A worldwide study of the DNA of 100,000 women has discovered two new genetic variants associated with an increased risk of breast cancer. The genetic variants are specifically linked to the most common form of breast cancer, estrogen-receptor positive (ER+), and provide important insights into how the disease develops.

Scientists believe screening women for all the genetic variants so far identified could eventually pick out those at highest risk of breast cancer and improve strategies for preventing the disease.

The study was led by scientists at The Institute of Cancer Research, London, United Kingdom, and was published in Human Molecular Genetics (2015; doi:10.1136/bmj.h653). It analyzed the DNA of approximately 86,000, 12,000, and 2,000 women of European, Asian, and African ancestries, respectively; approximately half of the women had breast cancer.

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The study’s identification of two new genetic risk factors for breast cancer provides important clues about the causes of the disease. It implicated a gene called KLF4, which is thought to help control the way cells grow and divide.

The research was funded by a range of organizations including Cancer Research UK, Breakthrough Breast Cancer, and the European Union.

Researchers were looking for one-letter differences in DNA code that were more likely to be found in women with breast cancer than those without the disease, using a state-of-the-art genetic technique called fine mapping. They focused on a recently identified hotspot for genetic causes of breast cancer on chromosome 9.

Women with the first genetic variant identified, rs10816625, were 12% more likely to develop breast cancer than women without, and those with the second variant, rs13294895, had a 9% increased risk.

The increases in risk were slightly higher, at 14% and 11%, respectively, for ER+ breast cancer, but there was no association with ER negative forms of the disease.

The genetic variants are thought to help control the activity of KLF4, despite lying a long distance away from that gene.

Both were associated with increased risk in European women but only one of them, rs10816625, in women of Asian ancestry.

“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 study leader Nick Orr, PhD, team leader in Complex Trait Genetics at The Institute of Cancer Research, London.

“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.”