB and Van, Guelpen B and Vodicka, P and Wolk, A and Woods, MO and Wu, AH and Hayes, RB and Peters, U and Corley, DA and Hsu, L},
doi = {10.1158/1055-9965.EPI-22-0817},
journal = {Cancer Epidemiol Biomarkers Prev},
pages = {353--362},
title = {Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort.},
url = {http://dx.doi.org/10.1158/1055-9965.EPI-22-0817},
volume = {32},
year = {2023}
}

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TY  - JOUR
AB  - 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.
AU  - Su,Y-R
AU  - Sakoda,LC
AU  - Jeon,J
AU  - Thomas,M
AU  - Lin,Y
AU  - Schneider,JL
AU  - Udaltsova,N
AU  - Lee,JK
AU  - Lansdorp-Vogelaar,I
AU  - Peterse,EFP
AU  - Zauber,AG
AU  - Zheng,J
AU  - Zheng,Y
AU  - Hauser,E
AU  - Baron,JA
AU  - Barry,EL
AU  - Bishop,DT
AU  - Brenner,H
AU  - Buchanan,DD
AU  - Burnett-Hartman,A
AU  - Campbell,PT
AU  - Casey,G
AU  - Castellví-Bel,S
AU  - Chan,AT
AU  - Chang-Claude,J
AU  - Figueiredo,JC
AU  - Gallinger,SJ
AU  - Giles,GG
AU  - Gruber,SB
AU  - Gsur,A
AU  - Gunter,MJ
AU  - Hampe,J
AU  - Hampel,H
AU  - Harrison,TA
AU  - Hoffmeister,M
AU  - Hua,X
AU  - Huyghe,JR
AU  - Jenkins,MA
AU  - Keku,TO
AU  - Marchand,LL
AU  - Li,L
AU  - Lindblom,A
AU  - Moreno,V
AU  - Newcomb,PA
AU  - Pharoah,PDP
AU  - Platz,EA
AU  - Potter,JD
AU  - Qu,C
AU  - Rennert,G
AU  - Schoen,RE
AU  - Slattery,ML
AU  - Song,M
AU  - van,Duijnhoven FJB
AU  - Van,Guelpen B
AU  - Vodicka,P
AU  - Wolk,A
AU  - Woods,MO
AU  - Wu,AH
AU  - Hayes,RB
AU  - Peters,U
AU  - Corley,DA
AU  - Hsu,L
DO  - 10.1158/1055-9965.EPI-22-0817
EP  - 362
PY  - 2023///
SP  - 353
TI  - Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort.
T2  - Cancer Epidemiol Biomarkers Prev
UR  - http://dx.doi.org/10.1158/1055-9965.EPI-22-0817
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36622766
VL  - 32
ER  -

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