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000186696 1001_ $$00000-0001-6150-960X$$aSu, Yu-Ru$$b0
000186696 245__ $$aValidation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort.
000186696 260__ $$aPhiladelphia, Pa.$$bAACR$$c2023
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000186696 520__ $$aPolygenic 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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000186696 7001_ $$00000-0002-0900-5735$$aSakoda, Lori C$$b1
000186696 7001_ $$00000-0001-7003-3412$$aJeon, Jihyoun$$b2
000186696 7001_ $$00000-0001-9337-7015$$aThomas, Minta$$b3
000186696 7001_ $$00000-0001-8644-614X$$aLin, Yi$$b4
000186696 7001_ $$00000-0002-6095-7942$$aSchneider, Jennifer L$$b5
000186696 7001_ $$00000-0002-0679-4310$$aUdaltsova, Natalia$$b6
000186696 7001_ $$00000-0001-7404-4274$$aLee, Jeffrey K$$b7
000186696 7001_ $$00000-0002-9438-2753$$aLansdorp-Vogelaar, Iris$$b8
000186696 7001_ $$00000-0002-4249-6169$$aPeterse, Elisabeth F P$$b9
000186696 7001_ $$00000-0002-1764-5994$$aZauber, Ann G$$b10
000186696 7001_ $$00000-0002-5559-6847$$aZheng, Jiayin$$b11
000186696 7001_ $$00000-0002-3078-4200$$aZheng, Yingye$$b12
000186696 7001_ $$00000-0003-0367-9189$$aHauser, Elizabeth$$b13
000186696 7001_ $$00000-0003-3461-1056$$aBaron, John A$$b14
000186696 7001_ $$00000-0001-9637-3036$$aBarry, Elizabeth L$$b15
000186696 7001_ $$00000-0002-8752-8785$$aBishop, D Timothy$$b16
000186696 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b17$$udkfz
000186696 7001_ $$00000-0003-2225-6675$$aBuchanan, Daniel D$$b18
000186696 7001_ $$00000-0003-4009-0680$$aBurnett-Hartman, Andrea$$b19
000186696 7001_ $$00000-0002-5549-2036$$aCampbell, Peter T$$b20
000186696 7001_ $$00000-0003-1584-5551$$aCasey, Graham$$b21
000186696 7001_ $$00000-0003-1217-5097$$aCastellví-Bel, Sergi$$b22
000186696 7001_ $$00000-0001-7284-6767$$aChan, Andrew T$$b23
000186696 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b24$$udkfz
000186696 7001_ $$00000-0001-8040-3341$$aFigueiredo, Jane C$$b25
000186696 7001_ $$00000-0002-6998-9414$$aGallinger, Steven J$$b26
000186696 7001_ $$00000-0003-4946-9099$$aGiles, Graham G$$b27
000186696 7001_ $$00000-0001-8656-7822$$aGruber, Stephen B$$b28
000186696 7001_ $$00000-0002-9795-1528$$aGsur, Andrea$$b29
000186696 7001_ $$00000-0001-5472-6761$$aGunter, Marc J$$b30
000186696 7001_ $$00000-0002-2421-6127$$aHampe, Jochen$$b31
000186696 7001_ $$00000-0001-7558-9794$$aHampel, Heather$$b32
000186696 7001_ $$00000-0002-4173-7530$$aHarrison, Tabitha A$$b33
000186696 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b34$$udkfz
000186696 7001_ $$00000-0003-2114-2975$$aHua, Xinwei$$b35
000186696 7001_ $$00000-0001-6027-9806$$aHuyghe, Jeroen R$$b36
000186696 7001_ $$00000-0002-8964-6160$$aJenkins, Mark A$$b37
000186696 7001_ $$00000-0003-4019-3903$$aKeku, Temitope O$$b38
000186696 7001_ $$00000-0001-5013-980X$$aLe Marchand, Loic$$b39
000186696 7001_ $$aLi, Li$$b40
000186696 7001_ $$00000-0001-7675-7569$$aLindblom, Annika$$b41
000186696 7001_ $$00000-0002-2818-5487$$aMoreno, Victor$$b42
000186696 7001_ $$00000-0001-8786-0043$$aNewcomb, Polly A$$b43
000186696 7001_ $$00000-0001-8494-732X$$aPharoah, Paul D P$$b44
000186696 7001_ $$00000-0003-3676-8954$$aPlatz, Elizabeth A$$b45
000186696 7001_ $$00000-0001-5439-1500$$aPotter, John D$$b46
000186696 7001_ $$00000-0003-1927-6245$$aQu, Conghui$$b47
000186696 7001_ $$00000-0002-8512-068X$$aRennert, Gad$$b48
000186696 7001_ $$00000-0001-7153-2766$$aSchoen, Robert E$$b49
000186696 7001_ $$00000-0002-1655-6543$$aSlattery, Martha L$$b50
000186696 7001_ $$00000-0002-1324-0316$$aSong, Mingyang$$b51
000186696 7001_ $$00000-0001-8367-2352$$avan Duijnhoven, Fränzel J B$$b52
000186696 7001_ $$00000-0002-9692-101X$$aVan Guelpen, Bethany$$b53
000186696 7001_ $$00000-0003-2376-1243$$aVodicka, Pavel$$b54
000186696 7001_ $$00000-0001-7387-6845$$aWolk, Alicja$$b55
000186696 7001_ $$00000-0001-8180-418X$$aWoods, Michael O$$b56
000186696 7001_ $$00000-0003-0546-902X$$aWu, Anna H$$b57
000186696 7001_ $$00000-0002-0918-661X$$aHayes, Richard B$$b58
000186696 7001_ $$00000-0001-5666-9318$$aPeters, Ulrike$$b59
000186696 7001_ $$00000-0001-6132-5165$$aCorley, Douglas A$$b60
000186696 7001_ $$00000-0001-8168-4712$$aHsu, Li$$b61
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