ArticleAmerican journal of human genetics2020
Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
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In one paragraph
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 5 pooled it
19.8field-weighted citation impact, top 1% of its field
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
127 citing papers in PubMed, 5 syntheses or guidelines pooled it, 221 citations in OpenAlex.
- Colorectal Cancer Risk Loci: Prognostic Factors for Clinical Outcomes? A Systematic Review and Meta-Analysis.Cancer reports (Hoboken, N.J.) · 2025Pooled it
- Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023Guideline
- An empirical Bayes approach to improving population-specific genetic association estimation by leveraging cross-population data.Genetic epidemiology · 2023Pooled it
- Risk assessment for colorectal cancer via polygenic risk score and lifestyle exposure: a large-scale association study of East Asian and European populations.Genome medicine · 2023Pooled it
- Developing and validating polygenic risk scores for colorectal cancer risk prediction in East Asians.International journal of cancer · 2022Pooled it
- Combining genome-wide polygenic scores with registry data for colorectal cancer risk-based screening.British journal of cancer · 2026Article
- Validation of a Colorectal Cancer Risk Prediction Model in US Black Women.Cancer prevention research (Philadelphia, Pa.) · 2026Article
- Emerging trends in the global burden of colorectal cancer.Nature reviews. Clinical oncology · 2026Review
- Polygenic risk scores in cancer.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Genetic determinants of childhood onset systemic lupus erythematosus.Lupus science & medicine · 2026Article
- Machine learning-based genome-wide association analysis to construct a clinical decision model for severe neonatal jaundice.Translational pediatrics · 2026Article
- Effect of a polygenic risk score in patients with late-onset, early-onset, familial, or hereditary colorectal cancer.JNCI cancer spectrum · 2026Article
- Risk Factors in Sporadic Early-Onset Colorectal Cancer, Current Evidence and Emerging Insights: A Systematic Review.Cancers · 2026Review
- Accelerating discovery of cancer causes for prevention in the era of rising early-onset cancers.Cell · 2026Review
- MyGeneRisk Colon: A Web-Based Tool for Personalized Colorectal Cancer Risk Prediction Based on Genetics and Lifestyle.medRxiv : the preprint server for health sciences · 2026Article
- GP perspectives on genomics in primary care: a qualitative study on using polygenic risk scores to evaluate cancer risk.The British journal of general practice : the journal of the Royal College of General Practitioners · 2026Article
- Optimizing colorectal cancer screening through polygenic risk score-based risk stratification: evidence from a population-based cohort and screening trial.Genome medicine · 2026Article
- Polygenic Risk for Pre-Eclampsia and the Long-Term Risk of Incident Hypertension and Cardiovascular Disease: A Population-Based Cohort Study.BJOG : an international journal of obstetrics and gynaecology · 2026Article
- Validation and context-dependent effects of a prostate cancer polygenic risk score in the All of Us Research Program.American journal of human genetics · 2026Article
- Performance of different polygenic risk scores for breast cancer risk prediction: in-depth evaluations across large UK and Australian cohorts.European journal of human genetics : EJHG · 2026Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
97 authors at 20 institutions in 11 countries.
Minta ThomasPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Lori C SakodaPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.
Michael HoffmeisterDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Elisabeth A RosenthalDepartment of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA 98195, USA.
Jeffrey K LeeDivision of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.
Franzel J B van DuijnhovenDivision of Human Nutrition and Health, Wageningen University & Research, Wageningen 176700, the Netherlands.
Elizabeth A PlatzDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Anna H WuUniversity of Southern California, Preventative Medicine, Los Angeles, CA 90089, USA.
Christopher H DampierDepartment of Surgery, University of Virginia Health System, Charlottesville, VA 22903, USA.
Albert de la ChapelleDepartment of Cancer Biology and Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Alicja WolkInstitute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden.
