Research led by Vanderbilt University Medical Center investigators delved into data from genome-wide association studies of 414,746 females in the study, which was published in Nature Genetics. They identified 332 independent association signals for breast cancer risk, including 131 signals not previously reported.

By analyzing large amounts of genomic and functional genomic data, the study identified 195 candidate breast cancer susceptibility genes.

Many of these genes are located in multiple cancer-related signaling pathways, including several major pathways that are altered in breast cancer cells. These results suggest that constitutional alterations of genes previously linked to breast tumorigenesis may also contribute significantly to genetic susceptibility to breast cancer.   

The study represents the largest multiancestry GWAS and fine-mapping analyses conducted to date for breast cancer risk with African-ancestry females included. The work is part of an ongoing initiative at VUMC to broaden the knowledge about breast cancer risk factors for more diverse populations, particularly females of African ancestry for which data has been limited.  

Mutiancestry fine-mapping is informative to identify potential causal variants and genes because of the diversity of genome architectures across populations, said Guochong Jia, PhD, MPH, the study’s lead author.  

Jia is a postdoctoral fellow on the research team led by Wei Zheng, MD, PhD, MPH, the Anne Potter Wilson Professor of Medicine, associate director of Population Science Research at Vanderbilt-Ingram Cancer Center and director of the Division of Epidemiology.  

Studies like this are only possible through close collaborations with large numbers of scientists around the world. The study highlights the value of conducting genetic analyses including multiancestry populations, said Zheng, the report’s senior and corresponding author.  

The study included 133,384 females of European ancestry, 21,319 females of Asian ancestry and 18,034 females of African ancestry who were diagnosed with breast cancer.

For comparisons, the study also included control groups for each ancestry population. The analyses were conducted for the risk of overall breast cancer, estrogen receptor-positive breast cancer, estrogen receptor-negative breast cancer and triple-negative breast cancer.   

Souce : https://news.vumc.org/2025/01/15/study-in-multiancestry-populations-uncovers-new-insights-into-breast-cancer-genetics/