Alexi N Archambault1, Jihyoun Jeon2, Yi Lin3, Minta Thomas3, Tabitha A Harrison3, D Timothy Bishop4, Hermann Brenner5,6,7, Graham Casey8, Andrew T Chan9,10,11,12,13,14, Jenny Chang-Claude15,16, Jane C Figueiredo17,18, Steven Gallinger19, Stephen B Gruber20, Marc J Gunter21, Feng Guo5, Michael Hoffmeister5, Mark A Jenkins22, Temitope O Keku23, Loïc Le Marchand24, Li Li25, Victor Moreno26,27,28,29, Polly A Newcomb3,30, Rish Pai31, Patrick S Parfrey32, Gad Rennert33,34,35, Lori C Sakoda3,36, Jeffrey K Lee36, Martha L Slattery37, Mingyang Song9,11,38, Aung Ko Win22, Michael O Woods39, Neil Murphy40, Peter T Campbell41, Yu-Ru Su42, Iris Lansdorp-Vogelaar43, Elisabeth F P Peterse43, Yin Cao44,45,46, Anne Zeleniuch-Jacquotte1, Peter S Liang47, Mengmeng Du48, Douglas A Corley36, Li Hsu3,49, Ulrike Peters3,50, Richard B Hayes1. 1. Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, USA. 2. Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA. 3. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 4. Leeds Institute of Medical Research, St. James's University of Leeds, Leeds, UK. 5. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. 6. Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. 7. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. 8. Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA. 9. Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA. 10. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. 11. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA. 12. Broad Institute of Harvard and MIT, Cambridge, MA, USA. 13. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. 14. Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. 15. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 16. University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany. 17. Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 18. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 19. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. 20. Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA. 21. Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France. 22. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. 23. Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. 24. Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA. 25. Department of Family Medicine, University of Virginia, Charlottesville, VA, USA. 26. Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. 27. CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. 28. Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain. 29. ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. 30. School of Public Health, University of Washington, Seattle, WA, USA. 31. Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA. 32. Faculty of Medicine, Memorial University, St John's, NL, Canada. 33. Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. 34. Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. 35. Clalit National Cancer Control Center, Haifa, Israel. 36. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. 37. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. 38. Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. 39. Discipline of Genetics, Memorial University of Newfoundland, St John's, NL, Canada. 40. Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. 41. Department of Population Science, American Cancer Society, Atlanta, GA, USA. 42. Biostatistics Unit, Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA. 43. Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands. 44. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA. 45. Washington University School of Medicine, Alvin J. Siteman Cancer Center, St Louis, MO, USA. 46. Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. 47. Department of Medicine, New York University School of Medicine, New York, NY, USA. 48. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 49. Department of Biostatistics, University of Washington, Seattle, WA, USA. 50. Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
Abstract
BACKGROUND: The incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants. METHODS: Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. RESULTS: Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores. CONCLUSIONS: Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.
BACKGROUND: The incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants. METHODS: Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. RESULTS: Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores. CONCLUSIONS: Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.
