1. Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry
- Author
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Joe Dennis, Beatrice Wiafe-Addai, Nicholas Mancuso, Cari M. Kitahara, David V. Conti, Qin Wang, Andrew F. Olshan, Katherine L. Nathanson, Lara E. Sucheston-Campbell, Jonine D. Figueroa, Manjeet K. Bolla, William J. Blot, Song Yao, Thomas U. Ahearn, Dezheng Huo, Michael F. Press, Julie R. Palmer, Jorge L Rodriguez-Gil, Oladosu Ojengbe, Sandra L. Deming, Sarah J. Nyante, Stephen J. Chanock, Joel Yarney, Douglas F. Easton, Jack A. Taylor, Wei Zheng, Dale P. Sandler, Regina G. Ziegler, Christine B. Ambrosone, Gary Zirpoli, Melissa A. Troester, Anselm Hennis, Olufunmilayo I. Olopade, Jeannette T. Bensen, Babatunde Adedokun, Christopher A. Haiman, Paul D.P. Pharoah, Leslie Bernstein, Barbara Nemesure, Elisa V. Bandera, Stephen A. Haddad, Baffour Awuah, Clarice R. Weinberg, Kyriaki Michailidou, Guimin Gao, Stefan Ambs, Sue A. Ingles, Montserrat Garcia-Closas, Edward A. Ruiz-Narváez, Zhaohui Du, Temidayo O. Ogundiran, Jennifer J. Hu, Kathryn L. Lunetta, Alison M. Dunning, Parichoy PalChoudhury, and Esther M. John
- Subjects
Cancer Research ,Percentile ,Black People ,Breast Neoplasms ,Decile ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Asian People ,Risk Factors ,medicine ,Humans ,Genetic Predisposition to Disease ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,Receiver operating characteristic ,business.industry ,Absolute risk reduction ,Odds ratio ,medicine.disease ,Confidence interval ,Oncology ,030220 oncology & carcinogenesis ,Polygenic risk score ,Female ,business ,Demography - 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.
- Published
- 2020