Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar;24(3):601-609.
doi: 10.1016/j.gim.2021.10.015. Epub 2021 Nov 30.

Performance of polygenic risk scores for cancer prediction in a racially diverse academic biobank

Louise Wang  1 , Heena Desai  2 , Shefali S Verma  3 , Anh Le  2 , Ryan Hausler  2 , Anurag Verma  3 , Renae Judy  4 , Abigail Doucette  5 , Peter E Gabriel  6 ; Regeneron Genetics Center; Katherine L Nathanson  7 , Scott M Damrauer  8 , Danielle L Mowery  9 , Marylyn D Ritchie  3 , Rachel L Kember  10 , Kara N Maxwell  11
Collaborators, Affiliations

Performance of polygenic risk scores for cancer prediction in a racially diverse academic biobank

Louise Wang et al. Genet Med. 2022 Mar.

Abstract

Purpose: Genome-wide association studies have identified hundreds of single nucleotide variations (formerly single nucleotide polymorphisms) associated with several cancers, but the predictive ability of polygenic risk scores (PRSs) is unclear, especially among non-Whites.

Methods: PRSs were derived from genome-wide significant single-nucleotide variations for 15 cancers in 20,079 individuals in an academic biobank. We evaluated the improvement in discriminatory accuracy by including cancer-specific PRS in patients of genetically-determined African and European ancestry.

Results: Among the individuals of European genetic ancestry, PRSs for breast, colon, melanoma, and prostate were significantly associated with their respective cancers. Among the individuals of African genetic ancestry, PRSs for breast, colon, prostate, and thyroid were significantly associated with their respective cancers. The area under the curve of the model consisting of age, sex, and principal components was 0.621 to 0.710, and it increased by 1% to 4% with the inclusion of PRS in individuals of European genetic ancestry. In individuals of African genetic ancestry, area under the curve was overall higher in the model without the PRS (0.723-0.810) but increased by <1% with the inclusion of PRS for most cancers.

Conclusion: PRS moderately increased the ability to discriminate the cancer status in individuals of European but not African ancestry. Further large-scale studies are needed to identify ancestry-specific genetic factors in non-White populations to incorporate PRS into cancer risk assessment.

Keywords: Cancer risk; GWAS; PRS; Polygenic risk score; Racial differences.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest S.M.D. receives research support to the University of Pennsylvania from RenalytixAI and consulting fees from Calico Labs, both outside the current work. S.M.D. is named as a coinventor on a Government-owned US Patent application related to the use of genetic risk prediction for venous thromboembolic disease filed by the US Department of Veterans Affairs in accordance with Federal regulatory requirements. M.D.R. is on the scientific advisory board for Goldfinch Bio and Cipherome. The remaining authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Association of PRS with cancer in individuals of genetically determined African ancestry and European ancestry in academic biobank.
Forest plots show the ORs for cancers with >100 cases of genetically determined European ancestry (breast, bladder, colorectal, lung, melanoma, renal, prostate, and thyroid cancers) and African ancestry (breast, colorectal, lung, renal, prostate, and thyroid cancers). ORs are displayed as associations per SD of PRS. Breast-313, Prostate-AFR and Prostate-EUR use SNVs from previously validated PRS., AFR, African genetic ancestry; CRC, colorectal cancer; EUR, European genetic ancestry; OR, odds ratio; PRS, polygenic risk scores; SNV, single-nucleotide variation.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. 10.3322/caac.21590. - DOI - PubMed
    1. Yanes T, Young MA, Meiser B, James PA. Clinical applications of polygenic breast cancer risk: a critical review and perspectives of an emerging field. Breast Cancer Res. 2020;22(1):21. 10.1186/s13058-020-01260-3. - DOI - PMC - PubMed
    1. Zheng Y, Hua X, Win AK, et al. A new comprehensive colorectal cancer risk prediction model incorporating family history, personal characteristics, and environmental factors. Cancer Epidemiol Biomarkers Prev. 2020;29(3):549–557. 10.1158/1055-9965.EPI-19-0929. - DOI - PMC - PubMed
    1. Carver T, Hartley S, Lee A, et al. CanRisk tool-A web interface for the prediction of breast and ovarian cancer risk and the likelihood of carrying genetic pathogenic variants. Cancer Epidemiol Biomarkers Prev. 2021;30(3):469–473. 10.1158/1055-9965.EPI-20-1319. - DOI - PMC - PubMed
    1. Lee A, Mavaddat N, Wilcox AN, et al. BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors. Genet Med. 2019;21(8):1708–1718. Published correction appears in Genet Med. 2019;21(6):1462. 10.1038/s41436-018-0406-9. - DOI - PMC - PubMed

Publication types