Authors: Amir Qaseem; Carolyn J Crandall; Reem A Mustafa; Lauri A Hicks; Timothy J Wilt; Mary Ann Forciea; Nick Fitterman; Carrie A Horwitch; Devan Kansagara; Michael Maroto; Robert M McLean; Jairo Roa; Janice Tufte Journal: Ann Intern Med Date: 2019-11-05 Impact factor: 25.391
Authors: Malcolm G Dunlop; Sara E Dobbins; Susan Mary Farrington; Angela M Jones; Claire Palles; Nicola Whiffin; Albert Tenesa; Sarah Spain; Peter Broderick; Li-Yin Ooi; Enric Domingo; Claire Smillie; Marc Henrion; Matthew Frampton; Lynn Martin; Graeme Grimes; Maggie Gorman; Colin Semple; Yusanne P Ma; Ella Barclay; James Prendergast; Jean-Baptiste Cazier; Bianca Olver; Steven Penegar; Steven Lubbe; Ian Chander; Luis G Carvajal-Carmona; Stephane Ballereau; Amy Lloyd; Jayaram Vijayakrishnan; Lina Zgaga; Igor Rudan; Evropi Theodoratou; John M Starr; Ian Deary; Iva Kirac; Dujo Kovacević; Lauri A Aaltonen; Laura Renkonen-Sinisalo; Jukka-Pekka Mecklin; Koichi Matsuda; Yusuke Nakamura; Yukinori Okada; Steven Gallinger; David J Duggan; David Conti; Polly Newcomb; John Hopper; Mark A Jenkins; Fredrick Schumacher; Graham Casey; Douglas Easton; Mitul Shah; Paul Pharoah; Annika Lindblom; Tao Liu; Christopher G Smith; Hannah West; Jeremy P Cheadle; Rachel Midgley; David J Kerr; Harry Campbell; Ian P Tomlinson; Richard S Houlston Journal: Nat Genet Date: 2012-05-27 Impact factor: 38.330
Authors: Ian P M Tomlinson; Luis G Carvajal-Carmona; Sara E Dobbins; Albert Tenesa; Angela M Jones; Kimberley Howarth; Claire Palles; Peter Broderick; Emma E M Jaeger; Susan Farrington; Annabelle Lewis; James G D Prendergast; Alan M Pittman; Evropi Theodoratou; Bianca Olver; Marion Walker; Steven Penegar; Ella Barclay; Nicola Whiffin; Lynn Martin; Stephane Ballereau; Amy Lloyd; Maggie Gorman; Steven Lubbe; Bryan Howie; Jonathan Marchini; Clara Ruiz-Ponte; Ceres Fernandez-Rozadilla; Antoni Castells; Angel Carracedo; Sergi Castellvi-Bel; David Duggan; David Conti; Jean-Baptiste Cazier; Harry Campbell; Oliver Sieber; Lara Lipton; Peter Gibbs; Nicholas G Martin; Grant W Montgomery; Joanne Young; Paul N Baird; Steven Gallinger; Polly Newcomb; John Hopper; Mark A Jenkins; Lauri A Aaltonen; David J Kerr; Jeremy Cheadle; Paul Pharoah; Graham Casey; Richard S Houlston; Malcolm G Dunlop Journal: PLoS Genet Date: 2011-06-02 Impact factor: 5.917
Authors: Philip J Law; Maria Timofeeva; Ceres Fernandez-Rozadilla; Peter Broderick; James Studd; Juan Fernandez-Tajes; Susan Farrington; Victoria Svinti; Claire Palles; Giulia Orlando; Amit Sud; Amy Holroyd; Steven Penegar; Evropi Theodoratou; Peter Vaughan-Shaw; Harry Campbell; Lina Zgaga; Caroline Hayward; Archie Campbell; Sarah Harris; Ian J Deary; John Starr; Laura Gatcombe; Maria Pinna; Sarah Briggs; Lynn Martin; Emma Jaeger; Archana Sharma-Oates; James East; Simon Leedham; Roland Arnold; Elaine Johnstone; Haitao Wang; David Kerr; Rachel Kerr; Tim Maughan; Richard Kaplan; Nada Al-Tassan; Kimmo Palin; Ulrika A Hänninen; Tatiana Cajuso; Tomas Tanskanen; Johanna Kondelin; Eevi Kaasinen; Antti-Pekka Sarin; Johan G Eriksson; Harri Rissanen; Paul Knekt; Eero Pukkala; Pekka Jousilahti; Veikko Salomaa; Samuli Ripatti; Aarno Palotie; Laura