Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry-Reference-Cited by-同舟云学术

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry

Published:2021-03-26 Issue:9 Volume:113 Page:1168-1176
ISSN:0027-8874
Container-title:JNCI: Journal of the National Cancer Institute
language:en
Short-container-title:

Author:

Du Zhaohui¹²,Gao Guimin³,Adedokun Babatunde³,Ahearn Thomas⁴^ORCID,Lunetta Kathryn L⁵^ORCID,Zirpoli Gary⁶^ORCID,Troester Melissa A⁷,Ruiz-Narváez Edward A⁶,Haddad Stephen A⁶,PalChoudhury Parichoy⁴,Figueroa Jonine⁴⁸⁹^ORCID,John Esther M¹⁰¹¹,Bernstein Leslie¹²^ORCID,Zheng Wei¹³,Hu Jennifer J¹⁴^ORCID,Ziegler Regina G⁴^ORCID,Nyante Sarah¹⁵^ORCID,Bandera Elisa V¹⁶,Ingles Sue A¹^ORCID,Mancuso Nicholas¹,Press Michael F¹⁷^ORCID,Deming Sandra L¹³,Rodriguez-Gil Jorge L¹⁸¹⁹^ORCID,Yao Song²⁰^ORCID,Ogundiran Temidayo O²¹^ORCID,Ojengbe Oladosu²²,Bolla Manjeet K²³,Dennis Joe²³^ORCID,Dunning Alison M²⁴^ORCID,Easton Douglas F²⁴^ORCID,Michailidou Kyriaki²⁵^ORCID,Pharoah Paul D P²⁴^ORCID,Sandler Dale P²⁶^ORCID,Taylor Jack A²⁶^ORCID,Wang Qin²³^ORCID,Weinberg Clarice R²⁷,Kitahara Cari M²⁸^ORCID,Blot William¹³²⁹,Nathanson Katherine L³⁰^ORCID,Hennis Anselm³¹,Nemesure Barbara³²,Ambs Stefan³³^ORCID,Sucheston-Campbell Lara E³⁴³⁵,Bensen Jeannette T⁷,Chanock Stephen J⁴,Olshan Andrew F³⁶,Ambrosone Christine B²⁰^ORCID,Olopade Olufunmilayo I³⁷,Yarney Joel³⁸,Awuah Baffour³⁹,Wiafe-Addai Beatrice⁴⁰,Conti David V,Palmer Julie R⁶^ORCID,Garcia-Closas Montserrat⁴^ORCID,Huo Dezheng³^ORCID,Haiman Christopher A¹,

Affiliation:

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

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.

Funder

NIH

US National Cancer Institute

National Institutes of Health

Research Program and NCI

PERSPECTIVE

Government of Canada through Genome Canada and the Canadian Institutes of Health Research

Genome Québec

Quebec Breast Cancer Foundation

NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and Discovery, Biology and Risk of Inherited Variants in Breast Cancer

NIH Grants

Cancer Research UK