Scientists have linked 110 genes to an increased risk of breast cancer in the most comprehensive study ever to unpick the genetics of the disease.
Their study used a pioneering genetic technique to analyse maps of DNA regions linked to an inherited risk of breast cancer and identify the actual genes involved in raising a woman's risk.
Researchers also linked 32 of the new genes to the length of time women survived breast cancer - suggesting these could be important in the development of the disease and potential targets for future treatments.
Scientists at The Institute of Cancer Research, London, looked in detail at 63 areas of the genome that had previously been associated with the risk of breast cancer by mapping studies.
Finding the genes responsible for the increased risk is not straightforward because small sequences of DNA can interact with completely different parts of the genome through a strange phenomenon known as 'DNA looping'.
But the researchers, funded by Breast Cancer Now, used a technique they developed called Capture Hi-C to study interactions between different regions of the genome.
The study - published today (Monday) in Nature Communications - uncovered which specific genes were involved and how that might increase a woman's risk of developing breast cancer.
The team at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR) found that some of the 63 regions of the genome were physically interacting with genes more than a million letters of DNA code away.
They were able to identify 110 new genes that could potentially be causing an increased risk of breast cancer across 33 of the regions they studied. In the remaining 30 areas, they were unable to find any specific genes.
One third of the target genes for which they had patient data - 32 out of 97 - were also linked to survival in women with oestrogen receptor-positive breast cancer, suggesting they play an important role in the disease.
In the future, testing for these genes could help pick out women who are most at risk of developing the disease - or they could be explored as targets for new drugs.
Scientists at the ICR - a research institute and charity - studied DNA loops in cells from four different types of breast cancer and normal, healthy cells to find out which genes were consistently involved in looping interactions.
Most of the 110 genes found in the study had not been linked to breast cancer risk before, and further work will be needed to determine the extent of their role in the disease.
One of these, called FADD, has previously been linked to head and neck cancer and lung cancer and could be a promising target for new cancer therapies.
Previous large-scale genetics studies have implicated 14 of the 110 genes as playing a role in breast cancer risk, such as the oestrogen receptor gene ESR1, showing that Capture Hi-C is an effective tool for picking up risk genes.
Dr Olivia Fletcher, Team Leader in Functional Genetic Epidemiology at The Institute of Cancer Research, London, said: "Our study took the high-level maps of breast cancer risk regions and used them to pull out specific genes that seem to be associated with the disease.
"We studied how DNA forms loops to allow physical interactions between a DNA sequence in one part of the genome and a risk gene in another.
"Identifying these new genes will help us to understand in much greater detail the genetics of breast cancer risk. Ultimately, our study could pave the way for new genetic tests to predict a woman's risk, or new types of targeted treatment."
Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, which funded the study, said: "These are really important findings. We urgently need to unravel how the genetic changes in the building blocks of our DNA influence a woman's risk of breast cancer, and this study adds another vital piece to this jigsaw.
"More women are now being diagnosed with breast cancer than ever before, and these crucial findings could ultimately help us more accurately predict who is most at risk and develop new targeted treatments.
"Many of these genes have been relatively undocumented to date and we now hope further research will untangle their exact role in breast cancer risk, and how we could use them to stop more women developing the disease."
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said: "Large-scale genomic studies have been instrumental in associating areas of our DNA with an increased risk of breast cancer. This study brings these regions of DNA into sharper focus, uncovering a treasure trove of genes that can now be investigated in more detail.
"The ways in which particular genes influence cancer risk are highly complex. In the future, a better understanding of the genes identified in this study could lead to the discovery of new targeted drugs, or new strategies to improve diagnosis or prevention of the disease."
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Notes to editors
For more information please contact Sarah Wells in the ICR press office on 020 7153 5582 or sarah.wells@icr.ac.uk. For enquiries out of hours, please call 07595 963 613.
The Institute of Cancer Research, London, is one of the world's most influential cancer research organisations.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four centres for cancer research and treatment globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
A college of the University of London, the ICR is the UK's top-ranked academic institution for research quality, and provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk.
About Breast Cancer Now:
* Breast Cancer Now is the UK's largest breast cancer charity.
* Breast Cancer Now's ambition is that by 2050 everyone who develops breast cancer will live. The charity is determined to stop women dying from the disease, working in a new, collaborative way and bringing together all those affected by the disease to fund research, share knowledge and find answers.
* Breast Cancer Now's world-class research is focused entirely on breast cancer. The charity supports nearly 450 of the world's brightest researchers at 29 locations across the UK and Ireland. Together, they're working to discover how to prevent breast cancer, how to detect it earlier and how to treat it effectively at every stage so we can stop the disease taking lives.
* Breast cancer is still the most common cancer in the UK. Nearly 700,000 people living in the UK have experienced a diagnosis and one in eight women will face it in their lifetime. This year alone, more than 50,000 women will be told they have the disease.
* The UK still has one of the lowest breast cancer survival rates in Western Europe and this year alone around 11,500 women will lose their lives. It's time to act.
* Breast Cancer Now launched in June 2015, created by the merger of leading research charities Breast Cancer Campaign and Breakthrough Breast Cancer.
* For more information on Breast Cancer Now's work, visit breastcancernow.org or follow us on Twitter or on Facebook. Breast Cancer Now thanks M&S for their generous support of this research.
Journal
Nature Communications