February 16, 2023

Breast cancer genetics: new insights

Largest genetic study of breast cancer to date identifies 222 genetic risk loci, 137 genes and multiple signaling pathways associated with risk, providing important new insights.

Genetic factors play a significant role in both inherited and sporadic breast cancer — the most commonly diagnosed cancer in women worldwide. Genome-wide association studies have identified genetic variants in about 200 loci, but these studies have included mostly women of European ancestry. 

Now, Damon Jia, PhD, MPH, Wei Zheng, MD, PhD, MPH, and colleagues report the largest genetic study of breast cancer to date using data from 386,000 women of Asian and European ancestry. The researchers conducted genome- and transcriptome-wide association studies and pathway analyses. They identified 222 genetic risk loci, 137 genes and multiple signaling pathways associated with breast cancer risk. Genetic risk variants differed based on ancestry and cancer estrogen receptor status. 

The findings, reported in The American Journal of Human Genetics, provide important new insights into the genetics and biology of breast cancer and identify potential therapeutic targets. Future studies that increase the number of non-European individuals will be valuable to fully uncover the genetic basis of breast cancer, the researchers note.

Jia and Jie Ping, PhD, in the Division of Epidemiology at Vanderbilt University Medical Center are co-first authors of the study. Other VUMC authors include Yaohua Yang, PhD, Qiuyin Cai, MD, PhD, Xingyi Guo, PhD, Bingshan Li, PhD, Ran Tao, PhD, Xiao-Ou Shu, MD, PhD, MPH, and Jirong Long, PhD. 

The research was supported in part by the National Institutes of Health (grants CA235553, CA202981, CA124558, CA148667, CA158473, CA064277, CA070867, CA182910, CA118229 CA092585, CA122756, CA137013), Department of Defense Idea Awards, and Ingram Professor and Anne Potter Wilson Chair and Research Reward funds.