Faculty, Staff and Student Publications

Publication Date

5-1-2024

Journal

Nature Genetics

DOI

10.1038/s41588-024-01736-4

PMID

38741014

PMCID

PMC11284829

PubMedCentral® Posted Date

5-13-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10-8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66-7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

Keywords

Humans, Female, Genome-Wide Association Study, Genetic Predisposition to Disease, Breast Neoplasms, Polymorphism, Single Nucleotide, Black People, Case-Control Studies, Risk Factors, Triple Negative Breast Neoplasms, Alleles, Multifactorial Inheritance, Middle Aged, Genetic Loci, White People

Published Open-Access

yes

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