Zhaohui Du1,2, Guimin Gao3, Babatunde Adedokun3, Thomas Ahearn4, Kathryn L Lunetta5, Gary Zirpoli6, Melissa A Troester7, Edward A Ruiz-Narváez6, Stephen A Haddad6, Parichoy PalChoudhury4, Jonine Figueroa4,8,9, Esther M John10,11, Leslie Bernstein12, Wei Zheng13, Jennifer J Hu14, Regina G Ziegler4, Sarah Nyante15, Elisa V Bandera16, Sue A Ingles1, Nicholas Mancuso1, Michael F Press17, Sandra L Deming13, Jorge L Rodriguez-Gil18,19, Song Yao20, Temidayo O Ogundiran21, Oladosu Ojengbe22, Manjeet K Bolla23, Joe Dennis23, Alison M Dunning24, Douglas F Easton24, Kyriaki Michailidou25, Paul D P Pharoah24, Dale P Sandler26, Jack A Taylor26, Qin Wang23, Clarice R Weinberg27, Cari M Kitahara28, William Blot13,29, Katherine L Nathanson30, Anselm Hennis31, Barbara Nemesure32, Stefan Ambs33, Lara E Sucheston-Campbell34,35, Jeannette T Bensen7, Stephen J Chanock4, Andrew F Olshan36, Christine B Ambrosone20, Olufunmilayo I Olopade37, Joel Yarney38, Baffour Awuah39, Beatrice Wiafe-Addai40, David V Conti, Julie R Palmer6, Montserrat Garcia-Closas4, Dezheng Huo3, Christopher A Haiman1. 1. Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA. 2. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 3. Department of Public Health Sciences, University of Chicago, Chicago, IL, USA. 4. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 5. Department of Biostatistics, Boston University, Boston, MA, USA. 6. Slone Epidemiology Center, Boston University, Boston, MA, USA. 7. Department of Epidemiology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 8. Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK. 9. Cancer Research UK Edinburgh Centre, Edinburgh, UK. 10. Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA. 11. Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA, USA. 12. Division of Biomarkers of Early Detection and Prevention Department of Population Sciences, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Los Angeles, CA, USA. 13. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA. 14. Department of Public Health Sciences, Sylvester Comprehensive Cancer Center University of Miami Miller School of Medicine, Miami, FL, USA. 15. Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. 16. Department of Population Science, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. 17. Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. 18. Genomics, Development and Disease Section, Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. 19. Medical Scientist Training Program, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA. 20. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA. 21. Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria. 22. Center for Population and Reproductive Health, College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria. 23. Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. 24. Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. 25. Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus. 26. Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. 27. Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. 28. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. 29. International Epidemiology Institute, Rockville, MD, USA. 30. Department of Medicine, Abramson Cancer Center, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 31. Chronic Disease Research Centre and Faculty of Medical Sciences, University of the West Indies, Bridgetown, Barbados. 32. Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, USA. 33. Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. 34. College of Pharmacy, The Ohio State University, Columbus, OH, USA. 35. College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA. 36. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. 37. Department of Medicine, Center for Clinical Cancer Genetics and Global Health, University of Chicago, Chicago, IL, USA. 38. Korle Bu Teaching Hospital, Accra, Ghana. 39. Komfo Anoyke Teaching Hospital, Kumasi, Ghana. 40. Peace and Love Hospital, Kumasi, Ghana.
Abstract
BACKGROUND: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. METHODS: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category. RESULTS: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. CONCLUSION: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.
BACKGROUND: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. METHODS: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category. RESULTS: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. CONCLUSION: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.
