Global Breast Cancer Study Reveals 72 New Mutations

The total number of known gene variants associated with breast cancer is now nearly 180, according to a recent study. In addition, newly identified variants may help identify a small proportion of women who are three times more likely to develop breast cancer. 

Researchers at the University of Cambridge report in the journals Nature and Nature Genetics that 65 of the 180 gene variants are common variants that predispose to breast cancer and an additional 7 predispose specifically to estrogen receptor (ER)–negative breast cancer, the subset of cases that do not respond to hormonal therapies such as tamoxifen.

“We identified 72 new common variants associated with an increased risk of breast cancer, bringing the total number to approximately 180. Some of these are specific to ER-negative disease. We found that the majority of variants fell in regions that regulate nearby genes. In the majority of cases, we could predict a target gene. We showed that these genes overlapped with those known to be mutated in breast tumors,” said study investigator Doug Easton, Professor of Genetic Epidemiology at the Centre for Cancer Genetic Epidemiology at University of Cambridge, Cambridge, England.

The findings are from the OncoArray Consortium, an endeavor involving 550 researchers from around 300 different institutions on 6 continents. In total, they analyzed genetic data from 275,000 women, of whom 146,000 had been diagnosed with breast cancer. The analysis included 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers.

By combining epidemiologic data with other data from breast tissue, the researchers were able to make plausible predictions of the target genes in a large majority of cases. Easton said risk variants can be used to predict overall risk. In addition, these numbers can be combined into a risk score that can be used to stratify women. “This can be used to tailor prevention, in particular targeting screening, and potentially risk-reducing medication (tamoxifen or raloxifene) for those women who are most likely to benefit. It can also identify those women in whom new forms of early detection can be studied,” Easton told OncoTherapy Network.

Easton said by identifying these target genes, it may be possible to better define the pathways and mechanisms underlying breast cancer susceptibility. He said these targets may prove to be potential new therapeutic targets. “Tests based on these findings will likely soon be commonplace,” said Easton.