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

By Louise Wang, Heena Desai, Shefali S. Verma, Anh Le, Ryan Hausler, Anurag Verma, Renae Judy, Abigail Doucette, Peter E. Gabriel, Regeneron Genetics Center, Katherine L Nathanson, Scott Damrauer, Danielle L. Mowery, Marylyn D. Ritchie, Rachel L. Kember, Kara N Maxwell

Posted 19 May 2021
medRxiv DOI: 10.1101/2021.05.13.21256833

Purpose: Genome-wide association studies (GWAS) have identified hundreds of single nucleotide polymorphisms (SNPs) significantly associated with several cancers, but the predictive ability of polygenic risk scores (PRS) derived from multiple variants is unclear for many cancers, especially among non-European populations. Methods: Genome wide genotype data was available for 20,079 individuals enrolled in an academic biobank. PRS were derived from significant DNA variants for 15 cancers. Logistic regression was used to determine the discriminatory accuracy of each cancer-specific PRS in patients of genetically determined African and European ancestry separately. Results: Among European individuals, four PRS were significantly associated with their respective cancers (breast, colon, melanoma, and prostate), with an OR ranging from 1.25-1.47. Among African individuals, PRS for breast, colon, and prostate were significantly associated with their respective cancers. The discriminatory ability of a model comprised of age, sex, and principal components was 0.617-0.709, and the AUC increased by 1-4% with the addition of the PRS in Europeans. AUC was overall higher in the full model including PRS (AUC 0.742-0.818) in African individuals, but the PRS increased the AUC by less than 1% in the majority of cancers in African individuals. Conclusion: PRS constructed from SNPs moderately increased discriminatory ability for cancer status over age, sex, and nonspecific genetic factors in individuals of European but not African ancestry. Further large-scale studies are needed to identify ancestry-specific genetic factors for cancer risk in non-European populations to incorporate PRS into cancer risk assessment.

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