Scientists identify 72 new genetic variants contributing to breast cancer risk

Seventy-two new genetic variants that contribute to the risk of developing breast cancer have been identified by an extensive, international team of researchers. The findings were reported in the journals Nature and Nature Genetics. Genetic studies pave way for understanding the pathogenesis of breast cancer.

Breast cancer is caused by complex interactions between a large number of genetic variants and our environment. The inherited component of breast cancer risk is due to a combination of rare variants in genes such as BRCA1 and BRCA2 that confer a high risk of the disease, and many commoner genetic variants that each confer only a small risk. The newly identified risk regions nearly double the number that are already known, thereby bringing the number of known common variants associated with breast cancer to around 180. The findings help understand why some women are predisposed to breast cancer, and which genes and mechanisms are involved. The studies showed for the first time that these genes are often the same as those that are altered in breast tumours – when a tumour develops, the DNA within the cancer cells themselves mutates.

Around 70% of all cases of breast cancer are oestrogen-receptor positive, meaning that the cancer cells have a particular protein (known as a receptor) that responds to the female sex hormone oestrogen, enabling the tumour to grow. However, not all cancer cells carry this receptor – these are known as oestrogen-receptor negative. The studies identified genetic regions specifically associated with either oestrogen-receptor positive or oestrogen receptor negative breast cancer, underscoring the fact that these are biologically distinct cancers that develop differently.

The researchers estimated that one percent of women have a risk of breast cancer that is more than 3 times greater than the population at large.  Larger differences in risk can be found if the genetic variants are combined with other hormonal and lifestyle factors that influence breast cancer risk. The researchers believe these differences may be sufficient to change practice, such as in how women at different risks are screened. Using data from genomic studies, combined with information on other known risk factors, will allow better breast cancer risk assessment, therefore helping to identify a small but meaningful proportion of women at high risk of breast cancer.

The findings are the result of work by the OncoArray Consortium, a huge endeavour involving 550 researchers from around 300 different institutions in six continents. In total, they analysed genetic data from 275,000 women, of whom 146,000 had been diagnosed with breast cancer.

The Finnish collaborators in the OncoArray Consortium are the University of Eastern Finland, the University of Helsinki, and the University of Oulu.

Michailidou, K et al. Association analysis identifies 65 new breast cancer risk loci. Nature; 23 Oct 2017; DOI: 10.1038/nature24284

Milne, RL et al. Identification of ten variants associated with risk of estrogen receptor negative breast cancer. Nature Genetics; 23 Oct 2017; DOI: 10.1038/ng.3785

University of Eastern Finland press release
University of Cambridge press release

Last updated: 27.10.2017