In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 2320-2320
Abstract:
Background: A polygenic risk score (PRS) for breast cancer including 313 common variants developed by the Breast Cancer Association Consortium (BCAC) has been demonstrated to identify women who are at high risk of developing breast cancer [odds ratio (OR 95%CI) = 1.61 (1.57-1.65) per SD] in women of European ancestry. In the present study, we examined the performance of the 313-variant PRS and a PRS including 179 variants reaching genome-wide significance in previous genome-wide association studies (GWAS), in women of African ancestry. Methods: We assembled genotype data for women of African ancestry from 28 breast cancer studies, including a total of 9,241 cases and 10,193 controls. We constructed the 179-variant and 313-variant PRSs with relative risk weights for each variant estimated in women of European ancestry in BCAC. The associations between the two PRSs and overall, ER+ and ER- breast cancer risk were estimated using logistic regression adjusting for age, study site and principal components. Discriminatory accuracy of the PRSs was evaluated using the receiver operating characteristic curve (AUROC). We then recalibrated the 179-variant PRS by replacing index variants with variants in each region that better captured risk in women of African ancestry and used relative risk weights estimated in women of African ancestry. We also assessed PRS performance by age ( & lt;55 versus ≥ 55 years). Results: Both the 179 and 313- variant PRSs were significantly associated with overall, ER+ and ER- breast cancer risk, with odds ratios (OR) per standard deviation of 1.21~1.37 and AUROCs ranging from 0.57 to 0.59. The 179-variant PRS outperformed in ER- cancer [1.31(1.24,1.37) per SD] while the 313-SNP PRS was better for overall [1.27(1.23,1.31) per SD] and ER+ cancer [1.37(1.32,1.43) per SD]. For overall breast cancer, compared to women with average risk (40th-60th PRS percentiles), women in the top decile of PRS had a 1.54 (95% CI: 1.38, 1.72)-fold increased risk. The performance of the recalibrated 179-variant PRS was not improved (average AUROC=0.56). The PRS ORs did not differ significantly across age strata (P-value for age interaction = 0.63). Conclusion: Our study shows that both 179 and 313 variant PRS stratify breast cancer risk in women of African ancestry, with attenuated performance compared to that reported in European and in Latina populations. Future work is needed to improve breast cancer risk stratification for women of African ancestry. Citation Format: Zhaohui Du, Guimin Gao, Babatunde Adedokun, Thomas Ahearn, Kathryn L. Lunetta, Gary Zirpoli, Melissa Troester, Edward A. Ruiz-Narváez, Stephen Haddad, Jonine Figueroa, Esther M. John, Leslie Bernstein, Wei Zheng, Jennifer J. Hu, Regina G. Ziegler, Sarah Nyante, Elisa V. Bandera, Sue A. Ingles, Michael F. Press, Sandra L. Deming, Jorge L. Rodriguez-Gil, Song Yao, Temidayo O. Ogundiran, Oladosu A. Ojengbede, William Blot, Katherine L. Nathanson, Anselm Hennis, Barbara Nemesure, Stefan Ambs, Lara E. Sucheston-Campbell, Jeannette T. Bensen, Stephen J. Chanock, Andrew F. Olshan, Christine B. Ambrosone, David V. Conti, Olufunmilayo I. Olopade, Julie R. Palmer, Montserrat Garcia-Closas, Dezheng Huo, Christopher A. Haiman. Evaluating a polygenic risk score for breast cancer in women of African ancestry [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2320.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2020-2320
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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