Amit D JoshiClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Andrea Burnett-HartmanInstitute for Health Research, Kaiser Permanente Colorado, Denver, CO 80014, USA.
Andrea GsurInstitute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna 1090, Austria.
Annika LindblomDepartment of Clinical Genetics, Karolinska University Hospital, Stockholm 17177, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 17177, Sweden.
Antoni CastellsGastroenterology 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 08007, Spain.
Aung Ko WinCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3000, Australia.
Bahram NamjouCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Cincinnati VA Medical Center, Cincinnati, OH 45229, USA.
Bethany Van GuelpenDepartment of Radiation Sciences, Oncology Unit, Umeå University, Umeå 90187, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå 90187, Sweden.
Catherine M TangenSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Qianchuan HePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Christopher I LiPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Clemens SchafmayerDepartment of General Surgery, University Hospital Rostock, Rostock 18051, Germany.
Corinne E JoshuDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Cornelia M UlrichHuntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA.
D Timothy BishopLeeds Institute of Cancer and Pathology, University of Leeds, Leeds LS2 9JT, UK.
Daniel D BuchananUniversity of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC 3010, Australia; Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, VIC 3010, Australia.
Daniel SchaidDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
David A DrewClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
David C MullerSchool of Public Health, Imperial College London, London SW7 2AZ, UK.
David DugganTranslational Genomics Research Institute - An Affiliate of City of Hope, Phoenix, AZ 85003, USA.
David R CrosslinDepartment of Bioinformatics and Medical Education, University of Washington Medical Center, Seattle, WA 98195, USA.
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Edward L GiovannucciDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02108, USA.
Eric LarsonKaiser Permanente Washington Research Institute, Seattle, WA 98101, USA.
Flora QuPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Frank MentchCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Graham G GilesCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3000, Australia; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC 3004, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia.
Hakon HakonarsonCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Heather HampelDivision of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Ian B StanawayDepartment of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA 98195, USA.
Jane C FigueiredoDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Jeroen R HuyghePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Jessica MinnierSchool of Public Health, Oregon Health & Science University, Portland, OR 97239, USA.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, 69120 Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg 20246, Germany.
Jochen HampeDepartment of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden 01062, Germany.
John B HarleyCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Cincinnati VA Medical Center, Cincinnati, OH 45229, USA.
Kala VisvanathanDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Keith R CurtisPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Kenneth OffitClinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Department of Medicine, Weill Cornell Medical College, NY 10065, USA.
Li LiDepartment of Family Medicine, University of Virginia, Charlottesville, VA 22903, USA.
Loic Le MarchandUniversity of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Ludmila VodickovaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague 4, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 128 00 Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, 323 00 Pilsen, Czech Republic.
Marc J GunterNutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon 69372, France.
Mark A JenkinsCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3000, Australia.
Martha L SlatteryDepartment of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA.
Mathieu LemirePanCuRx Translational Research Initiative, Ontario, Institute for Cancer Research, Toronto, ON M5G0A3, Canada.
Michael O WoodsMemorial University of Newfoundland, Discipline of Genetics, St. John's, NL A1B 3R7, Canada.
Mingyang SongClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
Neil MurphyNutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon 69372, France.
Noralane M LindorDepartment of Health Science Research, Mayo Clinic, Scottsdale, AZ 85260, USA.
Ozan DikilitasDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Paul D P PharoahDepartment of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK.
Peter T CampbellBehavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA 30303, USA.
Polly A NewcombPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; School of Public Health, University of Washington, Seattle, WA 98195, USA.
Roger L MilneCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3000, Australia; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC 3004, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia.
Robert J MacInnisCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3000, Australia; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC 3004, Australia.
Sergi Castellví-BelGastroenterology 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 08007, Spain.
Shuji OginoDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Stéphane BézieauService de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes 44093, France.
Stephen N ThibodeauDivision of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 85054, USA.
Steven J GallingerLunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON M5G1X5, Canada.
