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| Home > Publications database > Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort. > print |
| 001 | 186696 | ||
| 005 | 20240229154902.0 | ||
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| 100 | 1 | _ | |a Su, Yu-Ru |0 0000-0001-6150-960X |b 0 |
| 245 | _ | _ | |a Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort. |
| 260 | _ | _ | |a Philadelphia, Pa. |c 2023 |b AACR |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1679472413_6245 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer (CRC) screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced CRC risk model comprising 140 known CRC loci to provide a comprehensive assessment on prediction performance.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 CRC 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 45-74 years (screening-eligible age group) and 40-49 years with no endoscopy history (younger-age group).In European-ancestral individuals, the predicted 5-year risk calibrated well (E/O=1.01 (95%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-value<0.001) and 0.14 (p-value=0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER CRC-incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (p-value<0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (p-value=0.04) with similar specificity.The proposed PRS-enhanced model provides a well-calibrated 5-year CRC risk prediction and improves discriminatory accuracy in the external cohort.The proposed model has potential utility in risk-stratified CRC prevention. |
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| 700 | 1 | _ | |a Sakoda, Lori C |0 0000-0002-0900-5735 |b 1 |
| 700 | 1 | _ | |a Jeon, Jihyoun |0 0000-0001-7003-3412 |b 2 |
| 700 | 1 | _ | |a Thomas, Minta |0 0000-0001-9337-7015 |b 3 |
| 700 | 1 | _ | |a Lin, Yi |0 0000-0001-8644-614X |b 4 |
| 700 | 1 | _ | |a Schneider, Jennifer L |0 0000-0002-6095-7942 |b 5 |
| 700 | 1 | _ | |a Udaltsova, Natalia |0 0000-0002-0679-4310 |b 6 |
| 700 | 1 | _ | |a Lee, Jeffrey K |0 0000-0001-7404-4274 |b 7 |
| 700 | 1 | _ | |a Lansdorp-Vogelaar, Iris |0 0000-0002-9438-2753 |b 8 |
| 700 | 1 | _ | |a Peterse, Elisabeth F P |0 0000-0002-4249-6169 |b 9 |
| 700 | 1 | _ | |a Zauber, Ann G |0 0000-0002-1764-5994 |b 10 |
| 700 | 1 | _ | |a Zheng, Jiayin |0 0000-0002-5559-6847 |b 11 |
| 700 | 1 | _ | |a Zheng, Yingye |0 0000-0002-3078-4200 |b 12 |
| 700 | 1 | _ | |a Hauser, Elizabeth |0 0000-0003-0367-9189 |b 13 |
| 700 | 1 | _ | |a Baron, John A |0 0000-0003-3461-1056 |b 14 |
| 700 | 1 | _ | |a Barry, Elizabeth L |0 0000-0001-9637-3036 |b 15 |
| 700 | 1 | _ | |a Bishop, D Timothy |0 0000-0002-8752-8785 |b 16 |
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| 700 | 1 | _ | |a Buchanan, Daniel D |0 0000-0003-2225-6675 |b 18 |
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| 700 | 1 | _ | |a Campbell, Peter T |0 0000-0002-5549-2036 |b 20 |
| 700 | 1 | _ | |a Casey, Graham |0 0000-0003-1584-5551 |b 21 |
| 700 | 1 | _ | |a Castellví-Bel, Sergi |0 0000-0003-1217-5097 |b 22 |
| 700 | 1 | _ | |a Chan, Andrew T |0 0000-0001-7284-6767 |b 23 |
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| 700 | 1 | _ | |a Figueiredo, Jane C |0 0000-0001-8040-3341 |b 25 |
| 700 | 1 | _ | |a Gallinger, Steven J |0 0000-0002-6998-9414 |b 26 |
| 700 | 1 | _ | |a Giles, Graham G |0 0000-0003-4946-9099 |b 27 |
| 700 | 1 | _ | |a Gruber, Stephen B |0 0000-0001-8656-7822 |b 28 |
| 700 | 1 | _ | |a Gsur, Andrea |0 0000-0002-9795-1528 |b 29 |
| 700 | 1 | _ | |a Gunter, Marc J |0 0000-0001-5472-6761 |b 30 |
| 700 | 1 | _ | |a Hampe, Jochen |0 0000-0002-2421-6127 |b 31 |
| 700 | 1 | _ | |a Hampel, Heather |0 0000-0001-7558-9794 |b 32 |
| 700 | 1 | _ | |a Harrison, Tabitha A |0 0000-0002-4173-7530 |b 33 |
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| 700 | 1 | _ | |a Hua, Xinwei |0 0000-0003-2114-2975 |b 35 |
| 700 | 1 | _ | |a Huyghe, Jeroen R |0 0000-0001-6027-9806 |b 36 |
| 700 | 1 | _ | |a Jenkins, Mark A |0 0000-0002-8964-6160 |b 37 |
| 700 | 1 | _ | |a Keku, Temitope O |0 0000-0003-4019-3903 |b 38 |
| 700 | 1 | _ | |a Le Marchand, Loic |0 0000-0001-5013-980X |b 39 |
| 700 | 1 | _ | |a Li, Li |b 40 |
| 700 | 1 | _ | |a Lindblom, Annika |0 0000-0001-7675-7569 |b 41 |
| 700 | 1 | _ | |a Moreno, Victor |0 0000-0002-2818-5487 |b 42 |
| 700 | 1 | _ | |a Newcomb, Polly A |0 0000-0001-8786-0043 |b 43 |
| 700 | 1 | _ | |a Pharoah, Paul D P |0 0000-0001-8494-732X |b 44 |
| 700 | 1 | _ | |a Platz, Elizabeth A |0 0000-0003-3676-8954 |b 45 |
| 700 | 1 | _ | |a Potter, John D |0 0000-0001-5439-1500 |b 46 |
| 700 | 1 | _ | |a Qu, Conghui |0 0000-0003-1927-6245 |b 47 |
| 700 | 1 | _ | |a Rennert, Gad |0 0000-0002-8512-068X |b 48 |
| 700 | 1 | _ | |a Schoen, Robert E |0 0000-0001-7153-2766 |b 49 |
| 700 | 1 | _ | |a Slattery, Martha L |0 0000-0002-1655-6543 |b 50 |
| 700 | 1 | _ | |a Song, Mingyang |0 0000-0002-1324-0316 |b 51 |
| 700 | 1 | _ | |a van Duijnhoven, Fränzel J B |0 0000-0001-8367-2352 |b 52 |
| 700 | 1 | _ | |a Van Guelpen, Bethany |0 0000-0002-9692-101X |b 53 |
| 700 | 1 | _ | |a Vodicka, Pavel |0 0000-0003-2376-1243 |b 54 |
| 700 | 1 | _ | |a Wolk, Alicja |0 0000-0001-7387-6845 |b 55 |
| 700 | 1 | _ | |a Woods, Michael O |0 0000-0001-8180-418X |b 56 |
| 700 | 1 | _ | |a Wu, Anna H |0 0000-0003-0546-902X |b 57 |
| 700 | 1 | _ | |a Hayes, Richard B |0 0000-0002-0918-661X |b 58 |
| 700 | 1 | _ | |a Peters, Ulrike |0 0000-0001-5666-9318 |b 59 |
| 700 | 1 | _ | |a Corley, Douglas A |0 0000-0001-6132-5165 |b 60 |
| 700 | 1 | _ | |a Hsu, Li |0 0000-0001-8168-4712 |b 61 |
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