Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort

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Su, Yu-RuBiostatistics Unit, Kaiser Permanente Washington Health Research Institute, WA, Seattle, United States; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)

Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort

Article/chapterEnglish2023

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American association for cancer research,2023
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LIBRIS-ID:oai:DiVA.org:umu-205931
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-205931URI
https://doi.org/10.1158/1055-9965.EPI-22-0817DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:152807912URI

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Language:English
Summary in:English

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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.

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Sakoda, Lori C.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States; Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, CA, Pasadena, United States (author)
Jeon, JihyounDepartment of Epidemiology, University of Michigan, MI, Ann Arbor, United States (author)
Thomas, MintaPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Lin, YiPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Schneider, Jennifer L.Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States (author)
Udaltsova, NataliaDivision of Research, Kaiser Permanente Northern California, CA, Oakland, United States (author)
Lee, Jeffrey K.Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States; Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, CA, San Francisco, United States (author)
Lansdorp-Vogelaar, IrisDepartment of Public Health, Erasmus MC, University Medical Center, Rotterdam, Netherlands (author)
Peterse, Elisabeth F PDepartment of Public Health, Erasmus MC, University Medical Center, Rotterdam, Netherlands (author)
Zauber, Ann G.Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, United States (author)
Zheng, JiayinPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Zheng, YingyePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Hauser, ElizabethVA Cooperative Studies Program Epidemiology Center, Durham Veterans Affairs Health Care System, NC, Durham, United States (author)
Baron, John A.Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States (author)
Barry, Elizabeth L.Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (author)
Bishop, D TimothyLeeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom (author)
Brenner, HermannDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany (author)
Buchanan, Daniel D.Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, VIC, Parkville, Australia (author)
Burnett-Hartman, AndreaInstitute for Health Research, Kaiser Permanente Colorado, CO, Denver, United States (author)
Campbell, Peter T.Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia (author)
Casey, GrahamCenter for Public Health Genomics, University of Virginia, VA, Charlottesville, United States (author)
Castellví-Bel, SergiGastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain (author)
Chan, Andrew T.Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States (author)
Chang-Claude, JennyDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany (author)
Figueiredo, Jane C.Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States (author)
Gallinger, Steven J.Lunenfeld Tanenbaum Research Institute, University of Toronto, Mount Sinai Hospital, ON, Toronto, Canada (author)
Giles, Graham G.Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia (author)
Gruber, Stephen B.Department of Preventive Medicine, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States; USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (author)
Gsur, AndreaInstitute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria (author)
Gunter, Marc J.Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France (author)
Hampe, JochenDepartment of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany (author)
Hampel, HeatherDivision of Human Genetics, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, OH, Columbus, United States (author)
Harrison, Tabitha A.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Hoffmeister, MichaelDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany (author)
Hua, XinweiPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Huyghe, Jeroen R.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Jenkins, Mark A.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Melbourne, Australia (author)
Keku, Temitope O.Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, United States (author)
Marchand, Loic LeUniversity of Hawaii Cancer Center, HI, Honolulu, United States (author)
Li, LiDepartment of Family Medicine, University of Virginia, VA, Charlottesville, United States (author)
Lindblom, AnnikaKarolinska Institutet (author)
Moreno, VictorOncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (author)
Newcomb, Polly A.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Pharoah, Paul D PDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (author)
Platz, Elizabeth A.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, Liberia (author)
Potter, John D.Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Qu, ConghuiPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Rennert, GadDepartment of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center and Technion-Israel Institute of Technology, Haifa, Israel (author)
Schoen, Robert E.Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States (author)
Slattery, Martha L.Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States (author)
Song, MingyangClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States (author)
van Duijnhoven, Fränzel J BDivision of Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands (author)
van Guelpen, BethanyUmeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Onkologi(Swepub:umu)beyvan99 (author)
Vodicka, PavelDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Biomedical Center, Faculty of Medicine Pilsen, Charles University, Prague, Czech Republic (author)
Wolk, AlicjaKarolinska Institutet (author)
Woods, Michael O.Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada (author)
Wu, Anna H.Department of Preventive Medicine, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (author)
Hayes, Richard B.Division of Epidemiology, Department of Population Health, New York University School of Medicine, NY, United States (author)
Peters, UlrikePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Corley, Douglas A.Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States (author)
Hsu, LiPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Biostatistics Unit, Kaiser Permanente Washington Health Research Institute, WA, Seattle, United States; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United StatesPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States; Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, CA, Pasadena, United States (creator_code:org_t)

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In:Cancer Epidemiology, Biomarkers and Prevention: American association for cancer research32:3, s. 353-3621055-99651538-7755

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By the author/editor: Su, Yu-Ru; Sakoda, Lori C.; Jeon, Jihyoun; Thomas, Minta; Lin, Yi; Schneider, Jenni ...; show more...; Udaltsova, Natal ...; Lee, Jeffrey K.; Lansdorp-Vogelaa ...; Peterse, Elisabe ...; Zauber, Ann G.; Zheng, Jiayin; Zheng, Yingye; Hauser, Elizabet ...; Baron, John A.; Barry, Elizabeth ...; Bishop, D Timoth ...; Brenner, Hermann; Buchanan, Daniel ...; Burnett-Hartman, ...; Campbell, Peter ...; Casey, Graham; Castellví-Bel, S ...; Chan, Andrew T.; Chang-Claude, Je ...; Figueiredo, Jane ...; Gallinger, Steve ...; Giles, Graham G.; Gruber, Stephen ...; Gsur, Andrea; Gunter, Marc J.; Hampe, Jochen; Hampel, Heather; Harrison, Tabith ...; Hoffmeister, Mic ...; Hua, Xinwei; Huyghe, Jeroen R ...; Jenkins, Mark A.; Keku, Temitope O ...; Marchand, Loic L ...; Li, Li; Lindblom, Annika; Moreno, Victor; Newcomb, Polly A ...; Pharoah, Paul D ...; Platz, Elizabeth ...; Potter, John D.; Qu, Conghui; Rennert, Gad; Schoen, Robert E ...; Slattery, Martha ...; Song, Mingyang; van Duijnhoven, ...; van Guelpen, Bet ...; Vodicka, Pavel; Wolk, Alicja; Woods, Michael O ...; Wu, Anna H.; Hayes, Richard B ...; Peters, Ulrike; Corley, Douglas ...; Hsu, Li; show less...

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