Dataset Information

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

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.

SUBMITTER: Du Z

PROVIDER: S-EPMC8418423 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Du Zhaohui Z Gao Guimin G Adedokun Babatunde B Ahearn Thomas T Lunetta Kathryn L KL Zirpoli Gary G Troester Melissa A MA Ruiz-Narváez Edward A EA Haddad Stephen A SA PalChoudhury Parichoy P Figueroa Jonine J John Esther M EM Bernstein Leslie L Zheng Wei W Hu Jennifer J JJ Ziegler Regina G RG Nyante Sarah S Bandera Elisa V EV Ingles Sue A SA Mancuso Nicholas N Press Michael F MF Deming Sandra L SL Rodriguez-Gil Jorge L JL Yao Song S Ogundiran Temidayo O TO Ojengbe Oladosu O Bolla Manjeet K MK Dennis Joe J Dunning Alison M AM Easton Douglas F DF Michailidou Kyriaki K Pharoah Paul D P PDP Sandler Dale P DP Taylor Jack A JA Wang Qin Q Weinberg Clarice R CR Kitahara Cari M CM Blot William W Nathanson Katherine L KL Hennis Anselm A Nemesure Barbara B Ambs Stefan S Sucheston-Campbell Lara E LE Bensen Jeannette T JT Chanock Stephen J SJ Olshan Andrew F AF Ambrosone Christine B CB Olopade Olufunmilayo I OI Yarney Joel J Awuah Baffour B Wiafe-Addai Beatrice B Conti David V DV Palmer Julie R JR Garcia-Closas Montserrat M Huo Dezheng D Haiman Christopher A CA

Journal of the National Cancer Institute 20210901 9

<h4>Background</h4>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.<h4>Methods</h4>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 a ...[more]

PMID: 33769540

Similar Datasets

Project description:ImportanceMultiple polygenic risk scores (PRSs) for breast cancer have been developed from large research consortia; however, their generalizability to diverse clinical settings is unknown.ObjectiveTo examine the performance of previously developed breast cancer PRSs in a clinical setting for women of European, African, and Latinx ancestry.Design, setting, and participantsThis cohort study using the Electronic Medical Records and Genomics (eMERGE) network data set included 39 591 women from 9 contributing medical centers in the US that had electronic medical records (EMR) linked to genotype data. Breast cancer cases and controls were identified through a validated EMR phenotyping algorithm.Main outcomes and measuresMultivariable logistic regression was used to assess the association between breast cancer risk and 7 previously developed PRSs, adjusting for age, study site, breast cancer family history, and first 3 ancestry informative principal components.ResultsThis study included 39 591 women: 33 594 with European, 3801 with African, and 2196 with Latinx ancestry. The mean (SD) age at breast cancer diagnosis was 60.7 (13.0), 58.8 (12.5), and 60.1 (13.0) years for women with European, African, and Latinx ancestry, respectively. PRSs derived from women with European ancestry were associated with breast cancer risk in women with European ancestry (highest odds ratio [OR] per 1-SD increase, 1.46; 95% CI, 1.41-1.51), women with Latinx ancestry (highest OR, 1.31; 95% CI, 1.09-1.58), and women with African ancestry (OR, 1.19; 95% CI, 1.05-1.35). For women with European ancestry, this association with breast cancer risk was largest in the extremes of the PRS distribution, with ORs ranging from 2.19 (95% CI, 1.84-2.53) to 2.48 (95% CI, 1.89-3.25) for the 3 different PRSs examined for those in the highest 1% of the PRS compared with those in the middle quantile. Among women with Latinx and African ancestries at the extremes of the PRS distribution, there were no statistically significant associations.Conclusions and relevanceThis cohort study found that PRS models derived from women with European ancestry for breast cancer risk generalized well for women with European, Latinx, and African ancestries across different clinical settings, although the effect sizes for women with African ancestry were smaller, likely because of differences in risk allele frequencies and linkage disequilibrium patterns. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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