. 2021 Sep 4;113(9):1168-1176.

doi: 10.1093/jnci/djab050.

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

Zhaohui Du^{1

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 Figueroa^{4

8

9}, Esther M John^{10

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-Gil^{18

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 Blot^{13

29}, Katherine L Nathanson³⁰, Anselm Hennis³¹, Barbara Nemesure³², Stefan Ambs³³, Lara E Sucheston-Campbell^{34

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; GBHS Study Team; Julie R Palmer⁶, Montserrat Garcia-Closas⁴, Dezheng Huo³, Christopher A Haiman¹

Affiliations

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.

PMID: 33769540
PMCID: PMC8418423
DOI: 10.1093/jnci/djab050

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

Zhaohui Du et al. J Natl Cancer Inst. 2021.

. 2021 Sep 4;113(9):1168-1176.

doi: 10.1093/jnci/djab050.

Authors

Affiliations

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.

PMID: 33769540
PMCID: PMC8418423
DOI: 10.1093/jnci/djab050

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.

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Figures

**Figure 1.**
Association between the categorical 313-variant polygenic risk score (PRS₃₁₃) and overall breast cancer risk by population. The **x-axis** indicates the PRS₃₁₃ percentiles. The **y-axis** represents odds ratio (OR) values for the indicated PRS₃₁₃ percentiles compared with the 40%-60% category of PRS₃₁₃ as the reference (population average risk). **Dots** represent odds ratios and **error bar lines** represent standard error estimated in each population. The **grey line** represents results for women of African ancestry, which were estimated in this study. The **yellow line** represents results for Latinas obtained from a previous Latino PRS study (10). The **blue line** represents results for Asian women obtained from an Asian PRS study (18). The **green line** represents results for women of European ancestry obtained from a previous European ancestry PRS study (6). African ancestry results are also provided in Table 1.

**Figure 2.**
Lifetime absolute risk of breast cancer by polygenic risk score (PRS) category in African American women. Lifetime absolute risk of developing breast cancer for the 313-variant PRS (PRS₃₁₃) in African American women for overall breast cancer (A), estrogen receptor (ER)-positive breast cancer (B) and ER-negative breast cancer (C) and in European-ancestry women for overall breast cancer (D), ER-positive breast cancer (E), and ER-negative breast cancer (F). The **x-axis** represents age and the **y-axis** is the absolute risk of breast cancer by a given age. The **different colored lines** represent the corresponding PRS strata. See Methods for details about the calculation of absolute risks.

See this image and copyright information in PMC

Comment in

Do Breast Cancer Risk Scores Work for You?
Houlahan KE. Houlahan KE. J Natl Cancer Inst. 2021 Sep 4;113(9):1118-1119. doi: 10.1093/jnci/djab052. J Natl Cancer Inst. 2021. PMID: 33769538 No abstract available.

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

Affiliations

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

Authors

Affiliations

Abstract

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Full Text Sources

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