One study focused on the 30 percent of resistant breast cancer which do not respond to conventional hormone treatment, and identified ten new variants.
'These findings add significantly to our understanding of the inherited basis of breast cancer,' said Dr Doug Easton of the University of Cambridge, one of the lead investigators. 'As well as identifying new genetic variants, we have also confirmed many that we had previously suspected. There are some clear patterns in the genetic variants that should help us understand why some women are predisposed to breast cancer, and which genes and mechanisms are involved.'
The research was carried out by the OncoArray consortium, which includes more than 550 researchers at 300 research facilities worldwide.
First-degree relatives of breast cancer patients show twice the risk of breast cancer, compared to women without a family history of the disease. However, while there are 180 known genetic variants which increase risk, most of the genetic basis is unknown.
The scientists performed two GWAS studies of over 275,000 breast cancer and control patients of European or East Asian ancestry, using a chip called the OncoArray, and combined their findings with data from past studies. The OncoArray chip identifies single nucleotide polymorphisms (SNPs) across the genome, but particularly in regions thought to be related to cancer.
In the second study, published in Nature Genetics, the scientists focused on hormone-resistant breast cancer. They identified ten new variants which were linked to 1.5 percent of heritable risk, including three variants also identified in the Nature study.
Although a few mutations, such as those found in the BRCA1 or BRCA2 genes, can greatly increase the risk of breast cancer, the variants identified in the studies are common and some are carried by over 50 percent of women. Each variant confers only a small amount of risk, but combine to increase overall risk. Most did not code for proteins, but were in regions involved in regulation of genetic expression.
The team say their findings could provide new avenues of research for the genetic basis of breast cancer, particularly for hormone therapy-resistant disease. In combination with other factors influencing risk, their data could also help identify women at a high risk of breast cancer, who may benefit from tailored treatment.
'These women may benefit from more intensive screening, starting at a younger age, or using more sensitive screening techniques, allowing early detection and prevention of the disease,' said team member Professor Jacques Simard of Laval University in Quebec, Canada.