72 new genetic markers for breast cancer identified in global study

Researchers from 300 different institutions have collaborated on the world’s biggest ever genetic study of breast cancer, which collated and analysed data from 275,000 women across the globe — and discovered 72 new genetic markers for the disease in the process.

Although 105 genetic regions have previously been associated with breast cancer, much of the genetic contribution to risk remains unknown. Now, scientists co-led by Australia’s own QIMR Berghofer Medical Research Institute have used a new targeted genotyping array to compare the genomes of women with and without breast cancer.

The coordinator of QIMR Berghofer’s Genetics and Computational Biology Department, Professor Georgia Chenevix-Trench, said the study found 65 genetic variants that predispose women to overall risk of breast cancer. Together, these account for 18% of the familial relative risk of developing breast cancer. The results were published in the journal Nature.

According to QIMR Berghofer senior researcher Dr Jonathan Beesley, the results could enable scientists to predict which neighbouring genes the risk variants might act on. He said, “We were able to show for the first time that these risk genes are often the same ones that are mutated during the development of breast tumours, which tells us much more then we knew previously about the genetic mechanisms that may cause breast cancer.

“We think that this ability to pinpoint the genes associated with risk of breast cancer will eventually enable us to develop more effective screening interventions and even risk-reduction medications and treatments.”

Meanwhile, in the journal Nature Genetics, the scientists published research into a particular subset of breast cancer, comparing the genomes of women with oestrogen receptor (ER)-negative tumours, carriers of the BRCA1 susceptibility gene and control subjects. Unlike oestrogen-receptor positive breast cancer, which is fed by the hormone oestrogen, oestrogen-receptor negative breast cancer responds to other mechanisms.

Seven genetic variants were found to predispose women specifically to ER-negative breast cancer, which often leads to poorer health outcomes because it does not respond to drugs like tamoxifen. The researchers also noted a strong link between the breast cancer risk for BRCA1 mutation carriers and the risk of ER-negative breast cancer in the general population.

Professor Chenevix-Trench said the inherited component of breast cancer risk is due to a combination of rare variants in genes such as BRCA1 and BRCA2 that indicate a high risk of the disease, and genetic variants that confer only a small risk, as identified in the latest research.

“This work helps us to understand why some women are more at risk of developing breast cancer than others and what genetic markers we should be looking for in order to assess that risk,” Professor Chenevix-Trench said.

“We know that breast cancer is caused by complex interactions between these genetic variants and our environment, but these newly discovered markers bring the number of known variants associated with breast cancer to around 180.

“Our hope is that in future we will be able to test for these genetic variants in order to inform preventative approaches and treatment for women who may be at a higher risk of breast cancer.”