Renkonen-Sinisalo; Anna Lepistö; Jan Böhm; Jukka-Pekka Mecklin; Daniel D Buchanan; Aung-Ko Win; John Hopper; Mark E Jenkins; Noralane M Lindor; Polly A Newcomb; Steven Gallinger; David Duggan; Graham Casey; Per Hoffmann; Markus M Nöthen; Karl-Heinz Jöckel; Douglas F Easton; Paul D P Pharoah; Julian Peto; Federico Canzian; Anthony Swerdlow; Rosalind A Eeles; Zsofia Kote-Jarai; Kenneth Muir; Nora Pashayan; Andrea Harkin; Karen Allan; John McQueen; James Paul; Timothy Iveson; Mark Saunders; Katja Butterbach; Jenny Chang-Claude; Michael Hoffmeister; Hermann Brenner; Iva Kirac; Petar Matošević; Philipp Hofer; Stefanie Brezina; Andrea Gsur; Jeremy P Cheadle; Lauri A Aaltonen; Ian Tomlinson; Richard S Houlston; Malcolm G Dunlop Journal: Nat Commun Date: 2019-05-14 Impact factor: 14.919
Authors: Shane McCarthy; Sayantan Das; Warren Kretzschmar; Olivier Delaneau; Andrew R Wood; Alexander Teumer; Hyun Min Kang; Christian Fuchsberger; Petr Danecek; Kevin Sharp; Yang Luo; Carlo Sidore; Alan Kwong; Nicholas Timpson; Seppo Koskinen; Scott Vrieze; Laura J Scott; He Zhang; Anubha Mahajan; Jan Veldink; Ulrike Peters; Carlos Pato; Cornelia M van Duijn; Christopher E Gillies; Ilaria Gandin; Massimo Mezzavilla; Arthur Gilly; Massimiliano Cocca; Michela Traglia; Andrea Angius; Jeffrey C Barrett; Dorrett Boomsma; Kari Branham; Gerome Breen; Chad M Brummett; Fabio Busonero; Harry Campbell; Andrew Chan; Sai Chen; Emily Chew; Francis S Collins; Laura J Corbin; George Davey Smith; George Dedoussis; Marcus Dorr; Aliki-Eleni Farmaki; Luigi Ferrucci; Lukas Forer; Ross M Fraser; Stacey Gabriel; Shawn Levy; Leif Groop; Tabitha Harrison; Andrew Hattersley; Oddgeir L Holmen; Kristian Hveem; Matthias Kretzler; James C Lee; Matt McGue; Thomas Meitinger; David Melzer; Josine L Min; Karen L Mohlke; John B Vincent; Matthias Nauck; Deborah Nickerson; Aarno Palotie; Michele Pato; Nicola Pirastu; Melvin McInnis; J Brent Richards; Cinzia Sala; Veikko Salomaa; David Schlessinger; Sebastian Schoenherr; P Eline Slagboom; Kerrin Small; Timothy Spector; Dwight Stambolian; Marcus Tuke; Jaakko Tuomilehto; Leonard H Van den Berg; Wouter Van Rheenen; Uwe Volker; Cisca Wijmenga; Daniela Toniolo; Eleftheria Zeggini; Paolo Gasparini; Matthew G Sampson; James F Wilson; Timothy Frayling; Paul I W de Bakker; Morris A Swertz; Steven McCarroll; Charles Kooperberg; Annelot Dekker; David Altshuler; Cristen Willer; William Iacono; Samuli Ripatti; Nicole Soranzo; Klaudia Walter; Anand Swaroop; Francesco Cucca; Carl A Anderson; Richard M Myers; Michael Boehnke; Mark I McCarthy; Richard Durbin Journal: Nat Genet Date: 2016-08-22 Impact factor: 38.330
Authors: Nicola Whiffin; Fay J Hosking; Susan M Farrington; Claire Palles; Sara E Dobbins; Lina Zgaga; Amy Lloyd; Ben Kinnersley; Maggie Gorman; Albert Tenesa; Peter Broderick; Yufei Wang; Ella Barclay; Caroline Hayward; Lynn Martin; Daniel D Buchanan; Aung Ko Win; John Hopper; Mark Jenkins; Noralane M Lindor; Polly A Newcomb; Steve Gallinger; David Conti; Fred Schumacher; Graham Casey; Tao Liu; Harry Campbell; Annika Lindblom; Richard S Houlston; Ian P Tomlinson; Malcolm G Dunlop Journal: Hum Mol Genet Date: 2014-04-15 Impact factor: 6.150