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


Du, Zhaohui; Gao, Guimin; Adedokun, Babatunde; Ahearn, Thomas; Lunetta, Kathryn L.; Zirpoli, Gary R.; Troester, Melissa A.; Ruiz-Narváez, Edward A.; Haddad, Stephen A.; & Pal Choudhury, Parichoy, et al. (Online ahead of print). Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry. Journal of the National Cancer Institute. PMCID: PMC Journal - In Process


BACKGROUND: Polygenic risk scores (PRS) 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 9,241 cases and 10,193 controls. 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 (AUC). 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 ratios per standard deviation of PRS313 was 1.27 (95%CI = 1.23 to 1.31), with an AUC of 0.571 (95%CI = 0.562 to 0.579). Compared to 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 to 1.72). 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 to that reported in European, Asian and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.


Reference Type

Journal Article

Article Type


Year Published

Online ahead of print

Journal Title

Journal of the National Cancer Institute


Du, Zhaohui
Gao, Guimin
Adedokun, Babatunde
Ahearn, Thomas
Lunetta, Kathryn L.
Zirpoli, Gary R.
Troester, Melissa A.
Ruiz-Narváez, Edward A.
Haddad, Stephen A.
Pal Choudhury, Parichoy
Figueroa, Jonine
John, Esther M.
Bernstein, Leslie
Zheng, Wei
Hu, Jennifer J.
Ziegler, Regina G.
Nyante, Sarah J.
Bandera, Elisa V.
Ingles, Sue A.
Mancuso, Nicholas
Press, Michael F.
Deming, Sandra L.
Rodriguez-Gil, Jorge L.
Yao, Song
Ogundiran, Temidayo O.
Ojengbe, Oladosu
Bolla, Manjeet K.
Dennis, Joe
Dunning, Alison M.
Easton, Douglas F.
Michailidou, Kyriaki
Pharoah, Paul D. P.
Sandler, Dale P.
Taylor, Jack A.
Wang, Qin
Weinberg, Clarice R.
Kitahara, Cari M.
Blot, William J.
Nathanson, Katherine L.
Hennis, Anselm J.
Nemesure, Barbara
Ambs, Stefan
Sucheston-Campbell, Lara E.
Bensen, Jeannette T.
Chanock, Stephen J.
Olshan, Andrew F.
Ambrosone, Christine B.
Olopade, Olufunmilayo I.
Yarney, Joel
Awuah, Baffour
Addai Wiafe, Beatrice
Conti, David V.
GBHS Study Team,
Palmer, Julie R.
Garcia-Closas, Montserrat
Huo, Dezheng
Haiman, Christopher A.


PMC Journal - In Process

Data Set/Study

African American Breast Cancer Consortium (AABC)
African American Breast Cancer Epidemiology and Risk (AMBER) Consortium
Breast Cancer Association Consortium (BCAC)
GAME-ON OncoArray consortium (ONCO)
GWAS of Breast Cancer in the African Diaspora consortium (ROOT)
Ghana Breast Health Study (GBHS)




European Ancestry
African Ancestry