African American Women
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Researchers from the Vanderbilt-Ingram Cancer Center identified new genome-wide gene variants at 12 different locations associated with breast cancer in women of African ancestry. They discovered that variants in three of the 12 were associated with triple-negative breast cancer (TNBC).

Historically, women of African ancestry have been largely underrepresented in studies of germline susceptibility to cancer. This study, published in Nature Genetics, is the largest GWAS for breast cancer in this population. The team analyzed the genome of 18,034 women of African ancestry with breast cancer and 22,104 controls. Slightly more than 85 percent of the women in the study were from the U.S. with 14.7 percent from the African continent and Barbados.

Of the 12 loci that reached the genome-wide significance in the study, eight showed a significantly different association according to estrogen receptor (ER) status, including five loci that were overrepresented in ER-positive breast cancer and three loci with a stronger association with ER-negative breast cancer.

Across the subset of 2,860 women in the study who had TNBC, the researchers found that more than 15 percent showed particularly high genetic risk of the condition, carrying at least six TNBC-related alleles at sites linked to the subtype in the past. These women are 4.2 times more likely to be diagnosed with TNBC than those who carry none or only one of the variants. TNBC is more likely to develop in women of West African ancestry than women of other ethnic backgrounds.

Of particular interest, the team identified one locus (rs76664032 at 2q14.2) that was strongly associated with the risk of TNBC. In this study, the risk allele of this variant was very common, approximately 81 percent, with “a strong association rarely observed in GWAS of cancers,” according to the researchers. Their study found that two other loci—rs10069690 at 5p15.33 and rs12974508 at 19p13.11—also showed a strong association with TNBC at genome-wide significance. While these two loci were associated with TNBC risk among European women, the association was much weaker.

The study’s polygenic risk score (PRS) showed an area 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,” the authors write, concluding that the study represents a substantial step forward in reducing the inclusion disparities in cancer susceptibility studies.

The data for the study was collected from researchers across more than 15 institutions as part of the African Ancestry Breast Cancer Genetic (AABCG) consortium. “Data put together in this consortium have been and will continue to be used by researchers around the world to address significant questions related to breast cancer etiology and genetics,” said the study’s corresponding author Wei Zheng, MD, PhD, of the Vanderbilt Epidemiology Center.

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