Authors: Inge M M Lakeman; Florentine S Hilbers; Mar Rodríguez-Girondo; Andrew Lee; Maaike P G Vreeswijk; Antoinette Hollestelle; Caroline Seynaeve; Hanne Meijers-Heijboer; Jan C Oosterwijk; Nicoline Hoogerbrugge; Edith Olah; Hans F A Vasen; Christi J van Asperen; Peter Devilee Journal: J Med Genet Date: 2019-06-11 Impact factor: 6.318
Authors: Amber N Hurson; Parichoy Pal Choudhury; Chi Gao; Anika Hüsing; Mikael Eriksson; Min Shi; Michael E Jones; D Gareth R Evans; Roger L Milne; Mia M Gaudet; Celine M Vachon; Daniel I Chasman; Douglas F Easton; Marjanka K Schmidt; Peter Kraft; Montserrat Garcia-Closas; Nilanjan Chatterjee Journal: Int J Epidemiol Date: 2021-03-23 Impact factor: 9.685
Authors: Fang Chen; Gary K Chen; Daniel O Stram; Robert C Millikan; Christine B Ambrosone; Esther M John; Leslie Bernstein; Wei Zheng; Julie R Palmer; Jennifer J Hu; Tim R Rebbeck; Regina G Ziegler; Sarah Nyante; Elisa V Bandera; Sue A Ingles; Michael F Press; Edward A Ruiz-Narvaez; Sandra L Deming; Jorge L Rodriguez-Gil; Angela Demichele; Stephen J Chanock; William Blot; Lisa Signorello; Qiuyin Cai; Guoliang Li; Jirong Long; Dezheng Huo; Yonglan Zheng; Nancy J Cox; Olufunmilayo I Olopade; Temidayo O Ogundiran; Clement Adebamowo; Katherine L Nathanson; Susan M Domchek; Michael S Simon; Anselm Hennis; Barbara Nemesure; Suh-Yuh Wu; M Cristina Leske; Stefan Ambs; Carolyn M Hutter; Alicia Young; Charles Kooperberg; Ulrike Peters; Suhn K Rhie; Peggy Wan; Xin Sheng; Loreall C Pooler; David J Van Den Berg; Loic Le Marchand; Laurence N Kolonel; Brian E Henderson; Christopher A Haiman Journal: Hum Genet Date: 2012-08-25 Impact factor: 4.132
Authors: Wanqing Wen; Xiao-Ou Shu; Xingyi Guo; Qiuyin Cai; Jirong Long; Manjeet K Bolla; Kyriaki Michailidou; Joe Dennis; Qin Wang; Yu-Tang Gao; Ying Zheng; Alison M Dunning; Montserrat García-Closas; Paul Brennan; Shou-Tung Chen; Ji-Yeob Choi; Mikael Hartman; Hidemi Ito; Artitaya Lophatananon; Keitaro Matsuo; Hui Miao; Kenneth Muir; Suleeporn Sangrajrang; Chen-Yang Shen; Soo H Teo; Chiu-Chen Tseng; Anna H Wu; Cheng Har Yip; Jacques Simard; Paul D P Pharoah; Per Hall; Daehee Kang; Yongbing Xiang; Douglas F Easton; Wei Zheng Journal: Breast Cancer Res Date: 2016-12-08 Impact factor: 6.466
Authors: Nasim Mavaddat; Kyriaki Michailidou; Joe Dennis; Michael Lush; Laura Fachal; Andrew Lee; Jonathan P Tyrer; Ting-Huei Chen; Qin Wang; Manjeet K Bolla; Xin Yang; Muriel A Adank; Thomas Ahearn; Kristiina Aittomäki; Jamie Allen; Irene L Andrulis; Hoda Anton-Culver; Natalia N Antonenkova; Volker Arndt; Kristan J Aronson; Paul L Auer; Päivi Auvinen; Myrto Barrdahl; Laura E Beane Freeman; Matthias W Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Leslie Bernstein; Carl Blomqvist; Natalia V Bogdanova; Stig E Bojesen; Bernardo Bonanni; Anne-Lise Børresen-Dale; Hiltrud Brauch; Michael Bremer; Hermann Brenner; Adam Brentnall; Ian W Brock; Angela Brooks-Wilson; Sara Y Brucker; Thomas Brüning; Barbara Burwinkel; Daniele Campa; Brian D Carter; Jose E Castelao; Stephen J Chanock; Rowan Chlebowski; Hans Christiansen; Christine L Clarke; J Margriet Collée; Emilie Cordina-Duverger; Sten Cornelissen; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; Mary B Daly; Peter Devilee; Thilo Dörk; Isabel Dos-Santos-Silva; Martine Dumont; Lorraine Durcan; Miriam Dwek; Diana M Eccles; Arif B Ekici; A Heather Eliassen; Carolina Ellberg; Christoph Engel; Mikael Eriksson; D Gareth Evans; Peter A Fasching; Jonine