Syed H ZaidiOntario Institute for Cancer Research, Toronto, ON M5G0A3, Canada.
Tabitha A HarrisonPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Temitope O KekuCenter for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC 27599, USA.
Thomas J HudsonOntario Institute for Cancer Research, Toronto, ON M5G0A3, Canada.
Veronika VymetalkovaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague 4, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 128 00 Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, 323 00 Pilsen, Czech Republic.
Victor MorenoOncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona 08908, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid 28029, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona 08907, Spain; ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08908, Spain.
Vicente MartínCIBER Epidemiología y Salud Pública (CIBERESP), Madrid 28029, Spain; Biomedicine Institute (IBIOMED), University of León, León 24071, Spain.
Volker ArndtDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Wei-Qi WeiDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Wendy ChungOffice of Research & Development, Department of Veterans Affairs, Washington, DC 20420, USA; Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Yu-Ru SuPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Richard B HayesDivision of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY 10016, USA.
Emily WhitePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.
Pavel VodickaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague 4, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 128 00 Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, 323 00 Pilsen, Czech Republic.
Graham CaseyCenter for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA.
Stephen B GruberDepartment of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Robert E SchoenDepartment of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA.
Andrew T ChanClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
John D PotterPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Centre for Public Health Research, Massey University, Wellington 6140, New Zealand.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg 69120, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Gail P JarvikDepartment of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA 98195, USA; Genome Sciences, University of Washington Medical Center, Seattle, WA 98195, USA.
Douglas A CorleyDivision of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA. Electronic address: upeters@fredhutch.org.
Li HsuPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA. Electronic address: lih@fredhutch.org.
Fred Hutch Cancer Center · USKaiser Permanente · USUniversity of Melbourne · AUUniversity of Washington Medical Center · USHarvard University · USOntario Institute for Cancer Research · CACentre International de Recherche sur le Cancer · FRChildren's Hospital of Philadelphia · USCzech Academy of Sciences · CZGerman Cancer Research Center · DEHeidelberg University · DEJohns Hopkins University · USMayo Clinic in Florida · USNational Institutes of Health · USThe Ohio State University · USUniversity of Southern California · USUniversity of Utah · USUniversity of Virginia · USUniversity of Washington · USAmerican Cancer Society · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MSWOG Foreign AccrualsU10CA037429 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BLANKE, CHARLES D., MEYSKENS, FRANK L. · 1985 to 2014
$205.2MSWOG NCORP Research BaseUG1CA189974 · NCI · THE HOPE FOUNDATION · PI CHARLES D. BLANKE, DAWN HERSHMAN · 2014 to 2026
$80.6MPLCO Trial Etiologic and Early Marker StudyZIACP010152 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI MOORE, STEVEN · 2009 to 2025
$29.9MLong Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3MMolecular pathological epidemiology of colorectal cancerU01CA137088 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2009 to 2018
$21.8MData sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8MPostdoctoral Training Grant for MDs in Surgical Oncology ResearchT32CA163177 · NCI · UNIVERSITY OF VIRGINIA · PI Craig Lee Slingluff, Allan Tsung · 2011 to 2026
$4.6MEvaluating a Risk Prediction Model for Lung CancerK07CA188142 · NCI · KAISER FOUNDATION RESEARCH INSTITUTE · PI SAKODA, LORI · 2015 to 2019
$920kCancer Research UK 10589Cancer Research UK 19167Cancer Research UK 24390NCI NIH HHS P30 CA008748World Health Organization 001
Abstract
Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
Indexed as
Genetic Predisposition to DiseaseRisk AssessmentAgedAsian PeopleBayes TheoremColorectal NeoplasmsFemaleGenome, HumanGenome-Wide Association StudyHumansMaleMiddle AgedMultifactorial InheritancePolymorphism, Single NucleotideRisk Factorscancer risk predictioncolorectal cancermachine learningpolygenic risk score
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