By Lisa Winter                  February 23, 2015 

The two genes most commonly implicated with increased risk for breast cancer are BRCA 1 and BRCA 2, though there may be two other genes doctors will be checking for in the future. A new paper published in Human Molecular Genetics describes a massive international collaboration led by The Institute of Cancer Research in London on two new genetic variants that are linked to an increased risk for breast cancer.
The study analyzed genetic data from 100,000 women of various ethnic descent, roughly 50,000 of whom had been diagnosed with breast cancer. Ultimately, they discovered two genetic variants on chromosome 9 which affect the function of KLF4, a transcription factor that helps regulate the growth and replication of cells.
"Our study zoomed in on an area of our genome that we knew was linked to breast cancer risk, and has identified two new genetic variants that add significantly to our knowledge about the genetic causes of the disease,” said lead author Nick Orr from The Institute of Cancer Research in a press release
"The variants we identified are specifically associated with the most common, estrogen receptor positive, form of breast cancer. The more genetic risk factors for breast cancer we discover, of which there are currently more than 80, the more accurately we will be able predict who is at risk of getting the disease. Ultimately this will be vital for designing preventative strategies against breast cancer.”
Certain mutations on BRCA1/2 are associated with over a 70% chance of developing breast cancer over the course of one’s life. The newly-discovered mutations described in the current paper are not quite as high. The mutation at the location rs10816625 corresponded to a 12% increased risk, while a mutation at the site rs13294895 represented a 9% increased risk for certain forms of the disease. When dealing with estrogen receptor positive breast cancer, the risk increased to 14% and 11%, respectively. 
”The two new variants uncovered by this study could be factored into potential future screening tools for breast cancer that incorporate all known genetic risk factors for the disease,” added Paul Workman, CEO of The Institute of Cancer Research. “They also provide important clues to the genetic causes of the most common form of breast cancer and potential leads for the discovery of new treatments.”
Though these additional risks might sound minimal by comparison, genetics is not the sole cause of disease. A number of environmental and lifestyle factors are also involved, but understanding all possible genetic factors could give physicians another avenue in which to screen patients, allowing potential treatment to begin sooner.
"Thanks to modern technology we're building an increasingly detailed picture of the small variations in DNA that can influence a woman's risk of breast cancer,” explained Emma Smith of Cancer Research UK. “The next challenges are understanding the biology underpinning their effects, so we can use this information to predict individual risk more accurately, improve screening and find better ways to treat and prevent breast cancer.”