Genetics & Genomics

February 28, 2013

Potent genetic risk factor for breast cancer identified

Researchers at Vanderbilt University have found a powerful new genetic risk factor for breast cancer.


Researchers at Vanderbilt University have found a powerful new genetic risk factor for breast cancer.

Using data from population-based studies of women in Shanghai, China, Jirong Long, Ph.D., assistant professor of Medicine, and colleagues discovered a deletion in a cluster of genes, called APOBEC3 genes, that are known to trigger DNA mutation and which have previously been implicated in cancer.

Jirong Long, Ph.D.

If a woman has a deletion in one of the two sets of genes she inherits from her parents, her risk of breast cancer increases by 31 percent. If the deletion is present in both sets of genes, her risk increases by 76 percent.

“This is the first copy number variation or CNV identified for breast cancer and is one of the strongest common genetic risk variants identified so far for breast cancer,” the researchers reported in the Journal of the National Cancer Institute.

This newly identified genetic marker, in combination with other markers, might be helpful to predict the risk of breast cancer. However, the utility of these markers in risk prediction should be carefully evaluated before any recommendation for genetic testing can be made, the researchers said.

CNVs are deletions or duplications of specific sections of DNA. They are an important source of human genetic variation, and have been associated with several other complex diseases, including HIV/AIDS, psoriasis, Crohn’s disease and autism.

Long and her colleagues identified the risk factor by conducting a genome-wide association study, or GWAS. That is a method of screening the genomes of individuals for variations, in this case CNVs, and then determining which variations are associated with increased breast cancer risk.

First they conducted the GWAS in more than 4,000 women who have participated in various cancer studies in Shanghai; then replicated the result in 8,500 more.

Half of the women had been diagnosed with breast cancer and the others served as controls.

The studies, which include the Shanghai Women’s Health Study and the Shanghai Breast Cancer Study, date back to the mid-1990s, and are directed by Wei Zheng, M.D., Ph.D., and Xiao-Ou Shu, M.D., Ph.D., MPH., co-authors of Long’s paper.

The study was conducted in collaboration with researchers at the Shanghai Center for Disease Control and Prevention and the Shanghai Cancer Institute. Other Vanderbilt authors on the paper are Ryan Delahanty, Ph.D., Guoliang Li, Ph.D., Qiuyin Cai, M.D., Ph.D., and Chun Li, Ph.D.

The research was supported in part by National Institutes of Health grants CA137013, CA148667, CA124558, CA064277, CA070867, CA118229, CA092585 and CA122756.