Figueroa; Olivia Fletcher; Henrik Flyger; Asta Försti; Lin Fritschi; Marike Gabrielson; Manuela Gago-Dominguez; Susan M Gapstur; José A García-Sáenz; Mia M Gaudet; Vassilios Georgoulias; Graham G Giles; Irina R Gilyazova; Gord Glendon; Mark S Goldberg; David E Goldgar; Anna González-Neira; Grethe I Grenaker Alnæs; Mervi Grip; Jacek Gronwald; Anne Grundy; Pascal Guénel; Lothar Haeberle; Eric Hahnen; Christopher A Haiman; Niclas Håkansson; Ute Hamann; Susan E Hankinson; Elaine F Harkness; Steven N Hart; Wei He; Alexander Hein; Jane Heyworth; Peter Hillemanns; Antoinette Hollestelle; Maartje J Hooning; Robert N Hoover; John L Hopper; Anthony Howell; Guanmengqian Huang; Keith Humphreys; David J Hunter; Milena Jakimovska; Anna Jakubowska; Wolfgang Janni; Esther M John; Nichola Johnson; Michael E Jones; Arja Jukkola-Vuorinen; Audrey Jung; Rudolf Kaaks; Katarzyna Kaczmarek; Vesa Kataja; Renske Keeman; Michael J Kerin; Elza Khusnutdinova; Johanna I Kiiski; Julia A Knight; Yon-Dschun Ko; Veli-Matti Kosma; Stella Koutros; Vessela N Kristensen; Ute Krüger; Tabea Kühl; Diether Lambrechts; Loic Le Marchand; Eunjung Lee; Flavio Lejbkowicz; Jenna Lilyquist; Annika Lindblom; Sara Lindström; Jolanta Lissowska; Wing-Yee Lo; Sibylle Loibl; Jirong Long; Jan Lubiński; Michael P Lux; Robert J MacInnis; Tom Maishman; Enes Makalic; Ivana Maleva Kostovska; Arto Mannermaa; Siranoush Manoukian; Sara Margolin; John W M Martens; Maria Elena Martinez; Dimitrios Mavroudis; Catriona McLean; Alfons Meindl; Usha Menon; Pooja Middha; Nicola Miller; Fernando Moreno; Anna Marie Mulligan; Claire Mulot; Victor M Muñoz-Garzon; Susan L Neuhausen; Heli Nevanlinna; Patrick Neven; William G Newman; Sune F Nielsen; Børge G Nordestgaard; Aaron Norman; Kenneth Offit; Janet E Olson; Håkan Olsson; Nick Orr; V Shane Pankratz; Tjoung-Won Park-Simon; Jose I A Perez; Clara Pérez-Barrios; Paolo Peterlongo; Julian Peto; Mila Pinchev; Dijana Plaseska-Karanfilska; Eric C Polley; Ross Prentice; Nadege Presneau; Darya Prokofyeva; Kristen Purrington; Katri Pylkäs; Brigitte Rack; Paolo Radice; Rohini Rau-Murthy; Gad Rennert; Hedy S Rennert; Valerie Rhenius; Mark Robson; Atocha Romero; Kathryn J Ruddy; Matthias Ruebner; Emmanouil Saloustros; Dale P Sandler; Elinor J Sawyer; Daniel F Schmidt; Rita K Schmutzler; Andreas Schneeweiss; Minouk J Schoemaker; Fredrick Schumacher; Peter Schürmann; Lukas Schwentner; Christopher Scott; Rodney J Scott; Caroline Seynaeve; Mitul Shah; Mark E Sherman; Martha J Shrubsole; Xiao-Ou Shu; Susan Slager; Ann Smeets; Christof Sohn; Penny Soucy; Melissa C Southey; John J Spinelli; Christa Stegmaier; Jennifer Stone; Anthony J Swerdlow; Rulla M Tamimi; William J Tapper; Jack A Taylor; Mary Beth Terry; Kathrin Thöne; Rob A E M Tollenaar; Ian Tomlinson; Thérèse Truong; Maria Tzardi; Hans-Ulrich Ulmer; Michael Untch; Celine M Vachon; Elke M van Veen; Joseph Vijai; Clarice R Weinberg; Camilla Wendt; Alice S Whittemore; Hans Wildiers; Walter Willett; Robert Winqvist; Alicja Wolk; Xiaohong R Yang; Drakoulis Yannoukakos; Yan Zhang; Wei Zheng; Argyrios Ziogas; Alison M Dunning; Deborah J Thompson; Georgia Chenevix-Trench; Jenny Chang-Claude; Marjanka K Schmidt; Per Hall; Roger L Milne; Paul D P Pharoah; Antonis C Antoniou; Nilanjan Chatterjee; Peter Kraft; Montserrat García-Closas; Jacques Simard; Douglas F Easton Journal: Am J Hum Genet Date: 2018-12-13 Impact factor: 11.025
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